Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

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Erika Suzuki

Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

A Phase I study of intermittently dosed vorinostat in combination with bortezomib in patients with advanced solid tumors.

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Deming, Dustin A; Ninan, Jacob; Bailey, Howard H; Kolesar, Jill M; Eickhoff, Jens; Reid, Joel M; Ames, Matthew M; McGovern, Renee M; Alberti, Dona; Marnocha, Rebecca; Espinoza-Delgado, Igor; Wright, John; Wilding, George; Schelman, William R

2014-04-01

Accumulating evidence shows evidence of efficacy with the combination of vorinostat and bortezomib in solid tumors. We previously examined a once-daily continuous dosing schedule of vorinostat in combination with bortezomib which was well tolerated in cycles 1 and 2; however, there was concern regarding the tolerability through multiple cycles. This study was conducted to evaluate an intermittent dosing schedule of vorinostat with bortezomib. Vorinostat was initially administered orally twice daily on days 1-14 with bortezomib IV on days 1, 4, 8, and 11 of a 21 day cycle. Two DLTs (elevated ALT and fatigue) were observed at dose level 1, thus the protocol was amended to administer vorinostat intermittently twice daily on days 1-4 and 8-11. 29 patients were enrolled; 13 men and 16 women. Common cancer types included sarcoma, pancreatic, colorectal, GIST, and breast. The most common Grade 3-4 toxicities at any dose level included thrombocytopenia, fatigue, increased ALT, elevated INR, and diarrhea. DLTs in the intermittent dosing scheduled included thrombocytopenia and fatigue. The Cmax and AUC for the intermittent dosing regimen were similar to those observed in the daily dosing. In this heavily pretreated population, stable disease was observed in patients with sarcoma, colorectal adenocarcinoma and GIST. The MTD was established at vorinostat 300 mg BID on days 1-4 and 8-11 and bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, and 11 of a 21 day cycle. Tolerability was not improved with the intermittent dosing schedule of vorinostat when compared to continuous dosing.

Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials.

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Mateos, Maria-Victoria; Oriol, Albert; Martínez-López, Joaquín; Teruel, Ana-Isabel; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Esseltine, Dixie-Lee; Cakana, Andrew; Pei, Lixia; van de Velde, Helgi; Miguel, Jesus San

2016-12-01

Bortezomib-melphalan-prednisone (VMP) is a standard-of-care for previously untreated, transplant-ineligible multiple myeloma (MM). Here, we compared outcomes between VMP regimens in the VISTA trial (9-cycle VMP schedule, including 4 cycles of twice weekly bortezomib) and the PETHEMA/GEM05 trial (less intensive 6-cycle VMP schedule with 1 cycle of twice weekly and 5 cycles of weekly bortezomib, then bortezomib-based maintenance). A total of 113 patient pairs matched by propensity score (estimated using logistic regression and incorporating eight exposure/outcome-related parameters) were included in this retrospective analysis. Median cumulative bortezomib dose was higher in PETHEMA/GEM05 than VISTA (49.6 vs 37.0 mg/m 2 ); median dose intensity was lower (2.0 vs 5.1 mg/m 2 /month). Median progression-free survival (PFS) and time-to-progression (TTP) were significantly longer in PETHEMA/GEM05 than VISTA (PFS, 30.5 vs 20.0 months, p = 0.0265; TTP, 33.8 vs 24.2 months, p = 0.0049) after a median follow-up of 77.2 and 26.0 months, respectively. Median overall survival (OS) was similar (61.3 vs 61.0 months, p = 0.6528; median follow-up, 77.6 vs 60.1 months). Post-induction complete response rate was lower in PETHEMA/GEM05 than VISTA (19 vs 31 %; p = 0.03318); on-study (including maintenance) rate was similar (30 vs 31 %; p = 0.89437). This analysis suggests that the less-intensive PETHEMA/GEM05 VMP regimen plus maintenance may improve PFS and TTP, but not OS, compared with the VISTA VMP regimen. NCT00111319, NCT00443235.

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial

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Gimsing, P; Hjertner, Ø; Abildgaard, N

2015-01-01

, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared......Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib...... included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT...

Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study.

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Dimopoulos, Meletios; Siegel, David S; Lonial, Sagar; Qi, Junyuan; Hajek, Roman; Facon, Thierry; Rosinol, Laura; Williams, Catherine; Blacklock, Hilary; Goldschmidt, Hartmut; Hungria, Vania; Spencer, Andrew; Palumbo, Antonio; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Sun, Linda; Vuocolo, Scott; Anderson, Kenneth C

2013-10-01

We aimed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma. In our randomised, double-blind, placebo-controlled, phase 3 trial, we enrolled adults (≥18 years) at 174 university hospitals in 31 countries worldwide. Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment (one to three regimens) but were currently progressing, ECOG performance statuses of 2 or less, and no continuing toxic effects from previous treatment. We excluded patients with known resistance to bortezomib. We randomly allocated patients (1:1) using an interactive voice response system to receive 21 day cycles of bortezomib (1·3 mg/m(2) intravenously on days 1, 4, 8, and 11) in combination with oral vorinostat (400 mg) or matching placebo once-daily on days 1-14. We stratified patients by baseline tumour stage (International Staging System stage 1 or stage ≥2), previous bone-marrow transplantation (yes or no), and number of previous regimens (1 or ≥2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed adverse events in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number 00773747. Between Dec 24, 2008, and Sept 8, 2011, we randomly allocated 317 eligible patients to the vorinostat group (315 of whom received at least one dose) and 320 to the placebo group (all of whom received at least one dose). Median PFS was 7·63 months (95% CI 6·87-8·40) in the vorinostat group and 6·83 months (5·67-7·73) in the placebo group (hazard ratio [HR] 0·77, 95% CI 0·64-0·94; p=0·0100). 312 (99%) of 315 patients in the vorinostat group and 315 (98%) of 320 patients in the placebo group had adverse events (300 [95%] adverse events in the vorinostat group and 282 [88%] in the control group were regarded as related to treatment). The most

Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline.

Science.gov (United States)

Reece, D; Imrie, K; Stevens, A; Smith, C A

2006-10-01

used in major trials. Some of those details are provided here for informational purposes. Bortezomib 1.3,g/m(2) is given as a rapid intravenous bolus over 3-5 seconds on days 1, 4, 8, and 11 of a 21-day cycle; a minimum of 72 hours between doses is required to allow for recovery of normal proteasome function. Vital signs should be checked before and after each dose. A complete blood count is recommended before each dose, with blood chemistries (including electrolyte and creatinine levels) monitored at a minimum on days 1 and 8 of each cycle. The dose of bortezomib should be reduced or held immediately upon development of painful neuropathy, as described in the product monograph; dose modification may also be required for peripheral sensory neuropathy without pain or for other toxicities. Most toxicities are reversible if dose modification guidelines are followed. RESPONSE TO TREATMENT: Responses are usually apparent by 6 weeks (2 cycles). For patients achieving complete remission (determined by negative electrophoresis and immunofixation), bortezomib should be given for 2 additional cycles beyond the date of confirmed complete remission. In patients with progressive disease after 2 cycles or stable disease after 4 cycles, dexamethasone added to the bortezomib regimen (20 mg by mouth the day of and the day after each bortezomib dose) may produce an objective response. Bortezomib (with or without dexamethasone) should be continued in patients showing benefit from therapy (excluding those in complete remission) unless disease progression or significant toxicity is observed. Therapy should be discontinued in patients who do not respond to bortezomib alone if disease progression is seen within 2 cycles of the addition of dexamethasone. The Hematology dsg recognizes that thalidomide is an active agent in multiple myeloma patients who have relapsed after autologous stem-cell transplantation or who are refractory to alkylating agent-based chemotherapy. To date, no reported

Bortezomib interactions with chemotherapy agents in acute leukemia in vitro.

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Horton, Terzah M; Gannavarapu, Anurhadha; Blaney, Susan M; D'Argenio, David Z; Plon, Sharon E; Berg, Stacey L

2006-07-01

Although there is effective chemotherapy for many patients with leukemia, 20% of children and up to 65% of adults relapse. Novel therapies are needed to treat these patients. Leukemia cells are very sensitive to the proteasome inhibitor bortezomib (VELCADE(R), PS-341), which enhances the in vitro cytotoxic effects of dexamethasone and doxorubicin in multiple myeloma. To determine if bortezomib enhances the cytotoxicity of agents used in leukemia, we employed an in vitro tetrazolium-based colorimetric assay (MTT) to evaluate the cytotoxic effects of bortezomib alone and in combination with dexamethasone, vincristine, doxorubicin, cytarabine, asparaginase, geldanamycin, trichostatin A, and the bcl-2 inhibitor HA14.1. We demonstrated that primary leukemia lymphoblasts and leukemia cell lines are sensitive to bortezomib, with an average IC(50) of 12 nM. Qualitative and quantitative bortezomib-drug interactions were evaluated using the universal response surface approach (URSA). Bortezomib was synergistic with dexamethasone in dexamethasone-sensitive leukemia cells, and additive with vincristine, asparaginase, cytarabine, and doxorubicin. The anti-leukemic activity of bortezomib was also additive with geldanamycin and HA14.1, and additive or synergistic with trichostatin A. These results were compared to analysis using the median-dose effect method, which generated complex drug interactions due to differences in dose-response curve sigmoidicities. These data suggest bortezomib could potentiate the cytotoxic effects of combination chemotherapy in patients with leukemia.

Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib.

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Julia S Gelman

Full Text Available Bortezomib is an antitumor drug that competitively inhibits proteasome beta-1 and beta-5 subunits. While the impact of bortezomib on protein stability is known, the effect of this drug on intracellular peptides has not been previously explored. A quantitative peptidomics technique was used to examine the effect of treating human embryonic kidney 293T (HEK293T cells with 5-500 nM bortezomib for various lengths of time (30 minutes to 16 hours, and human neuroblastoma SH-SY5Y cells with 500 nM bortezomib for 1 hour. Although bortezomib treatment decreased the levels of some intracellular peptides, the majority of peptides were increased by 50-500 nM bortezomib. Peptides requiring cleavage at acidic and hydrophobic sites, which involve beta-1 and -5 proteasome subunits, were among those elevated by bortezomib. In contrast, the proteasome inhibitor epoxomicin caused a decrease in the levels of many of these peptides. Although bortezomib can induce autophagy under certain conditions, the rapid bortezomib-mediated increase in peptide levels did not correlate with the induction of autophagy. Taken together, the present data indicate that bortezomib alters the balance of intracellular peptides, which may contribute to the biological effects of this drug.

Bortezomib in the management of multiple myeloma

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Jacob P Laubach

2009-09-01

Full Text Available Jacob P Laubach, Constantine S Mitsiades, Teru Hideshima, Robert Schlossman, Dharminder Chauhan, Nikhil Munshi, Irene Ghobrial, Nicole Carreau, Kenneth C Anderson, Paul G RichardsonDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USAAbstract: Multiple myeloma (MM is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molecule proteasome inhibitor bortezomib occurred as a result of these efforts. This review focuses on the rationale for bortezomib therapy in the treatment of patients with newly diagnosed and relapsed MM, important treatment-related side effects, and future directions for use of bortezomib and other, emerging proteasome inhibitors.Keywords: multiple myeloma, bortezomib, stem cell transplantation, peripheral neuropathy

Curcumin Enhances Bortezomib Treatment of Myeloma by Inhibiting ...

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Keywords: Curcumin, Bortezomib, Myeloma cells, Cell growth, Apoptosis, Heat shock protein 90. Tropical Journal of ... strategies have been employed, including traditional chemotherapy, ... particularly on account of bortezomib's adverse effects such as nausea, diarrhea, ... (MM.1R), which were kindly provided by Dr.

Chalazia development in multiple myeloma: a new complication associated with bortezomib therapy

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Charles Yun

2015-06-01

Full Text Available Multiple myeloma (MM is a neoplasm of plasma cells within the bone marrow. A major impact on improving survival in MM has been the use of the boronic acid-derived proteasome inhibitor bortezomib, a first-in-class selective inhibitor of the 26S proteasome. Ocular side effects of bortezomib are rare. In this report, we present 2 patients with active MM in whom persistent chalazia became a therapy-interfering complication of treatment with bortezomib. Both patients had relapsed ISS III B kappa light chain myeloma, and they were responding to treatment with bortezomib until chalazia − which caused intolerable discomfort − started. In both patients discontinuation of bortezomib was necessary for chalazia to heal, and restarting of bortezomib was associated with relapse of chalazia.

Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation

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Pérez-Galán, Patricia; Mora-Jensen, Helena; Weniger, Marc A

2011-01-01

bortezomib-resistant MCL cell lines and primary tumor cells from MCL patients with inferior clinical response to bortezomib also expressed plasmacytic features. Knockdown of IRF4 was toxic for the subset of MCL cells with plasmacytic differentiation, but only slightly sensitized cells to bortezomib. We...

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

NARCIS (Netherlands)

P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

2005-01-01

textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats

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Shota Yamamoto

2015-09-01

Full Text Available Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN, because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg, pregabalin (3 mg/kg, duloxetine (30 mg/kg or mexiletine (100 mg/kg, but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.

Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

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Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

2013-01-01

The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

Concurrent whole brain radiotherapy and bortezomib for brain metastasis

International Nuclear Information System (INIS)

Lao, Christopher D; Hamstra, Daniel; Lawrence, Theodore; Hayman, James; Redman, Bruce G; Friedman, Judah; Tsien, Christina I; Normolle, Daniel P; Chapman, Christopher; Cao, Yue; Lee, Oliver; Schipper, Matt; Van Poznak, Catherine

2013-01-01

Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis. A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m 2 ) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects. Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m 2 /dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023). Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment

Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

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Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

2016-02-01

Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

Bortezomib-based treatment of acute antibody-mediated rejection: a case report.

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Wang, Q; Li, X L; Xu, X G; Shi, B Y; Zhang, Z M; Li, Z L; Han, Y; Zhou, W Q; Chen, C Q; Cai, M; Zhang, X

2015-12-22

Antibody-mediated rejection (AMR) is an important factor affecting survival after renal transplantation. A highly selective proteasome inhibitor, bortezomib, clears activated plasma cells from the body and has important therapeutic effect on AMR. We investigated the effects of bortezomib on AMR in a patient after a second renal transplant. Biopsy confirmed the diagnosis of mixed cellular rejection and AMR. Bortezomib was administered on day 1 (1.3 mg/m(2)), day 4 (1.0 mg/m(2)), and day 8 (1.0 mg/m(2)). On the same days, 250 mg methylprednisolone was administered once, and cyclosporine dose (5 mg·kg(-1)·day(-1)) was reduced by 50%. Oral mycophenolate mofetil and steroid were withdrawn on day 1 of bortezomib treatment. Intermittent double-filtration plasmapheresis was also performed. We monitored parameters, including T lymphocyte subsets, CD139 and CD19 expression, panel reactive antibody (PRA), and serum creatinine concentration. At follow-up 6 months after bortezomib treatment, we observed: 1) serum creatinine stabilized at 130 μM from a peak level of 337 μM; 2) PRA decreased from a maximum of 66.7 to 0%; 3) blood plasma cell percentage rebounded after significantly decreasing following the first dose of bortezomib; 4) in renal allograft biopsy, immunohistochemical staining for C4d shifted from strongly positive to negative, and cellular rejection shifted from type IIA to borderline; and 5) adverse effects such as platelet suppression, hypotension, and grade 3 peripheral neuropathy emerged. Bortezomib effectively treated antibody-mediated renal transplantation rejection in this case study, but clinical trials with large sample sizes are still needed to explore clinical safety and tolerability.

Bortezomib induces apoptosis and suppresses cell growth and metastasis by inactivation of Stat3 signaling in chondrosarcoma.

Science.gov (United States)

Bao, Xing; Ren, Tingting; Huang, Yi; Ren, Chongmin; Yang, Kang; Zhang, Hongliang; Guo, Wei

2017-02-01

Bortezomib, formerly known as PS341, is a novel proteasome inhibitor with in vitro and in vivo antineoplastic effects in many malignancies. However, diverse antitumor mechanisms of bortezomib have been identified in many investigations and preclinical studies. Understanding the molecular and cellular mechanisms through which bortezomib acts will improve the therapeutic utility of this drug in different cancer types. In the present study, we investigated the in vitro and in vivo effects of bortezomib on chondrosarcoma. Bortezomib selectively inhibited cell growth in chondrosarcoma cells but not in normal articular cartilage cells. In addition to growth inhibition, apoptosis and cell cycle arrest, bortezomib triggered alleviation of migratory and invasive properties of chondrosarcoma cells. Mechanistically, signal transducer and activator of transcription 3 (Stat3) and its downstream targets Bcl-2, cyclin D1 and c-Myc was inactivated by bortezomib treatment. Accordingly, small interfering RNA (siRNA)-mediated Stat3 knockdown enhanced bortezomib-induced apoptosis, and concomitantly enhanced the inhibitory effect of bortezomib on cell viability, migration and invasion. Moreover, while Slug, MMP9, MMP2, CD44, N-cadherin and vimentin, the mesenchymal cell markers, were repressed by bortezomib concomitant increased expression of E-cadherin was observed. In vivo, bortezomib downregulated Stat3 activity and mesenchymal cell marker expression, induced apoptosis and inhibition of metastasis and tumor growth. Together, inactivation of Stat3 signaling contributes to bortezomib-induced inhibition of tumor growth, migration and invation on chondrosarcoma. Bortezomib demonstrates an antineoplastic role on chondrosarcoma both in vitro and in vivo. These beneficial effects can be explained by bortezomib-mediated Stat3 supression. The present study suggests a promising therapeutics target in chondrosarcoma and probably in other kinds of metastatic malignant tumors.

Ventricular fibrillation after bortezomib therapy in a patient with systemic amyloidosis

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Satoshi Yamasaki

2013-09-01

Full Text Available A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis.

Bortezomib-Induced Bronchiolitis Obliterans Organizing Pneumonia

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E. Vandeix

2012-01-01

Full Text Available Introduction. Bortezomib is a proteasome inhibitor indicated for the treatment of multiple myeloma patients. The most frequent side effects are gastrointestinal and neurological. Serious pulmonary complications have been described rarely. Observation. This case involves a 74-year-old man suffering from IgG Kappa myeloma treated with bortezomib, melphalan, and dexamethasone. After administering chemotherapy, the patient developed an acute respiratory distress syndrome (ARDS. A surgical pulmonary biopsy proved the existence of bronchiolitis obliterans organizing pneumonia (BOOP lesions. Systemic corticotherapy led to a rapid improvement in the patient’s condition. Conclusion. This is the first reported histologically confirmed case of bortezomid-induced BOOP. Faced with severe respiratory symptoms in the absence of other etiologies, complications due to bortezomid treatment should be evoked and corticotherapy considered.

An Improved Cambridge Filter Pad Extraction Methodology to Obtain More Accurate Water and “Tar” Values: In Situ Cambridge Filter Pad Extraction Methodology

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Ghosh David

2014-07-01

Full Text Available Previous investigations by others and internal investigations at Philip Morris International (PMI have shown that the standard trapping and extraction procedure used for conventional cigarettes, defined in the International Standard ISO 4387 (Cigarettes -- Determination of total and nicotine-free dry particulate matter using a routine analytical smoking machine, is not suitable for high-water content aerosols. Errors occur because of water losses during the opening of the Cambridge filter pad holder to remove the filter pad as well as during the manual handling of the filter pad, and because the commercially available filter pad holder, which is constructed out of plastic, may adsorb water. This results in inaccurate values for the water content, and erroneous and overestimated values for Nicotine Free Dry Particulate Matter (NFDPM. A modified 44 mm Cambridge filter pad holder and extraction equipment which supports in situ extraction methodology has been developed and tested. The principle of the in situ extraction methodology is to avoid any of the above mentioned water losses by extracting the loaded filter pad while kept in the Cambridge filter pad holder which is hermetically sealed by two caps. This is achieved by flushing the extraction solvent numerous times through the hermetically sealed Cambridge filter pad holder by means of an in situ extractor. The in situ methodology showed a significantly more complete water recovery, resulting in more accurate NFDPM values for high-water content aerosols compared to the standard ISO methodology. The work presented in this publication demonstrates that the in situ extraction methodology applies to a wider range of smoking products and smoking regimens, whereas the standard ISO methodology only applies to a limited range of smoking products and smoking regimens, e.g., conventional cigarettes smoked under ISO smoking regimen. In cases where a comparison of yields between the PMI HTP and

Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

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Kahl Brad S

2008-05-01

Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.

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Körner, Zandra; Fontes-Oliveira, Cibely C; Holmberg, Johan; Carmignac, Virginie; Durbeej, Madeleine

2014-05-01

Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model

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Wang Cun

2012-05-01

Full Text Available Abstract Background Despite recent advances in the treatment of hepatocellular carcinoma (HCC, the chemotherapy efficacy against HCC is still unsatisfactory. The mammalian target of rapamycin (mTOR has been emerged as an important cancer therapeutic target. However, HCC cells often resistant to rapamycin because of the paradoxical activation of Akt by rapamycin. In this study, we investigated whether bortezomib could enhance the antitumor effects of rapamycin. Methods The effects of rapamycin and bortezomib on HCC proliferation, apoptosis, migration, and invasiveness in vitro were assessed by CCK-8 analysis, flow cytometry, Hoechst 33342 staining and transwell assays, respectively. Total and phosphorylated protein levels of Akt were detected by Western blotting. The effects of rapamycin and/or bortezomib on the mRNA expression levels of p53, p27, p21 and Bcl-2 family in HCCLM3 cells were evaluated by RT-PCR. The roles of rapamycin and bortezomib on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. The effects of rapamycin and bortezomib on cell proliferation and apoptosis in vivo were test by PCNA and TUNEL staining. Results Bortezomib synergized with rapamycin to reduce cell growth, induce apoptosis, and inhibit cell mobility in vitro. Further mechanistic studies showed that bortezomib inhibited rapamycin-induced phosphorylated Akt, which in turn enhanced apoptosis of HCC cell lines. The alteration of the mRNA expression of cell cycle inhibitors p53, p27, p21 and apoptosis associated genes Bcl-2, Bax were also involved in the synergistic antitumor effects of rapamycin and bortezomib. P53 inhibitor PFT-α significantly attenuate the effect of rapamycin and bortezomib on cell apoptosis, which indicated that the pro-apoptotic effect of rapamycin and bortezomib may be p53-dependent. Treatment of HCCLM3-R bearing nude mice with rapamycin and bortezomib significantly enhanced tumor growth

A phase I trial of bortezomib and interferon-α-2b in metastatic melanoma.

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Markowitz, Joseph; Luedke, Eric A; Grignol, Valerie P; Hade, Erinn M; Paul, Bonnie K; Mundy-Bosse, Bethany L; Brooks, Taylor R; Dao, Thao-Vi; Kondalasula, Sri V; Lesinski, Gregory B; Olencki, Thomas; Kendra, Kari L; Carson, William E

2014-01-01

The possibility that cytokine administration could enhance the antitumor effects of proteasome inhibition was explored. It was found that coadministration of bortezomib and interferon-α (IFN-α) induced synergistic apoptosis in human melanoma cell lines and prolonged survival in a murine model of melanoma. A phase I study was conducted to determine the tolerability and the maximum tolerated dose of bortezomib when administered in combination with IFN-α-2b to patients with metastatic melanoma. Patients were treated on a 5-week cycle. In week 1 of cycle 1, patients received 5 million U/m(2) IFN-α subcutaneously thrice weekly. During weeks 2-4 of cycle 1, bortezomib was administered intravenously weekly along with IFN-α thrice weekly. There was a treatment break during week 5. After cycle 1, bortezomib was administered in combination with IFN-α. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m) to cohorts of 3 patients. Sixteen patients were treated (8 women, 8 men; median age 59 y). Common grade 3 toxicities included fatigue (5), vomiting (3), and diarrhea (3). Grade 4 toxicities included fatigue (3) and lymphopenia (1). The maximum tolerated dose for bortezomib was 1.3 mg/m(2). One patient had a partial response, and 7 had stable disease. Progression-free survival was 2.5 months, and overall survival was 10.3 months. Bortezomib administration did not augment the ability of IFN-α to induce phosphorylation of STAT1 in circulating immune cells; however, it did lead to reduced plasma levels of proangiogenic cytokines. The combination of bortezomib and IFN-α can be safely administered to melanoma patients.

Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline

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Reece, D.; Imrie, K.; Stevens, A.; Smith, C.A.

2006-01-01

Questions In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate? What is the toxicity associated with the use of bortezomib? Which patients are more or less likely to benefit from treatment with bortezomib? Perspectives Evidence was selected and reviewed by two members of the Hemato...

Inhibition of nuclear factor-κB and target genes during combined therapy with proteasome inhibitor bortezomib and reirradiation in patients with recurrent head-and-neck squamous cell carcinoma

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Van Waes, Carter; Chang, Angela A.; Lebowitz, Peter F.; Druzgal, Colleen H.; Chen, Zhong; Elsayed, Yusri A.; Sunwoo, John B.; Rudy, Susan; Morris, John C.; Mitchell, James B.; Camphausen, Kevin; Gius, David; Adams, Julian; Sausville, Edward A.; Conley, Barbara A.

2005-01-01

Purpose: To examine the effects the proteasome inhibitor bortezomib (VELCADE) on transcription factor nuclear factor-κB (NF-κB) and target genes and the feasibility of combination therapy with reirradiation in patients with recurrent head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: The tolerability and response to bortezomib 0.6 mg/m 2 and 0.9 mg/m 2 given twice weekly concurrent with daily reirradiation to 50-70 Gy was explored. Blood proteasome inhibition and NF-κB-modulated cytokines and factors were measured. Proteasome inhibition, nuclear localization of NF-κB phospho-p65, apoptosis, and expression of NF-κB-modulated mRNAs were compared in serial biopsies from accessible tumors. Results: The maximally tolerated dose was exceeded, and study was limited to 7 and 2 patients, respectively, given bortezomib 0.6 mg/m 2 and 0.9 mg/m 2 /dose with reirradiation. Grade 3 hypotension and hyponatremia were dose limiting. Mucositis was Grade 3 or less and was delayed. The mean blood proteasome inhibition at 1, 24, and 48 h after 0.6 mg/m 2 was 32%, 16%, and 7% and after 0.9 mg/m 2 was 56%, 26%, and 14%, respectively. Differences in proteasome and NF-κB activity, apoptosis, and expression of NF-κB-modulated cell cycle, apoptosis, and angiogenesis factor mRNAs were detected in 2 patients with minor tumor reductions and in serum NF-κB-modulated cytokines in 1 patient with a major tumor reduction. Conclusions: In combination with reirradiation, the maximally tolerated dose of bortezomib was exceeded at a dose of 0.6 mg/m 2 and the threshold of proteasome inhibition. Although this regimen with reirradiation is not feasible, bortezomib induced detectable differences in NF-κB localization, apoptosis, and NF-κB-modulated genes and cytokines in tumor and serum in association with tumor reduction, indicating that other schedules of bortezomib combined with primary radiotherapy or reirradiation may merit future investigation

Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.

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Valentina A Carozzi

Full Text Available Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations

A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma.

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Ogawa, Yoshiaki; Ogura, Michinori; Tobinai, Kensei; Ando, Kiyoshi; Suzuki, Tatsuya; Watanabe, Takashi; Ohmachi, Ken; Uchida, Toshiki; Hanson, Mary E; Tanaka, Yoshinobu; Koh, Yasuhiro; Shimamoto, Takashi; Hotta, Tomomitsu

2016-01-01

This study was undertaken to evaluate safety and pharmacokinetics and to determine treatment doses of vorinostat plus bortezomib in Japanese patients with relapsed or refractory multiple myeloma (MM). Of 9 originally enrolled patients, 2 were refractory to bortezomib, and both experienced dose-limiting toxicity (DLT), prompting a protocol amendment to exclude bortezomib-refractory individuals. Patients not considered bortezomib refractory (N = 7) received 21-day cycles of 1.3 mg/m(2) intravenous bortezomib (Days 1, 4, 8, and 11) and oral vorinostat 400 mg (Days 1 through 14) and were further evaluated. Vorinostat and bortezomib treatment doses were determined by DLT and safety, tolerability, and treatment response were assessed. Of 7 enrolled patients, 6 were evaluated, and one developed DLTs. The most common adverse events were leukopenia, neutropenia, thrombocytopenia, diarrhea, nausea, decreased appetite, and vomiting. Combination of vorinostat plus bortezomib did not increase vorinostat exposure at Day 11 [AUC0-24 h ratio (95% CI) = 1.08 (0.80, 1.45)]; geometric mean AUC0-24 h ratio for bortezomib (90% CI) was 1.96 (1.24-3.12). Objective therapeutic response occurred in 3 patients, including 1 complete response and 2 partial responses. Vorinostat 400 mg plus bortezomib 1.3 mg/m(2) was safe and well-tolerated in Japanese patients with relapsed or refractory MM not considered bortezomib refractory (NCT00858234).

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

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Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

2016-07-02

Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.

The protective effects of the proteasome inhibitor bortezomib (velcade on ischemia-reperfusion injury in the rat retina.

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Fang-Ting Chen

Full Text Available PURPOSE: To evaluate the protective effects of bortezomib (Velcade on ischemia-reperfusion (IR injury in the rat retina. METHODS: The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg, or high-dose bortezomib (0.2 mg/kg before the induction of IR injury. Electroretinography (ERG was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α, anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin, and pro-apoptotic proteins (p53, bax were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein, NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells. RESULTS: ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group. CONCLUSIONS: Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies.

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Schelman, William R; Traynor, Anne M; Holen, Kyle D; Kolesar, Jill M; Attia, Steven; Hoang, Tien; Eickhoff, Jens; Jiang, Zhisheng; Alberti, Dona; Marnocha, Rebecca; Reid, Joel M; Ames, Matthew M; McGovern, Renee M; Espinoza-Delgado, Igor; Wright, John J; Wilding, George; Bailey, Howard H

2013-12-01

A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors. Patients received vorinostat orally once daily on days 1-14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m(2)). Bortezomib dosing was increased using a standard phase I dose-escalation schema. PKs were evaluated during cycle 1. Twenty-three patients received 57 cycles of treatment on four dose levels ranging from bortezomib 0.7 mg/m(2) to 1.5 mg/m(2). The MTD was established at vorinostat 400 mg daily and bortezomib 1.3 mg/m(2). DLTs consisted of grade 3 fatigue in three patients (1 mg/m(2),1.3 mg/m(2) and 1.5 mg/m(2)) and grade 3 hyponatremia in one patient (1.5 mg/m(2)). The most common grade 1/2 toxicities included nausea (60.9%), fatigue (34.8%), diaphoresis (34.8%), anorexia (30.4%) and constipation (26.1%). Objective partial responses were observed in one patient with NSCLC and in one patient with treatment-refractory soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however, the Cmax and AUC of the acid metabolite were significantly increased on day 2 compared with day 1. This combination was generally well-tolerated at doses that achieved clinical benefit. The MTD was established at vorinostat 400 mg daily × 14 days and bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21-day cycle.

A phase II study of V-BEAM as conditioning regimen before second auto-SCT for multiple myeloma.

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Wang, T-F; Fiala, M A; Cashen, A F; Uy, G L; Abboud, C N; Fletcher, T; Wu, N; Westervelt, P; DiPersio, J F; Stockerl-Goldstein, K E; Vij, R

2014-11-01

High-dose melphalan has been the standard conditioning regimen for auto-SCT in multiple myeloma (MM) for decades. A more effective conditioning regimen may induce deeper responses and longer remission duration. It is especially needed in the setting of second auto-SCT, which rarely achieves comparable results with the first auto-SCT using the same conditioning regimen. Here we conducted a phase II study to investigate the efficacy and safety of a conditioning regimen V-BEAM (bortezomib-BEAM) before second auto-SCT for multiple myeloma. Ten patients were enrolled from September 2012 to May 2013. The CR rate at day +100 after auto-SCT was 75%; all except for one patient remained in remission after a median follow-up of 6 months. Three patients developed Clostridium difficile infection. Two patients died within the first 30 days of auto-SCT from neutropenic colitis and overwhelming sepsis, respectively. Due to the high rate of morbidity and mortality, the study was terminated after 10 patients. In summary, although the conditioning regimen V-BEAM before second auto-SCT for MM provided promising responses, it was associated with unexpected treatment-related toxicity and should not be investigated further without modifications.

Bortezomib induces neuropathic pain through protein kinase C-mediated activation of presynaptic NMDA receptors in the spinal cord.

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Xie, Jing-Dun; Chen, Shao-Rui; Chen, Hong; Pan, Hui-Lin

2017-09-01

Chemotherapeutic drugs, including bortezomib, often cause painful peripheral neuropathy, which is a severe dose-limiting adverse effect experienced by many cancer patients. The glutamate N-methyl-d-aspartate receptors (NMDARs) at the spinal cord level are critically involved in the synaptic plasticity associated with neuropathic pain. In this study, we determined whether treatment with bortezomib, a proteasome inhibitor, affects the NMDAR activity of spinal dorsal horn neurons. Systemic treatment with bortezomib in rats did not significantly affect postsynaptic NMDAR currents elicited by puff application of NMDA directly to dorsal horn neurons. Bortezomib treatment markedly increased the baseline frequency of miniature excitatory postsynaptic currents (EPSCs), which was completely normalized by the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5). AP5 also reduced the amplitude of monosynaptic EPSCs evoked by dorsal root stimulation in bortezomib-treated, but not vehicle-treated, rats. Furthermore, inhibition of protein kinase C (PKC) with chelerythrine fully reversed the increased frequency of miniature EPSCs and the amplitude of evoked EPSCs in bortezomib-treated rats. Intrathecal injection of AP5 and chelerythrine both profoundly attenuated mechanical allodynia and hyperalgesia induced by systemic treatment with bortezomib. In addition, treatment with bortezomib induced striking membrane translocation of PKC-βII, PKC-δ, and PKC-ε in the dorsal root ganglion. Our findings indicate that bortezomib treatment potentiates nociceptive input from primary afferent nerves via PKC-mediated tonic activation of presynaptic NMDARs. Targeting presynaptic NMDARs and PKC at the spinal cord level may be an effective strategy for treating chemotherapy-induced neuropathic pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bortezomib-induced acute pancreatitis: Case report and review of the literature.

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Talamo, Giampaolo; Sivik, Jeffrey; Pandey, Manoj K; Mir, Muhammad A

2016-04-01

Acute pancreatitis is a rare complication of chemotherapy agents. We describe the case of a patient with multiple myeloma who developed acute pancreatitis after treatment with bortezomib, a proteasome inhibitor commonly used in the treatment of this disease. We reviewed the available medical literature on this topic, and found other seven similar cases, all after intravenous bortezomib. Our case is the first one occurring with the subcutaneous route of administration. © The Author(s) 2014.

Preferential cytotoxicity of bortezomib toward highly malignant human liposarcoma cells via suppression of MDR1 expression and function

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Hu, Yamei; Wang, Lingxian; Wang, Lu; Wu, Xuefeng; Wu, Xudong; Gu, Yanhong; Shu, Yongqian; Sun, Yang; Shen, Yan; Xu, Qiang

2015-01-01

Liposarcoma is the most common soft tissue sarcoma with a high risk of relapse. Few therapeutic options are available for the aggressive local or metastatic disease. Here, we report that the clinically used proteasome inhibitor bortezomib exhibits significantly stronger cytotoxicity toward highly malignant human liposarcoma SW872-S cells compared with its parental SW872 cells, which is accompanied by enhanced activation of apoptotic signaling both in vitro and in vivo. Treatment of cells with Jun-N-terminal kinase (JNK) inhibitor SP60015 or the translation inhibitor cycloheximide ameliorated this enhanced apoptosis. Bortezomib inhibited MDR1 expression and function more effectively in SW872-S cells than in SW872 cells, indicating that the increased cytotoxicity relies on the degree of proteasome inhibition. Furthermore, the pharmacological or genetic inhibition of sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2, which is highly expressed in SW872-S cells, resulted in partial reversal of cell growth inhibition and increase of MDR1 expression in bortezomib-treated SW872-S cells. These results show that bortezomib exhibits preferential cytotoxicity toward SW872-S cells possibly via highly expressed SERCA2-associated MDR1 suppression and suggest that bortezomib may serve as a potent agent for treating advanced liposarcoma. - Highlights: • We compare the cytotoxicity of different drugs between SW872-S and SW872 cells. • Highly malignant liposarcoma cells SW872-S show hypersensitivity to bortezomib. • Apoptotic signaling is robustly enhanced in bortezomib-treated SW872-S cells. • Bortezomib has strong suppression on MDR1 expression and function in SW872-S cells. • Inhibition of SERCA2 protects SW872-S cells from bortezomib

Preferential cytotoxicity of bortezomib toward highly malignant human liposarcoma cells via suppression of MDR1 expression and function

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Hu, Yamei; Wang, Lingxian; Wang, Lu; Wu, Xuefeng; Wu, Xudong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yanhong; Shu, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Sun, Yang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Shen, Yan, E-mail: shenyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

2015-02-15

Liposarcoma is the most common soft tissue sarcoma with a high risk of relapse. Few therapeutic options are available for the aggressive local or metastatic disease. Here, we report that the clinically used proteasome inhibitor bortezomib exhibits significantly stronger cytotoxicity toward highly malignant human liposarcoma SW872-S cells compared with its parental SW872 cells, which is accompanied by enhanced activation of apoptotic signaling both in vitro and in vivo. Treatment of cells with Jun-N-terminal kinase (JNK) inhibitor SP60015 or the translation inhibitor cycloheximide ameliorated this enhanced apoptosis. Bortezomib inhibited MDR1 expression and function more effectively in SW872-S cells than in SW872 cells, indicating that the increased cytotoxicity relies on the degree of proteasome inhibition. Furthermore, the pharmacological or genetic inhibition of sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2, which is highly expressed in SW872-S cells, resulted in partial reversal of cell growth inhibition and increase of MDR1 expression in bortezomib-treated SW872-S cells. These results show that bortezomib exhibits preferential cytotoxicity toward SW872-S cells possibly via highly expressed SERCA2-associated MDR1 suppression and suggest that bortezomib may serve as a potent agent for treating advanced liposarcoma. - Highlights: • We compare the cytotoxicity of different drugs between SW872-S and SW872 cells. • Highly malignant liposarcoma cells SW872-S show hypersensitivity to bortezomib. • Apoptotic signaling is robustly enhanced in bortezomib-treated SW872-S cells. • Bortezomib has strong suppression on MDR1 expression and function in SW872-S cells. • Inhibition of SERCA2 protects SW872-S cells from bortezomib.

Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.

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Peng, Ling; Ye, Xianghua; Zhou, Yun; Zhang, Junyan; Zhao, Qiong

2015-09-01

Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo. We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies. Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib. Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.

An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma

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Kim, George P.; Mahoney, Michelle R.; Szydlo, Daniel; Mok, Tony S. K.; Marshke, Robert; Holen, Kyle; Picus, Joel; Boyer, Michael; Pitot, Henry C.; Rubin, Joseph; Philip, Philip A.; Nowak, Anna; Wright, John J.; Erlichman, Charles

2013-01-01

Summary Background and Rationale Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitinproteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Results Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1–12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. Conclusions This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib. PMID:20839030

Inhibition of inducible heat shock protein-70 (hsp72 enhances bortezomib-induced cell death in human bladder cancer cells.

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Wei Qi

Full Text Available The proteasome inhibitor bortezomib (Velcade is a promising new agent for bladder cancer therapy, but inducible cytoprotective mechanisms may limit its potential efficacy. We used whole genome mRNA expression profiling to study the effects of bortezomib on stress-induced gene expression in a panel of human bladder cancer cell lines. Bortezomib induced strong upregulation of the inducible HSP70 isoforms HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A(high cells, but only induced the HSPA1B isoform in UM-UC10 and UM-UC13 (HSPA1A(low cells. Bortezomib stimulated the binding of heat shock factor-1 (HSF1 to the HSPA1A promoter in 253JB-V but not in UM-UC13 cells. Methylation-specific PCR revealed that the HSPA1A promoter was methylated in the HSPA1A(low cell lines (UM-UC10 and UM-UC13, and exposure to the chromatin demethylating agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72 promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas transient knockdown of HSPA1B further sensitized these cells to bortezomib, and exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J B-V promoted sensitivity to bortezomib in vitro and in tumor xenografts in vivo. Together, our results provide proof-of-concept for using Hsp72 inhibitors to promote bortezomib sensitivity in bladder cancers and suggest that selective targeting of HSPA1B could produce synthetic lethality in tumors that display HSPA1A promoter methylation.

Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies

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Kubicek, Gregory J. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Axelrod, Rita S. [Department of Medical Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Machtay, Mitchell [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States); Ahn, Peter H.; Anne, Pramila R. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Fogh, Shannon [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Cognetti, David [Department of Otolaryngology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Myers, Thomas J. [EMD Serono, Rockland, MA (United States); Curran, Walter J. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P., E-mail: Adam.dicker@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States)

2012-07-15

Purpose: Advanced head-and-neck cancer (HNC) remains a difficult disease to cure. Proteasome inhibitors such as bortezomib have the potential to improve survival over chemoradiotherapy alone. This Phase I dose-escalation study examined the potential of bortezomib in combination with cisplatin chemotherapy and concurrent radiation in the treatment of locally advanced and recurrent HNC. Methods and Materials: Eligible patients received cisplatin once weekly at 30 mg/m{sup 2} per week and bortezomib along with concurrent radiation. Bortezomib was given on Days 1, 4, 8, and 11 every 3 weeks, with an initial starting dose of 0.7 mg/m{sup 2} and escalation levels of 1.0 and 1.3 mg/m{sup 2}. Dose escalation was performed only after assessment to rule out any dose-limiting toxicity. Results: We enrolled 27 patients with HNC, including 17 patients with recurrent disease who had received prior irradiation. Patients received bortezomib dose levels of 0.7 mg/m{sup 2} (7 patients), 1.0 mg/m{sup 2} (10 patients), and 1.3 mg/m{sup 2} (10 patients). No Grade 5 toxicities, 3 Grade 4 toxicities (all hematologic and considered dose-limiting toxicities), and 39 Grade 3 toxicities (in 20 patients) were observed. With a median follow-up of 7.4 months, the overall median survival was 24.7 months (48.4 months for advanced HNC patients and 15.4 months for recurrent HNC patients). Conclusion: Bortezomib in combination with radiation therapy and cisplatin chemotherapy is safe in the treatment of HNC with a bortezomib maximum tolerated dose of 1.0 mg/m{sup 2} in patients previously treated for HNC and 1.3 mg/m{sup 2} in radiation-naive patients.

Synergistic Effect and Molecular Mechanism of Homoharringtonine and Bortezomib on SKM-1 Cell Apoptosis.

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Jing Zhang

Full Text Available Myelodysplastic syndromes (MDS are clonal marrow stem-cell disorders with a high risk of progression to acute myeloid leukemia (AML. Treatment options are limited and targeted therapies are not available for MDS. In the present study, we investigated the cytotoxicity and the molecular mechanism of Homoharringtonine (HHT and Bortezomib towards high-risk MDS cell line SKM-1 in vitro and the role of miR-3151 was first evaluated in SKM-1 cells.SKM-1 cells were treated with different concentrations of HHT or Bortezomib, and cell viability was analyzed with CCK-8 assay. The influence on cell proliferation, cell cycle distribution and the percentage of apoptosis cells were analyzed by flow cytometry. Calcusyn software was used to calculate combination index (CI values. Western blot was used to analysis phosphorylation of Akt and nuclear NF-κB protein expression in SKM-1 cells. Mature miR-3151 level and p53 protein level were detected after HHT or Bortezomib treatment. The cell proliferation and p53 protein level were reassessed in SKM-1 cells infected with lentivirus to overexpress miR-3151.Simultaneous exposure to HHT and Bortezomib (10.4:1 resulted in a significant reduction of cell proliferation in SKM-1 cells (P < 0.05. Cell cycle arrest at G0/G1 and G2/M phase was observed (P < 0.05. HHT and Bortezomib synergistically induced cell apoptosis by regulating members of caspase 9, caspase 3 and Bcl-2 family (P < 0.01. The mechanisms of the synergy involved Akt and NF-κB signaling pathway inhibition, downregulation of mature miR-3151 and increment of downstream p53 protein level. Overexpression of miR-3151 promoted cell proliferation and inhibited p53 protein expression in SKM-1 (P < 0.01.HHT and Bortezomib synergistically inhibit SKM-1 cell proliferation and induce apoptosis in vitro. Inhibition of Akt and NF-κB pathway signaling contribute to molecular mechanism of HHT and Bortezomib. miR-3151 abundance is implicated in SKM-1 cell viability, cell

Herpes zoster in multiple myeloma patients during bortezomib treatment

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I. N. Nazarova

2011-01-01

Full Text Available Recent advances in multiple myeloma (MM treatment associated with new drug use including bortezomib. Experiences in wide ambul atory drug use confirm therapy success for this serious disease, but at the same time reveals the most common side effects. One of th e most significant is the reactivation of Herpes zoster , which leads to decrease MM therapy results because of inability to perform standard therapy in these patients. Literature data and own experiences about reactivation of Herpes zoster during bortezomib therapy as monothe rapy and in combination, which varies from 7 to 34% according to different authors and 25% of own experiences, is presented. Treatment and preventive schedule of this complication are shown.

Use of bortezomib in heavy-chain deposition disease: a report of 3 cases.

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Patel, Kinjal; Dillon, John J; Leung, Nelson; Bomback, Andrew S; Appel, Gerald B; D'Agati, Vivette; Canetta, Pietro A

2014-07-01

Heavy-chain deposition disease (HCDD) is a rare complication of plasma cell dyscrasia in which monoclonal heavy chains deposit in glomerular and tubular basement membranes of the kidney. Clinical and pathologic features of HCDD have been well described in case reports and series, but evidence supporting specific therapies is sparse. Historically, the disease has had a poor prognosis, intensifying the need to clarify optimal treatments. We describe 3 cases of HCDD with biopsy-proven glomerular involvement, severe nephrotic syndrome, and decline in kidney function that were treated successfully with bortezomib, a proteasome inhibitor. None of these patients had multiple myeloma. In all cases, bortezomib-based therapy resulted in sustained resolution of nephrotic syndrome and improvement in kidney function. All 3 patients developed peripheral neuropathy; otherwise, treatment was well tolerated. To our knowledge, this is the first description of the clinical effectiveness of bortezomib against HCDD. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Dorsal Column Degeneration after Bortezomib Therapy in a Patient with Multiple Myeloma

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Tatsuro Joh

2009-10-01

Full Text Available We present here a case of dorsal column degeneration in a female patient with multiple myeloma following exposure to bortezomib. Two days after intravenous administration of a first course of bortezomib 1 mg/m2, the patient developed rapidly-progressive numbness, pain and muscle weakness in the bilateral upper and lower limbs. Following gancyclovir treatment of subsequent cytomegalovirus viremia, the patient went on to receive a course of EPOCH (etoposide 50 mg/m2/day on days 1–4, vincristine 0.4 mg/m2/day on days 1–4, doxorubicin 10 mg/m2/day on days 1–4, cyclophosphamide 750 mg/m2/day on day 6, and prednisolone 60 mg/m2/day on days 1–6. Shortly thereafter, the patient developed bilateral Aspergillus pneumonia. Despite treatment with appropriate antifungal agents, the patient died from respiratory failure due to bilateral diffuse alveolar damage of the lungs and without recovery of severe sensory and motor neuropathy prior to her death. Post mortem examination revealed spongy degeneration of the dorsal column from the medulla oblongata to the cervical spinal cord. Bortezomib-associated peripheral neuropathy in patients with multiple myeloma has been commonly reported but appears to resolve in a majority of these patients after dose reduction or discontinuation. We believe this to be the first report of spinal cord abnormalities in a patient with multiple myeloma treated with bortezomib. Further investigation is required to ascertain the exact mechanism of this central neurotoxic effect and to identify appropriate neuroprotective strategies.

Curcumin Enhances Bortezomib Treatment of Myeloma by Inhibiting ...

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Purpose: To investigate whether curcumin augments bortezomib-induced apoptosis in myeloma cells (MM1.R line), and to explore the molecular mechanism with regard to heat shock protein 90 (HSP90) expression. Methods: MTT cell viability assay was used to assess growth inhibition of MM1.R cells at different ...

Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease

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Sezer, Orhan; Beksac, Meral; Hajek, Roman

2017-01-01

This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles...... from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P...... with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival....

Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma

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San-Miguel, Jesús F; Hungria, Vânia T M; Yoon, Sung-Soo

2014-01-01

with bortezomib (1·3 mg/m(2) on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression...

Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study.

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Rosiñol, Laura; Oriol, Albert; Teruel, Ana Isabel; Hernández, Dolores; López-Jiménez, Javier; de la Rubia, Javier; Granell, Miquel; Besalduch, Joan; Palomera, Luis; González, Yolanda; Etxebeste, María Asunción; Díaz-Mediavilla, Joaquín; Hernández, Miguel T; de Arriba, Felipe; Gutiérrez, Norma C; Martín-Ramos, María Luisa; Cibeira, María Teresa; Mateos, María Victoria; Martínez, Joaquín; Alegre, Adrián; Lahuerta, Juan José; San Miguel, Jesús; Bladé, Joan

2012-08-23

The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/VBAD/B (35% vs 21%, P = .01). The median progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P = .01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/VBAD/B (46% vs 38%, P = .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).

Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

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T.B.M. Castro

2016-01-01

Full Text Available In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61% vs 23 (39% males, and of whites, 49 (83.1% vs 10 (16.9% blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6. Regarding staging at diagnosis, 27 (45.7% patients were in stage III-A, with 12 (20.3% patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40 were: neutropenia (42.5%, diarrhea (47.5%, and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26 and sc (n=14 administration routes (P=0.343. In the group treated with thalidomide (n=19, 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038. Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%. Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

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Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-08-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

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Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

2013-05-01

Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

Neurotoxicity to DRG neurons varies between rodent strains treated with cisplatin and bortezomib.

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Podratz, Jewel L; Kulkarni, Amit; Pleticha, Josef; Kanwar, Rahul; Beutler, Andreas S; Staff, Nathan P; Windebank, Anthony J

2016-03-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect that can lead to long-term morbidity. Approximately one-third of patients receiving chemotherapy with taxanes, vinca alkaloids, platinum compounds or proteasome inhibitors develop this toxic side effect. It is not possible to predict who will get CIPN, however, genetic susceptibility may play a role. We explored this hypothesis using an established in vitro dorsal root ganglia neurite outgrowth (DRG-NOG) assay to assess possible genetic influences for cisplatin- and bortezomib-induced neurotoxicity. Almost all previous in vitro studies have used rats or mice. We compared DRG-NOG between four genetically defined, inbred mouse strains (C57BL/6J, DBA/2J, BALB/cJ, and C3H/HeJ) and one rat strain (Sprague Dawley). Our studies found differences in cisplatin and bortezomib-induced neurotoxicity between mouse and rat strains and between the different mouse strains. C57BL/6J and Balb/cJ DRG-NOG was more sensitive to cisplatin than DBA/2J and C3H/HeJ DRG-NOG, and all mouse strains were more sensitive to cisplatin than rat. Bortezomib induced a biphasic dose response in DBA/2J and C3H/H3J mice. C57BL/6J DRG-NOG was most sensitive and Balb/cJ DRG-NOG was least sensitive to bortezomib. Our animal data supports the hypothesis that genetic background may play a role in CIPN and care must be taken when rodent models are used to better understand the contribution of genetics in patient susceptibility to CIPN. Copyright © 2016 Elsevier B.V. All rights reserved.

Curcumin and Its Analogue Induce Apoptosis in Leukemia Cells and Have Additive Effects with Bortezomib in Cellular and Xenograft Models

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L. I. Nagy

2015-01-01

Full Text Available Combination therapy of bortezomib with other chemotherapeutics is an emerging treatment strategy. Since both curcumin and bortezomib inhibit NF-κB, we tested the effects of their combination on leukemia cells. To improve potency, a novel Mannich-type curcumin derivative, C-150, was synthesized. Curcumin and its analogue showed potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60, with different potency but similar additive properties with bortezomib. Additive antiproliferative effects were correlated well with LPS-induced NF-κB inhibition results. Gene expression data on cell cycle and apoptosis related genes, obtained by high-throughput QPCR, showed that curcumin and its analogue act through similar signaling pathways. In correlation with in vitro results similar additive effect could be obsereved in SCID mice inoculated systemically with HL60 cells. C-150 in a liposomal formulation given intravenously in combination with bortezomib was more efficient than either of the drugs alone. As our novel curcumin analogue exerted anticancer effects in leukemic cells at submicromolar concentration in vitro and at 3 mg/kg dose in vivo, which was potentiated by bortezomib, it holds a great promise as a future therapeutic agent in the treatment of leukemia alone or in combination.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

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Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

A network biology approach evaluating the anticancer effects of bortezomib identifies SPARC as a therapeutic target in adult T-cell leukemia cells

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Yu Zhang

2008-10-01

Full Text Available Junko H Ohyashiki1, Ryoko Hamamura2, Chiaki Kobayashi2, Yu Zhang2, Kazuma Ohyashiki21Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan; 2First Department of Internal Medicine, Tokyo Medical University, Tokyo, JapanAbstract: There is a need to identify the regulatory gene interaction of anticancer drugs on target cancer cells. Whole genome expression profiling offers promise in this regard, but can be complicated by the challenge of identifying the genes affected by hundreds to thousands of genes that induce changes in expression. A proteasome inhibitor, bortezomib, could be a potential therapeutic agent in treating adult T-cell leukemia (ATL patients, however, the underlying mechanism by which bortezomib induces cell death in ATL cells via gene regulatory network has not been fully elucidated. Here we show that a Bayesian statistical framework by VoyaGene® identified a secreted protein acidic and rich in cysteine (SPARC gene, a tumor-invasiveness related gene, as a possible modulator of bortezomib-induced cell death in ATL cells. Functional analysis using RNAi experiments revealed that inhibition of the expression SPARC by siRNA enhanced the apoptotic effect of bortezomib on ATL cells in accordance with an increase of cleaved caspase 3. Targeting SPARC may help to treat ATL patients in combination with bortezomib. This work shows that a network biology approach can be used advantageously to identify the genetic interaction related to anticancer effects.Keywords: network biology, adult T cell leukemia, bortezomib, SPARC

Induction regimens for transplant-eligible patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

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Zeng ZH

2017-07-01

Full Text Available Zi-Hang Zeng,1,2 Jia-Feng Chen,1,2 Yi-Xuan Li,1,2 Ran Zhang,1,2 Ling-Fei Xiao,1,2 Xiang-Yu Meng1,2 1Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, 2Department of Evidence-Based Medicine and Clinical Epidemiology, Second Clinical College of Wuhan University, Wuhan, People’s Republic of China Objective: The aim of this study was to compare the early efficacy and survivals of induction regimens for transplant-eligible patients with untreated multiple myeloma. Materials and methods: A comprehensive literature search in electronic databases was conducted for relevant randomized controlled trials (RCTs. Eligible studies were selected according to the predefined selection criteria, before they were evaluated for methodological quality. Basic characteristics and data for network meta-analysis (NMA were extracted from included trials and pooled in our meta-analysis. The end points were the overall response rate (ORR, progression-free survival (PFS, and overall survival (OS. Results: A total of 14 RCTs that included 4,763 patients were analyzed. The post-induction ORR was higher with bortezomib plus thalidomide plus dexamethasone (VTD regimens, and VTD was better than the majority of other regimens. For OS, VTD plus cyclophosphamide (VTDC regimens showed potential superiority over other regimens, but the difference was not statistically significant. The PFS was longer with thalidomide plus doxorubicin plus dexamethasone (TAD regimens for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM. Conclusion: The NMA demonstrated that the VTD, VTDC, and TAD regimens are most beneficial in terms of ORR, OS, and PFS for transplant-eligible patients with NDMM, respectively. Keywords: multiple myeloma, newly diagnosed, transplant-eligible, induction therapies, network meta-analysis

Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization.

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Niesvizky, Ruben; Mark, Tomer M; Ward, Maureen; Jayabalan, David S; Pearse, Roger N; Manco, Megan; Stern, Jessica; Christos, Paul J; Mathews, Lena; Shore, Tsiporah B; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E

2013-03-15

This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

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LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Acquired von Willebrand Syndrome Associated to Secondary IgM MGUS Emerging after Autologous Stem Cell Transplantation for AL Amyloidosis.

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Qamar, Hina; Lee, Adrienne; Valentine, Karen; Skeith, Leslie; Jimenez-Zepeda, Victor H

2017-01-01

Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT). Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

Directory of Open Access Journals (Sweden)

Victor H Jimenez-Zepeda

2017-05-01

Full Text Available Acquired von Willebrand syndrome (AVWS is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT. Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

Synergistic induction of apoptosis in multiple myeloma cells by bortezomib and hypoxia-activated prodrug TH-302, in vivo and in vitro.

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Hu, Jinsong; Van Valckenborgh, Els; Xu, Dehui; Menu, Eline; De Raeve, Hendrik; De Bruyne, Elke; De Bryune, Elke; Xu, Song; Van Camp, Ben; Handisides, Damian; Hart, Charles P; Vanderkerken, Karin

2013-09-01

Recently, we showed that hypoxia is a critical microenvironmental factor in multiple myeloma, and that the hypoxia-activated prodrug TH-302 selectively targets hypoxic multiple myeloma cells and improves multiple disease parameters in vivo. To explore approaches for sensitizing multiple myeloma cells to TH-302, we evaluated in this study the antitumor effect of TH-302 in combination with the clinically used proteasome inhibitor bortezomib. First, we show that TH-302 and bortezomib synergistically induce apoptosis in multiple myeloma cell lines in vitro. Second, we confirm that this synergism is related to the activation of caspase cascades and is mediated by changes of Bcl-2 family proteins. The combination treatment induces enhanced cleavage of caspase-3/8/9 and PARP, and therefore triggers apoptosis and enhances the cleavage of proapoptotic BH3-only protein BAD and BID as well as the antiapoptotic protein Mcl-1. In particular, TH-302 can abrogate the accumulation of antiapoptotic Mcl-1 induced by bortezomib, and decreases the expression of the prosurvival proteins Bcl-2 and Bcl-xL. Furthermore, we found that the induction of the proapoptotic BH3-only proteins PUMA (p53-upregulated modulator of apoptosis) and NOXA is associated with this synergism. In response to the genotoxic and endoplasmic reticulum stresses by TH-302 and bortezomib, the expression of PUMA and NOXA were upregulated in p53-dependent and -independent manners. Finally, in the murine 5T33MMvv model, we showed that the combination of TH-302 and bortezomib can improve multiple disease parameters and significantly prolong the survival of diseased mice. In conclusion, our studies provide a rationale for clinical evaluation of the combination of TH-302 and bortezomib in patients with multiple myeloma.

Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.

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Dimopoulos, Meletios A; Goldschmidt, Hartmut; Niesvizky, Ruben; Joshua, Douglas; Chng, Wee-Joo; Oriol, Albert; Orlowski, Robert Z; Ludwig, Heinz; Facon, Thierry; Hajek, Roman; Weisel, Katja; Hungria, Vania; Minuk, Leonard; Feng, Shibao; Zahlten-Kumeli, Anita; Kimball, Amy S; Moreau, Philippe

2017-10-01

The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups. ENDEAVOR was a phase 3, open-label, randomised controlled trial in patients with relapsed or refractory multiple myeloma. Patients were recruited from 198 hospitals and outpatient clinics in 27 countries in Europe, North America, South America, and the Asia-Pacific region. Patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and had received between one and three previous lines of therapy. Patients were randomly assigned (1:1) to receive carfilzomib and dexamethasone (carfilzomib group) or bortezomib and dexamethasone (bortezomib group) through a blocked randomisation scheme (block size of four), stratified by International Staging System stage, previous lines of treatment, previous proteasome inhibitor therapy, and planned route of bortezomib delivery if assigned to the bortezomib group. Carfilzomib (20 mg/m 2 on days 1 and 2 of cycle 1; 56 mg/m 2 thereafter) was given as a 30-min intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles; bortezomib (1·3 mg/m 2 ) was given as an intravenous bolus or subcutaneous injection on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20 mg oral or intravenous infusion) was given on days 1, 2, 8, 9, 15, 16, 22, and 23 in the carfilzomib group and on days 1, 2, 4, 5, 8, 9, 11, and 12 in the bortezomib group. The primary endpoint of ENDEAVOR, progression-free survival, has been previously reported. A stratified log-rank test was used to compare overall survival between treatment groups for this prospectively planned second interim

Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage.

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Premkumar, Daniel R; Jane, Esther P; Agostino, Naomi R; DiDomenico, Joseph D; Pollack, Ian F

2013-02-01

Glioblastomas are invasive tumors with poor prognosis despite current therapies. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth, and we and others have noted some antiglioma activity from HDACIs, such as vorinostat, although insufficient to warrant use as monotherapy. We have recently demonstrated that proteasome inhibitors, such as bortezomib, dramatically sensitized highly resistant glioma cells to apoptosis induction, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with vorinostat treatment alone, the combination of vorinostat plus bortezomib significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib with vorinostat enhanced apoptosis by increasing Mcl-1 cleavage, Noxa upregulation, Bak and Bax activation, and cytochrome c release. Further downregulation of Mcl-1 using shRNA enhanced cell killing by the bortezomib/vorinostat combination. Vorinostat induced a rapid and sustained phosphorylation of histone H2AX in primary GBM and T98G cells, and this effect was significantly enhanced by co-administration of bortezomib. Vorinostat/bortezomib combination also induced Rad51 downregulation, which plays an important role in the synergistic enhancement of DNA damage and apoptosis. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients. Copyright © 2011 Wiley Periodicals, Inc.

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

DEFF Research Database (Denmark)

Nijhof, I. S.; Groen, R. W. J.; Noort, W. A.

2015-01-01

lenalidomide- and/or bortezomib-refractory patients. In these assays, lenalidomide but not bortezomib, synergistically enhanced daratumumab-mediated multiple myeloma lysis through activation of natural killer cells. Finally, in an in vivo xenograft model, only the combination of daratumumab with lenalidomide......Purpose: Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, the prognosis of patients with multiple myeloma who become refractory to the novel agents lenalidomide and bortezomib is very poor, indicating the urgent need for new...... therapeutic options for these patients. The human CD38 monoclonal antibody daratumumab is being evaluated as a novel therapy for multiple myeloma. Prompted with the encouraging results of ongoing clinical phase I/II trials, we now addressed the potential value of daratumumab alone or in combination...

Bortezomib: a novel therapy approved for multiple myeloma.

Science.gov (United States)

Richardson, Paul G; Anderson, Kenneth C

2003-10-01

Cellular homeostasis requires routine degradation of key regulatory proteins, including tumor suppressor gene products, transcription factors, cell-cycle proteins and their inhibitors, as well as damaged and misfolded proteins. A critical part of this process is mediated by the 26S proteasome, a multi-subunit enzyme found in the nucleus and cytoplasm of all eukaryotic cells. Because of its essential role in many cellular processes controlling growth and survival, the proteasome has been identified as a potential target for cancer therapy. Drugs known to inhibit proteasome activity have been shown to induce cell-cycle arrest and programmed cell death (apoptosis). The impact of this finding is heightened by research showing that cancer cells are more sensitive to the proapoptotic effects of proteasome inhibition than normal cells. Preclinical evidence using bortezomib, the only proteasome inhibitor to enter clinical trials, suggests that proteasome inhibition may be effective in the treatment of hematologic and solid malignancies by promoting apoptosis, retarding angiogenesis, and inhibiting tumor cell adhesion and production of growth factors by acting on molecules such as nuclear factor-kappaB. Further preclinical evidence suggests that the antitumor effects of cytotoxic chemotherapy or radiotherapy may be enhanced by the addition of a proteasome inhibitor. Bortezomib was recently approved for the treatment of multiple myeloma. It is currently being investigated, both as a single agent and in combination, in phase I and II trials in a variety of tumor types.

A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.

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Shah, Manish A; Power, Derek G; Kindler, Hedy L; Holen, Kyle D; Kemeny, Margaret M; Ilson, David H; Tang, Laura; Capanu, Marinela; Wright, John J; Kelsen, David P

2011-12-01

The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in gastric adenocarcinoma. We performed a phase II trial of bortezomib in patients with advanced gastric adenocarcinoma. Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 every 21 days. The primary endpoint was objective response rate(RR); the null hypothesis was RR <1% versus the alternative ≥15%. One response in the first stage(15 patients) was required before proceeding with an additional 18 patients. If at least 2 or more responses out of 33 were observed, further study with bortezomib was warranted. Correlative studies evaluated pre-treatment tumor expression of NFkB, IkB, p53, p21, and cyclin D1. We enrolled 16 patients (15 evaluable for response) from four institutions. No patients demonstrated an objective response(95% CI, 0-22%); one patient achieved stable disease. Fourteen out of 16 patients experienced ≥ grade 2 toxicity. The most common toxicity was fatigue in six patients (n = 4 grade 2, n = 2 grade 3). Seven patients experienced neuropathy (n = 5 grade 1, and 1 each grade 2 and 3). Seven (60%) had high cytoplasmic staining for NFkB. Single agent bortezomib is inactive in metastatic gastric adenocarcinoma and should not be pursued. Future study of proteasome inhibition in gastric adenocarcinoma should be considered in combination with targeted inhibition of other non-overlapping oncogenic pathways as a potential rational approach.

Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.

Science.gov (United States)

Niesvizky, Ruben; Badros, Ashraf Z; Costa, Luciano J; Ely, Scott A; Singhal, Seema B; Stadtmauer, Edward A; Haideri, Nisreen A; Yacoub, Abdulraheem; Hess, Georg; Lentzsch, Suzanne; Spicka, Ivan; Chanan-Khan, Asher A; Raab, Marc S; Tarantolo, Stefano; Vij, Ravi; Zonder, Jeffrey A; Huang, Xiangao; Jayabalan, David; Di Liberto, Maurizio; Huang, Xin; Jiang, Yuqiu; Kim, Sindy T; Randolph, Sophia; Chen-Kiang, Selina

2015-01-01

This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m2 (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were grade≤3. At a bortezomib dose lower than that in other combination therapy studies, antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 5 (20%) patients; 11 (44%) achieved stable disease. Biomarker and pharmacodynamic assessments demonstrated that palbociclib inhibited CDK4/6 and the cell cycle initially in most patients.

The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

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Dijk, Marianne van; Murphy, Eoin [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); Morrell, Ruth [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Knapper, Steven [Department of Haematology, School of Medicine, Cardiff University, Heath Park, CF14 4XN Cardiff (United Kingdom); O' Dwyer, Michael [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Samali, Afshin; Szegezdi, Eva, E-mail: eva.szegezdi@nuigalway.ie [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)

2011-03-15

Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.

Science.gov (United States)

Zhou, Xin; Wang, Jing; Xia, Jun; Cheng, Feng; Mao, Jingjue; Zhu, Jianwei; Guo, Hongfeng

2018-01-01

The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. Complete remission (CR) was seen in 39.2% of patients with NLR analysis, only elevated LDH and IgA MM were factors predicting inferior OS. Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.

Final Results of a Phase 1 Study of Vorinostat, Pegylated Liposomal Doxorubicin, and Bortezomib in Relapsed or Refractory Multiple Myeloma.

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Voorhees, Peter M; Gasparetto, Cristina; Moore, Dominic T; Winans, Diane; Orlowski, Robert Z; Hurd, David D

2017-07-01

Deacetylase inhibitors have synergistic activity in combination with proteasome inhibitors and anthracyclines in preclinical models of multiple myeloma (MM). We therefore evaluated the safety and efficacy of the deacetylase inhibitor vorinostat in combination with pegylated liposomal doxorubicin (PLD) and bortezomib in relapsed/refractory MM. Thirty-two patients were treated with PLD and bortezomib in combination with escalating doses of vorinostat on days 4 to 11 or 1 to 14. The maximum tolerated dose of vorinostat was 400 mg on days 4 to 11. Neutropenia and thrombocytopenia attributable to protocol therapy were seen in 59% and 94% of patients, of which 37% and 47% were of grade 3 or higher severity, respectively. Constitutional and gastrointestinal adverse events of all grades were common, the majority of which were less than grade 3 in severity. The overall response rate (partial response rate or better) was 65% and the clinical benefit rate (minimal response rate or better) 74%. The overall response rate was 83%, 71%, and 45% for patients with bortezomib-naive, -sensitive, and -refractory MM, respectively. The median progression-free survival was 13.9 months and the 3-year overall survival 77%. Whole blood proteasome activity assays demonstrated a potential impact of vorinostat on the chymotryptic-like activity of the proteasome. Further evaluation of PLD, bortezomib, and deacetylase inhibitor combinations is warranted, with special attention directed toward strategies to improve tolerability. Copyright © 2017 Elsevier Inc. All rights reserved.

Bortezomib for antibody mediated rejection treatment: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City.

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Leyva, Sergio; Marino-Vázquez, Lluvia A; Reyes-Loaeza, Jorge A; Vega, Olynka; Uribe-Uribe, Norma; Alberú, Josefina; Morales-Buenrostro, Luis E

2009-01-01

The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response neither to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal.

Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

Directory of Open Access Journals (Sweden)

Denise Niewerth

2016-09-01

Full Text Available Abstract Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML and acute lymphocytic leukaemia (ALL. Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children’s Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1 and AML (COG-AAML07P1. Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12 obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Results Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001. These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028 between patients who did (n = 4 and did not reach complete remission (CR (n = 8, although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. Conclusions These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.

Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations

International Nuclear Information System (INIS)

Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh

2017-01-01

Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH 2 ) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH 2 ). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2 mM G5-PPI-NH 2 concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH 10.0, respectively (p < 0.05). The solubility of the drug was increased to a greater extent with G5-PPI-NH 2 dendrimers because it has more hydrophobic interior than G4-PAMAM-NH 2 dendrimers. The release of BTZ from G5-PPI-NH 2 complex was comparatively slower than G4-PAMAM-NH 2 . The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. - Highlights: • The present study reports the application of PAMAM and PPI dendrimers in solubilizing bortezomib with possible mechanism. • Improved solubility of bortezomib through dendrimers could significantly contribute its successful anticancer potential. • Molecular simulation and thermodynamic

Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations

Energy Technology Data Exchange (ETDEWEB)

Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh, E-mail: umeshgupta175@gmail.com

2017-03-01

Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH{sub 2}) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH{sub 2}). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2 mM G5-PPI-NH{sub 2} concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH 10.0, respectively (p < 0.05). The solubility of the drug was increased to a greater extent with G5-PPI-NH{sub 2} dendrimers because it has more hydrophobic interior than G4-PAMAM-NH{sub 2} dendrimers. The release of BTZ from G5-PPI-NH{sub 2} complex was comparatively slower than G4-PAMAM-NH{sub 2}. The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. - Highlights: • The present study reports the application of PAMAM and PPI dendrimers in solubilizing bortezomib with possible mechanism. • Improved solubility of bortezomib through dendrimers could significantly contribute its successful anticancer potential. �

Photochemical Degradation of the Anticancer Drug Bortezomib by V-UV/UV (185/254 nm) Investigated by (1)H NMR Fingerprinting: A Way to Follow Aromaticity Evolution.

Science.gov (United States)

Martignac, Marion; Balayssac, Stéphane; Gilard, Véronique; Benoit-Marquié, Florence

2015-06-18

We have investigated the removal of bortezomib, an anticancer drug prescribed in multiple myeloma, using the photochemical advanced oxidation process of V-UV/UV (185/254 nm). We used two complementary analytical techniques to follow the removal rate of bortezomib. Nuclear magnetic resonance (NMR) is a nonselective method requiring no prior knowledge of the structures of the byproducts and permits us to provide a spectral signature (fingerprinting approach). This untargeted method provides clues to the molecular structure changes and information on the degradation of the parent drug during the irradiation process. This holistic NMR approach could provide information for monitoring aromaticity evolution. We use liquid chromatography, coupled with high-resolution mass spectrometry (LC-MS), to correlate results obtained by (1)H NMR and for accurate identification of the byproducts, in order to understand the mechanistic degradation pathways of bortezomib. The results show that primary byproducts come from photoassisted deboronation of bortezomib at 254 nm. A secondary byproduct of pyrazinecarboxamide was also identified. We obtained a reliable correlation between these two analytical techniques.

iPad portable genius

CERN Document Server

McFedries, Paul

2013-01-01

Make the most of your iPad with these savvy tips and techniques The iPad, iPad Air, and iPad mini are taking the world by storm. This no-nonsense guide covers everything you want to know to take full advantage of all your iPad has to offer. Along with necessary basics about the newest iPad; iPad Air, iPad mini; and iOS; it gives you smart; innovative ways to accomplish a variety of tasks and tips to help you maximize the convenience of your Apple digital lifestyle. More than 100 million iPads have been sold; and the number continues to growHip and practical; Portable Genius guides are packed

CFD Analysis of A Starved Four-Pad Tilting-Pad Journal Bearing with An Elastic Support of Pads

Science.gov (United States)

Parovay, E. F.; Falaleev, S. V.

2018-01-01

Tilting-pad journal bearings are widely used in technics. Oil starvation operation regime is not common for hydrodynamic bearings. However, correctly designed low-flow journal bearing have to operate efficiently and consistently on high rotor speeds. An elastic support of bearing pads is a set of elastic pins made of steel. Elastic support allows pads to self-align and achieve an optimal operational mode. The article presents the thermohydrodynamic performance of an axial journal bearing. The study deals with 60 mm diameter four-pad tilting-pad journal bearing, submitted to a static load varying from 1000 to 30000 N with a rotating speed varying from 1000 to 10000 rpm. The investigation focuses on numerical studying the characteristics of low-flow tilting-pad journal bearings under oil starvation conditions. Dependencies of the bearing performance on the load, rotational speed of the shaft, and the size of the radial clearance are presented.

Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

DEFF Research Database (Denmark)

Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

2014-01-01

Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six e...

iPad for the older and wiser get up and running with your Apple iPad, iPad Air and iPad Mini

CERN Document Server

McManus, Sean

2013-01-01

Apple's iPad puts a limitless world of entertainment, communication, and everyday functionality in the palms of your hands. iPad for the Older and Wiser, 4th Edition quickly teaches you how to make the most of your new gadget with easy-to-follow instructions. Fully updated to include the iPad Air and iOS 7, this step-by-step guide shows you exactly how to set up your device and discover what it can do - all in jargon-free language. Learn how to: Set up your iPad and copy music and photos from your computerKeep in touch with email and messagesBrowse the web and shop onlineHave video chats wi

Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling

Directory of Open Access Journals (Sweden)

Fabrizio Accardi

2015-01-01

Full Text Available Multiple myeloma (MM is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB ligand (RANKL or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease.

Bortezomib for acute humoral rejection treatment at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City: an update.

Science.gov (United States)

Leyva, Sergio; Marino, Lluvia A; Alberú, Josefina; Morales-Buenrostro, Luis E

2010-01-01

The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response, or to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will be necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal. Until now, it is evident that many patients needed retreatment and they were well tolerated.

No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

International Nuclear Information System (INIS)

Vangsted, Annette J; Rasmussen, Henrik B; Søeby, Karen; Klausen, Tobias W; Abildgaard, Niels; Andersen, Niels F; Gimsing, Peter; Gregersen, Henrik; Vogel, Ulla; Werge, Thomas

2010-01-01

The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome

Impacts of iPad attributes, Lifestyles and media dependency on adoption of iPad and intensity of iPad usage in Mainland China

OpenAIRE

Kevin, Li Xinpeng

2012-01-01

The goal of this exploratory research is to identify attributes that can distinctly characterize iPad and examine the predictive power of iPad attributes, lifestyles, media dependency, and demographics on adoption of iPad, iPad usage patterns and intensity of iPad usage. Using a snowballing sample, an online survey was conducted with 623 university students in Mainland China, among which 217 were iPad users and 406 were non-users. Results of regression analyses show that application affordanc...

iPad Made Simple

CERN Document Server

Trautschold, Martin; Learning, MSL Made Simple

2010-01-01

The new iPad is sleek, powerful, and most importantly, it's much more than just a big iPhone. Your iPad is can be used for reading, surfing the web, emailing, watching TV/Movies, getting work done, and much more. And with the upcoming wave of iPad apps, the possibilities are endless. iPad X Made Simple clarifies all of the key features on the iPad, introduces what's new, and also reveals dozens of time-saving shortcuts and techniques. The book has over 1,000 screen shots that are carefully annotated with step-by-step instructions. * Clear instructions on how to set up and use the iPad * Illust

PsyPad: a platform for visual psychophysics on the iPad.

Science.gov (United States)

Turpin, Andrew; Lawson, David J; McKendrick, Allison M

2014-03-11

This article introduces PsyPad, a customizable, open-source platform for configuring and conducting visual psychophysics experiments on iPads without the need for any code development for the iPad. Stimuli for experiments are created off-line as a library of images. The PsyPad app (obtainable from the Apple App Store) presents the images according to either built-in, customizable staircase or method of constant stimuli procedures, mapping stimuli levels to images based on the image file names. On-screen buttons for responses are configurable and matched to "correct" using the image file name of any given stimulus. All actions are logged into a text file and sent to a specified server at the end of the test if an Internet connection is available. If the iPad is not connected, the results are uploaded the next time the iPad is online. We provide a secure server for this purpose, but the server-side software is also open source if researchers choose to run their own server.

TypePad For Dummies

CERN Document Server

Nelson, Melanie

2010-01-01

TypePad for Dummies will be on guiding readers through the technical tasks necessary for starting, using and customizing a TypePad blog. It will comprehensively explain choosing the right TypePad membership plan, singing up, configuring, using and customizing a blog using the TypePad system. It will also include: Illustrations from real-world blogs with screenshots and specific examples that bring the book's concepts and ideas to life.; Step-by-step tutorials that will walk readers through the process of signing up for a new TypePad blog and getting down the business of publishing their conten

iPad Portable Genius

CERN Document Server

McFedries, Paul

2010-01-01

Everything everyone wants to know about using the Apple iPad. On January 27, 2010, Apple announced the latest in its line of revolutionary, ultraportable devices - the iPad. iPad Portable Genius is the latest in a line of ultra handy, go-to and goes-with you anywhere guides for getting the most out of a new Apple product. Written to provide readers with highly useful information that's easily accessible, iPad Portable Genius is full of tips, tricks and techniques for maximizing each of the iPad's most popular features.:; Designed in full-color with an Apple look and feel, and written in a hip,

Teaching with iPads

Science.gov (United States)

Maj, Hubert

2015-04-01

Bilingual students in high school with bilingual units in Boguchwała have received iPads for learning English and a few subjects using CLIL (biology, basics of entrepreneurship, geography, IT and mathematics). Lessons with iPads are interesting for students for several reasons. First of all, teenagers like new technologies and using iPads for teaching helps students to learn by fun. Secondly, iPads give new possibilities of looking for knowledge about each theme. Moreover, teaching with iPads develops students' engagement. They have a chance to choose a few among over 65 000 applications for gathering and then presenting information about the lesson topic. They can easily prepare presentations, movies, cartoons, mind maps or whatever they like. Teaching students, thanks to the iPads, makes it their initiative, and the teacher can inspire them to look for the knowledge rather than disciplining pupils. But teaching with iPads is connected with many problems. For instance, there are not any examples on how to teach using these tools. It is very up-to-date technology and teachers firstly must learn the possibilities of iPads and look for new applications. It takes much time, especially at the beginning, and is difficult especially for inexperienced teachers. In addition, it is almost impossible to maintain control of the iPads for all of the students during the lesson. They can use their iPads for something unconnected with the topic of the lesson. Thirdly is lack of time - active methods (with iPads as well) are more time-consuming and it could be that they do not finish the whole program. And of course the last, but not at least, is the problem of money. Some of the applications must be paid for, and it is usually obligatory to possess a credit card. Fortunately, it is not expensive - applications usually cost a few euros and many of them are free and really good.

Vorinostat in combination with bortezomib in patients with advanced malignancies directly alters transcription of target genes.

Science.gov (United States)

Kolesar, Jill M; Traynor, Anne M; Holen, Kyle D; Hoang, Tien; Seo, Songwon; Kim, Kyungmann; Alberti, Dona; Espinoza-Delgado, Igor; Wright, John J; Wilding, George; Bailey, Howard H; Schelman, William R

2013-09-01

Vorinostat is a small molecule inhibitor of class I and II histone deacetylase enzymes which alters the expression of target genes including the cell cycle gene p21, leading to cell cycle arrest and apoptosis. Patients enrolled in a phase I trial were treated with vorinostat alone on day 1 and vorinostat and bortezomib in combination on day 9. Paired biopsies were obtained in eleven subjects. Blood samples were obtained on days 1 and 9 of cycle 1 prior to dosing and 2 and 6 h post-dosing in all 60 subjects. Gene expression of p21, HSP70, AKT, Nur77, ERB1, and ERB2 was evaluated in peripheral blood mononuclear cells and tissue samples. Chromatin immunoprecipitation of p21, HSP70, and Nur77 was also performed in biopsy samples. In peripheral blood mononuclear cells, Nur77 was significantly and consistently decreased 2 h after vorinostat administration on both days 1 and 9, median ratio of gene expression relative to baseline of 0.69 with interquartile range 0.49-1.04 (p vorinostat and bortezomib. p21, a downstream target of Nur77, was significantly decreased on day 9, 2 and 6 h after administration of vorinostat and bortezomib, 0.67 (0.41-1.03) (p vorinostat in tissue biopsies in most patients. Vorinostat inhibits Nur77 expression, which in turn may decrease p21 and AKT expression in PBMCs. The influence of vorinostat on target gene expression in tumor tissue was variable; however, most patients demonstrated interaction of acetylated H3 with Nur77, HSP70, and p21 which provides evidence of interaction with the transcriptionally active acetylated H3.

Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies

International Nuclear Information System (INIS)

Kubicek, Gregory J.; Werner-Wasik, Maria; Machtay, Mitchell; Mallon, Gayle; Myers, Thomas; Ramirez, Michael; Andrews, David; Curran, Walter J.; Dicker, Adam P.

2009-01-01

Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m 2 /dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m 2 starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributable to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m 2 /dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m 2 ) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.

Teach yourself visually iPad

CERN Document Server

Hart-Davis, Guy

2013-01-01

Fully updated coverage on the latest iPad and iPad mini! As the amazing iPad continues to evolve, so does this invaluable visual guide. Bestselling veteran author Guy Hart-Davis gets you up to date on the latest generation of the iPad, the new iPad Air, as well as the iPad mini with his clear step-by-step, image-driven guidance that is perfectly geared towards those who learn best with visual assistance. You'll get all the latest information for accessing and downloading books, apps, music, and video content as well as sending photos and e-mails, syncing with other devices and services, and

Abdominal wall fat pad biopsy

Science.gov (United States)

Amyloidosis - abdominal wall fat pad biopsy; Abdominal wall biopsy; Biopsy - abdominal wall fat pad ... is the most common method of taking an abdominal wall fat pad biopsy . The health care provider cleans the ...

Expression of TRIM28 correlates with proliferation and Bortezomib-induced apoptosis in B-cell non-Hodgkin lymphoma.

Science.gov (United States)

Zhang, Pei-Pei; Ding, Da-Zhi; Shi, Bing; Zhang, Shu-Qing; Gu, Ling-Li; Wang, Yu-Chan; Cheng, Chun

2018-03-23

Tripartite motif containing 28 (TRIM28) as a transcriptional co-repressor has been reported playing a role in regulating DNA damage response (DDR), cell differentiation, immune response, and tumorigenesis. The present study was performed to explore the biological function and clinical significance of TRIM28 in B-cell non-Hodgkin lymphoma (B-NHL). Results of the study displayed that high expression of TRIM28 was positively associated with the poorer survival of B-NHL patients as an independent prognostic factor. In addition, TRIM28 could promote the B-NHL cells proliferation through modulating cell cycle progression. The change of cyclinA, P21, and PCNA expression after TRIM28 expression modified further illustrated the mechanism in which TRIM28 participated in cell proliferation progression. Moreover, inhibition TRIM28 expression in B-NHL cells enhanced the sensibility to Bortezomib by regulating p53-mediated apoptosis pathway. Taken together, the present study showed that TRIM28 functions as a tumor promoter in B-NHL and may be a novel target for drug resistance to Bortezomib.

Analysis of two commercially available bortezomib products: differences in assay of active agent and impurity profile.

Science.gov (United States)

Byrn, Stephen R; Tishmack, Patrick A; Milton, Mark J; van de Velde, Helgi

2011-06-01

The analytical properties of two commercially available bortezomib products (VELCADE(®) and Bortenat) were compared using nuclear magnetic resonance, mass spectrometry, high-performance liquid chromatography, and gas chromatography. The data showed differences between the two products. Based on these data, Bortenat samples contained more active ingredients than indicated by the label (mean, 116.5% and 117.9% of label, in 2-mg and 3.5-mg vials, respectively). In comparison, VELCADE samples contained a mean of 99.3% of active ingredient, which was consistent with the approved specification range (US, 90-110%; EU, 95-105%). Clinical data demonstrate that patients exposed to higher than recommended doses of bortezomib on the standard twice-weekly dosing schedule are likely to have an increased risk of major toxicities. Bortenat 2-mg vials contained an isovaleraldehyde impurity; the origin of this is unknown. Additionally, the ratio of boronic acid to boronic ester differed between Bortenat 2 mg (0.27:1) and 3.5 mg (0.13:1) and VELCADE (0.10:1) samples reconstituted in saline indicating that the Bortenat product is not equivalent to the VELCADE product.

Dynamic behavior of air lubricated pivoted-pad journal-bearing, rotor system. 2: Pivot consideration and pad mass

Science.gov (United States)

Nemeth, Z. N.

1972-01-01

Rotor bearing dynamic tests were conducted with tilting-pad journal bearings having three different pad masses and two different pivot geometries. The rotor was vertically mounted and supported by two three-pad tilting-pad gas journal bearings and a simple externally pressurized thrust bearing. The bearing pads were 5.1 cm (2.02 in.) in diameter and 2.8 cm (1.5 in.) long. The length to diameter ratio was 0.75. One pad was mounted on a flexible diaphragm. The bearing supply pressure ranged from 0 to 690 kilonewtons per square meter (0 to 100 psig), and speeds ranged to 38,500 rpm. Heavy mass pad tilting-pad assemblies produced three rotor-bearing resonances above the first two rotor critical speeds. Lower supply pressure eliminated the resonances. The resonances were oriented primarily in the direction normal to the diaphragm.

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.

Science.gov (United States)

García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia

2017-12-01

Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.

iPad 2 Made Simple

CERN Document Server

Mazo, Gary; Ritchie, Rene

2011-01-01

The iPad 2 is thinner, more powerful, intuitive and very fun for users of all ages. Your iPad can be used for reading, surfing the web, emailing, watching TV and movies, getting work done and much more. And with over 65,000 apps just for the iPad, as well as the ability to run over 30,000 iPhone apps, the possibilities are endless. iPad 2 Made Simple clarifies all of the key features on the iPad, introduces what's new, and also reveals dozens of time-saving shortcuts and techniques. The book has over 1,000 screen shots that are carefully annotated with step-by-step instructions. * Clear instru

BTK inhibitor ibrutinib is cytotoxic to myeloma and potently enhances bortezomib and lenalidomide activities through NF-κB.

Science.gov (United States)

Rushworth, Stuart A; Bowles, Kristian M; Barrera, Lawrence N; Murray, Megan Y; Zaitseva, Lyubov; MacEwan, David J

2013-01-01

Ibrutinib (previously known as PCI-32765) has recently shown encouraging clinical activity in chronic lymphocytic leukaemia (CLL) effecting cell death through inhibition of Bruton's tyrosine kinase (BTK). In this study we report for the first time that ibrutinib is cytotoxic to malignant plasma cells from patients with multiple myeloma (MM) and furthermore that treatment with ibrutinib significantly augments the cytotoxic activity of bortezomib and lenalidomide chemotherapies. We describe that the cytotoxicity of ibrutinib in MM is mediated via an inhibitory effect on the nuclear factor-κB (NF-κB) pathway. Specifically, ibrutinib blocks the phosphorylation of serine-536 of the p65 subunit of NF-κB, preventing its nuclear translocation, resulting in down-regulation of anti-apoptotic proteins Bcl-xL, FLIP(L) and survivin and culminating in caspase-mediated apoptosis within the malignant plasma cells. Taken together these data provide a platform for clinical trials of ibrutinib in myeloma and a rationale for its use in combination therapy, particularly with bortezomib. Copyright © 2012 Elsevier Inc. All rights reserved.

Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib.

Science.gov (United States)

Neeson, Paul J; Hsu, Andy K; Chen, Yin R; Halse, Heloise M; Loh, Joanna; Cordy, Reece; Fielding, Kate; Davis, Joanne; Noske, Josh; Davenport, Alex J; Lindqvist-Gigg, Camilla A; Humphreys, Robin; Tai, Tsin; Prince, H Miles; Trapani, Joseph A; Smyth, Mark J; Ritchie, David S

2015-09-01

There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune response. In this study, we used the novel combination of agonistic anti-TRAIL-R1 antibody (mapatumumab, Mapa) with low dose bortezomib (LDB) for this purpose. The combination induced profound myeloma cell apoptosis, greatly enhanced the uptake of myeloma cell apoptotic bodies by dendritic cell (DC) and induced anti-myeloma cytotoxicity by both CD8 + T cells and NK cells. Cytotoxic lymphocyte expansion was detected within 24 h of commencing therapy and was maximized when myeloma-pulsed DC were co-treated with low dose bortezomib and mapatumumab (LDB+Mapa) in the presence of NK cells. This study shows that Mapa has two distinct but connected modes of action against multiple myeloma (MM). First, when combined with LDB, Mapa produced powerful myeloma cell apoptosis; secondly, it promoted DC priming and an NK cell-mediated expansion of anti-myeloma cytotoxic lymphocyte (CTL). Overall, this study indicates that Mapa can be used to drive potent anti-MM immune responses.

Treating P.A.D.

Science.gov (United States)

... Issue Past Issues Special Section Treating P.A.D. Past Issues / Summer 2008 Table of Contents For ... Illustration courtesy of NHLBI Treatment for P.A.D. is designed to reduce a patient's symptoms, prevent ...

Functionally different pads on the same foot allow control of attachment: stick insects have load-sensitive "heel" pads for friction and shear-sensitive "toe" pads for adhesion.

Directory of Open Access Journals (Sweden)

David Labonte

Full Text Available Stick insects (Carausius morosus have two distinct types of attachment pad per leg, tarsal "heel" pads (euplantulae and a pre-tarsal "toe" pad (arolium. Here we show that these two pad types are specialised for fundamentally different functions. When standing upright, stick insects rested on their proximal euplantulae, while arolia were the only pads in surface contact when hanging upside down. Single-pad force measurements showed that the adhesion of euplantulae was extremely small, but friction forces strongly increased with normal load and coefficients of friction were [Formula: see text] 1. The pre-tarsal arolium, in contrast, generated adhesion that strongly increased with pulling forces, allowing adhesion to be activated and deactivated by shear forces, which can be produced actively, or passively as a result of the insects' sprawled posture. The shear-sensitivity of the arolium was present even when corrected for contact area, and was independent of normal preloads covering nearly an order of magnitude. Attachment of both heel and toe pads is thus activated partly by the forces that arise passively in the situations in which they are used by the insects, ensuring safe attachment. Our results suggest that stick insect euplantulae are specialised "friction pads" that produce traction when pressed against the substrate, while arolia are "true" adhesive pads that stick to the substrate when activated by pulling forces.

Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

Directory of Open Access Journals (Sweden)

Britta Stadelmann

2014-12-01

Full Text Available A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ, a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

iPad for digital photographers

CERN Document Server

Story, Derrick

2013-01-01

Discover innovative ways to strengthen your photography business with your iPad Many photographers are turning to the flexible, easy-to-use tools of the iPad and relying on them to wear a variety of hats in their photography business. Whether portable portfolio, editing tool, payment-tracking system, or appointment calendar, the iPad melds together the best attributes of the cell phone and a laptop computer and this unique book highlights them all. With this helpful resource, you'll learn how to get the most out of your iPad to not only improve your business but also enhance your p

Analysis of Two Commercially Available Bortezomib Products: Differences in Assay of Active Agent and Impurity Profile

OpenAIRE

Byrn, Stephen R.; Tishmack, Patrick A.; Milton, Mark J.; van de Velde, Helgi

2011-01-01

The analytical properties of two commercially available bortezomib products (VELCADE® and Bortenat) were compared using nuclear magnetic resonance, mass spectrometry, high-performance liquid chromatography, and gas chromatography. The data showed differences between the two products. Based on these data, Bortenat samples contained more active ingredients than indicated by the label (mean, 116.5% and 117.9% of label, in 2-mg and 3.5-mg vials, respectively). In comparison, VELCADE samples conta...

Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations.

Science.gov (United States)

Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh

2017-03-01

Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH 2 ) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH 2 ). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2mM G5-PPI-NH 2 concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH10.0, respectively (pdendrimers because it has more hydrophobic interior than G4-PAMAM-NH 2 dendrimers. The release of BTZ from G5-PPI-NH 2 complex was comparatively slower than G4-PAMAM-NH 2 . The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

iPad mini for dummies

CERN Document Server

Baig, Edward C

2014-01-01

Find out why the iPad mini has never been bigger This new edition of iPad mini For Dummies covers all the latest tips and tricks for getting an even bigger bang out of your iPad mini. Presented in full-color and written in the straightforward but fun language that has defined the For Dummies brand for more than twenty years, this friendly guide walks you through the multitouch interface, going online, getting connected, packing your iPad mini with apps, games, e-books, photos, music, and movies, synchronizing your data, texting with iMessage, working with Siri, importing pictures and launching

Beginning iPad Application Development

CERN Document Server

Lee, Wei-Meng

2010-01-01

A hands-on approach to iPad application development. Beginning iPad Application Development is written to help jumpstart beginning iPad developers. It covers the various topics in such a manner that you will progressively learn without being overwhelmed by the details. It adopts the philosophy that the best way to learn is by doing, hence the numerous Try It Out sections in all the chapters, which first show you how to build something and then explain how things work. Although iPad programming is a huge topic, the aim for this book is to get you started with the fundamentals, and help you unde

iPad & Siri for dummies

CERN Document Server

Baig, Edward C

2012-01-01

Two complete e-books on using iPad and Siri for one low price! This unique value-priced e-book set brings together two bestselling For Dummies books in a single e-book file. Including a comprehensive table of contents and the full text of each book, complete with cover, this e-book set helps you get the most out of your iPad and Siri, its artificial intelligence personal assistant. Best of all, you'll pay less than the cost of each book purchased separately. You'll get the complete text of: iPad For Dummies, which helps you toSet up your iPad, browse the

Activation of PAD4 in NET formation

Directory of Open Access Journals (Sweden)

Amanda eRohrbach

2012-11-01

Full Text Available Peptidyl arginine deiminases, or PADs, convert arginine residues to the non-ribosomally encoded amino acid citrulline in a variety of protein substrates. PAD4 is expressed in granulocytes and is essential for the formation of neutrophil extracellular traps (NETs via PAD4-mediated histone citrullination. Citrullination of histones is thought to promote NET formation by inducing chromatin decondensation and facilitating the expulsion of chromosomal DNA that is coated with antimicrobial molecules. Numerous stimuli have been reported to lead to PAD4 activation and NET formation. However, how this signaling process proceeds and how PAD4 becomes activated in cells is largely unknown. Herein, we describe the various stimuli and signaling pathways that have been implicated in PAD4 activation and NET formation, including the role of reactive oxygen species generation. To provide a foundation for the above discussion, we first describe PAD4 structure and function, and how these studies led to the development of PAD-specific inhibitors. A comprehensive survey of the receptors and signaling pathways that regulate PAD4 activation will be important for our understanding of innate immunity, and the identification of signaling intermediates in PAD4 activation may also lead to the generation of pharmaceuticals to target NET-related pathogenesis.

Classifying insulin regimens

DEFF Research Database (Denmark)

Neu, A; Lange, K; Barrett, T

2015-01-01

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...

Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.

Science.gov (United States)

Botta, Cirino; Ciliberto, Domenico; Rossi, Marco; Staropoli, Nicoletta; Cucè, Maria; Galeano, Teresa; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

2017-02-28

Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included in the NMA. Pairwise meta-analyses showed that a 3-drug regimen (bortezomib- or IMiD-based) was superior to a 2-drug regimen in progression-free-survival (PFS) and overall response rate (ORR). NMA showed that an IMiD backbone associated with anti-MM monoclonal antibodies (mAbs) (preferably) or proteasome inhibitors had the highest probability of being the most effective regimen with the lowest toxicity. The combination of daratumumab, lenalidomide, and dexamethasone ranked as the first regimen in terms of activity, efficacy, and tolerability according to the average value between surface under the cumulative ranking curve of PFS, overall survival, ORR, complete response rate, and safety. This is the first NMA comparing all currently available regimens evaluated in published randomized trials for the treatment of RRMM, but our results need to be interpreted taking into account differences in their patient populations. Our analysis suggests that IMiDs plus new anti-MM mAb-containing regimens are the most active therapeutic option in RRMM.

Experienced iPad-Using Early Childhood Teachers: Practices in the One-to-One iPad Classroom

Science.gov (United States)

Lu, Ya-Huei; Ottenbreit-Leftwich, Anne T.; Ding, Ai-Chu; Glazewski, Krista

2017-01-01

Although many elementary schools have adopted one-to-one programs, we still lack information on how teachers integrate iPads or other tablets into their daily instruction, especially in early childhood settings. The purpose of this case study was to present how four experienced iPad-using early childhood teachers integrated one-to-one iPads into…

iPad for the Older and Wiser Get Up and Running Safely and Quickly with the Apple iPad

CERN Document Server

McManus, Sean

2011-01-01

Easy-to-follow, friendly advice on using the iPad 2 This heavily illustrated, approachable guide for the anyone over 50 provides a solid resource for learning how to use the iPad in everyday situations. Veteran author and technology expert Sean McManus clearly explains how to use the iPad to send e-mails, listen to music, watch movies, and play games. Detailed coverage walks you step by step through setting up and registering your iPad, connecting to the Internet, syncing your iPad to other devices, and much more. The iPad is an ideal companion for making your life easier, and this friendly gu

iPads og undervisningsdifferentiering

DEFF Research Database (Denmark)

Lorentzen, Rasmus Fink

2013-01-01

Artiklen er blevet til på baggrund af udviklingsprojektet med iPad i Odder Kommune. Den generaliserer på baggrund af en række eksempler herfra og peger på at med iPad'en drejer det sig om at udnytte mulighederne for at lade eleverne arbejde producerende, kollaborativt og fagligt meningsfuldt...

TPC cathode read-out with C-pads

International Nuclear Information System (INIS)

Janik, R.; Pikna, M.; Sitar, B.; Strmen, P.; Szarka, I.

2009-01-01

A Time Projection Chamber with 'C' like shaped cathode pads was built and tested. It offers a low gas gain operation, a good pulse shape and a lightweight construction. The Pad Response Function (PRF), the cathode to anode pulse height ratios and the pad pulse shapes of the C-pad structure were measured and compared with planar cathode structures in two different wire geometries. The cathode to anode signal ratio was improved from between 0.2 and 0.4 up to 0.7. The PRF was considerably improved, it has a Gaussian shape and is narrower than in the case of the planar pads. The pulse shape from the C-pad read-out is similar to the pulse shape from a detector with a cylindrical shape of electrodes. A method for aluminum pad mass production based on a precise cold forging was developed and tested.

21 CFR 878.4440 - Eye pad.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Eye pad. 878.4440 Section 878.4440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4440 Eye pad. (a) Identification. An eye pad is...

Treatment of Antibody-Mediated Renal Allograft Rejection: Improving Step by Step

Directory of Open Access Journals (Sweden)

Nils Lachmann

2017-01-01

Full Text Available Throughout the past years we stepwise modified our immunosuppressive treatment regimen for patients with antibody-mediated rejection (ABMR. Here, we describe three consecutive groups treated with different regimens. From 2005 until 2008, we treated all patients with biopsy-proven ABMR with rituximab (500 mg, low-dose (30 g intravenous immunoglobulins (IVIG, and plasmapheresis (PPH, 6x (group RLP, n=12. Between 2009 and June 2010, patients received bortezomib (1.3 mg/m2, 4x together with low-dose IVIG and PPH (group BLP, n=11. In July 2010, we increased the IVIG dose and treated all subsequent patients with bortezomib, high-dose IVIG (1.5 g/kg, and PPH (group BHP, n=11. Graft survival at three years after treatment was 73% in group BHP as compared to 45% in group BLP and 25% in group RLP. At six months after treatment median serum creatinine was 2.1 mg/dL, 2.9 mg/dL, and 4.2 mg/dL in groups BHP, BLP, and RLP, respectively (p=0.02. Following treatment, a significant decrease of donor-specific HLA antibody (DSA mean fluorescence intensity from 8467±6876 to 5221±4711 (p=0.01 was observed in group BHP, but not in the other groups. Our results indicate that graft survival, graft function, and DSA levels could be improved along with stepwise modifications to our treatment regimen, that is, the introduction of bortezomib and high-dose IVIG treatment.

iPad all-in-one for dummies

CERN Document Server

Muir, Nancy C

2012-01-01

Six minibooks in one show you how to power-use the iPad For work, play, and life on the road, the iPad has quickly become indispensable, and the new iPad is packed with even more features and power than ever. In this fun and practical guide, long-time For Dummies author Nancy C. Muir walks you through the latest functions, features, and capabilities of the iPad. Get up to speed on the basics, see how to use your iPad to get more organized and productive, learn to use your iPad for work, and discover all the ways to have fun. This book covers it all, and in full color! Packs six minibooks in on

Cosmological applications of Padé approximant

International Nuclear Information System (INIS)

Wei, Hao; Yan, Xiao-Peng; Zhou, Ya-Nan

2014-01-01

As is well known, in mathematics, any function could be approximated by the Padé approximant. The Padé approximant is the best approximation of a function by a rational function of given order. In fact, the Padé approximant often gives better approximation of the function than truncating its Taylor series, and it may still work where the Taylor series does not converge. In the present work, we consider the Padé approximant in two issues. First, we obtain the analytical approximation of the luminosity distance for the flat XCDM model, and find that the relative error is fairly small. Second, we propose several parameterizations for the equation-of-state parameter (EoS) of dark energy based on the Padé approximant. They are well motivated from the mathematical and physical points of view. We confront these EoS parameterizations with the latest observational data, and find that they can work well. In these practices, we show that the Padé approximant could be an useful tool in cosmology, and it deserves further investigation

Cosmological applications of Padé approximant

Science.gov (United States)

Wei, Hao; Yan, Xiao-Peng; Zhou, Ya-Nan

2014-01-01

As is well known, in mathematics, any function could be approximated by the Padé approximant. The Padé approximant is the best approximation of a function by a rational function of given order. In fact, the Padé approximant often gives better approximation of the function than truncating its Taylor series, and it may still work where the Taylor series does not converge. In the present work, we consider the Padé approximant in two issues. First, we obtain the analytical approximation of the luminosity distance for the flat XCDM model, and find that the relative error is fairly small. Second, we propose several parameterizations for the equation-of-state parameter (EoS) of dark energy based on the Padé approximant. They are well motivated from the mathematical and physical points of view. We confront these EoS parameterizations with the latest observational data, and find that they can work well. In these practices, we show that the Padé approximant could be an useful tool in cosmology, and it deserves further investigation.

MuPAD tutorial

CERN Document Server

Creutzig, Christopher

2004-01-01

This book explains the basic use of the software package called MuPAD and gives an insight into the power of the system. MuPAD is a so-called com­ puter algebra system, which is developed mainly by Sciface Software and the MuPAD Research Group of the University of Paderborn in Germany. This introduction addresses mathematicians, engineers, computer scientists, natural scientists and, more generally, all those in need of mathematical com­ putations for their education or their profession. Generally speaking, this book addresses anybody who wants to use the power of a modern computer algebra package. There are two ways to use a computer algebra system. On the one hand, you may use the mathematical knowledge it incorporates by calling system functions interactively. For example, you can compute symbolic integrals or generate and invert matrices by calling appropriate functions. They comprise the system's mathematical intelligence and may implement sophisticated al­ gorithms. Chapters 2 through 15 discuss this...

Thermal Characterisation of Brake Pads

DEFF Research Database (Denmark)

Ramousse, Séverine; Høj, Jakob Weiland; Sørensen, O. T.

2001-01-01

The chemical-physical decomposition processes that occur in a brake pad heated to 1000degreesC have been studied. This temperature can be reached when a brake pad is applied. Thermogravimetry and differential thermal analysis were used in combination with evolved gas analysis, and image analysis...... using a scanning electron microscope.A brake pad is essentially a mixture of iron, carbon and binder. Combined techniques have been used, because of chemical reaction overlap, to determine how and at what temperature the binder decomposes, the coal and graphite combust and the iron oxidises.This work...

iPads in the Classrooms of Schools

DEFF Research Database (Denmark)

Khalid, Md. Saifuddin; Guttesen, Petur Elias Askham

2016-01-01

There is a need for emphasizing on the technological functionalities, pedagogical designs for learning, and barriers to the integration of iPads to inform the resistant teachers, school leaders, parents, and other stakeholders. This paper systematically reviews existing literature on iPads in the......There is a need for emphasizing on the technological functionalities, pedagogical designs for learning, and barriers to the integration of iPads to inform the resistant teachers, school leaders, parents, and other stakeholders. This paper systematically reviews existing literature on i...... categories: 1) functionalities and conveniences in use, 2) iPad motivates, scaffolds learning process, and instills creative problem-solving skills, 3) mobile and multi-contextual, 4) digital content creation and consumption as 21st century skills, 5) barriers to the integration and adoption of iPad, and 6......) scope of future research. There is a dearth of research focusing on the iPad-integrated pedagogical design of subject-specific lessons. This study suggests emphasizing on iPad-integrated pedagogical methods and techniques for subject-specific and app-appropriated learning activity design...

iPad all-in-one for dummies

CERN Document Server

Muir, Nancy C

2015-01-01

For iPad users who want more information than the basics of the iPad,  iPad All-in-One For Dummies provides the goods! Based on Apple's new iOS software, which includes Siri for iPad, new and improved maps with turn by turn directions, shared photo streams, Facebook integration, Passbook, FaceTime video calls over cellular, new calling features such as instant text reply and callback reminders, improved email with a VIP inbox, iCloud browsing tabs, and much more. The book is organized into the following minibooks: iPad Basics - Covers basic functionality, synching with your computer and getti

iPad 2 The Missing Manual

CERN Document Server

Biersdorfer, JD

2011-01-01

With iOS 5, Apple added more than 200 new features to the iPad 2, but there's still no printed guide to using all its amazing capabilities. That's where this full-color Missing Manual comes in. You'll learn how to stuff your iPad with media, organize your personal life, wirelessly stream content to and from your tablet, stay connected to friends, and much more. The important stuff you need to know: Build your media library. Fill your iPad with music, movies, TV shows, eBooks, eMagazines, photos, and more.Go wireless. Sync content between your computer and iPad-no wires needed.Get online. Con

Dynamic characteristics of polymer faced tilting pad journal bearings

DEFF Research Database (Denmark)

Simmons, Gregory F.; Cerda Varela, Alejandro Javier; Santos, Ilmar

2014-01-01

Dynamic characteristics of polymer faced tilting pad journal bearings are presented. Investigations are conducted using a single pad, load on pad configuration over a range of shaft speeds and loads. Two polyether ether ketone (PEEK) faced pads, one polytetrafluoroethylene (PTFE) faced pad and two...

The European Medicines Agency Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and/or Refractory Multiple Myeloma.

Science.gov (United States)

Tzogani, Kyriaki; van Hennik, Paula; Walsh, Ita; De Graeff, Pieter; Folin, Annika; Sjöberg, Jan; Salmonson, Tomas; Bergh, Jonas; Laane, Edward; Ludwig, Heinz; Gisselbrecht, Christian; Pignatti, Francesco

2017-11-30

On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. The recommended starting dose of panobinostat is 20 mg, taken orally in a cyclical manner for up to 48 weeks.The use of panobinostat in combination with bortezomib and dexamethasone was studied in a randomized, double-blind, placebo-controlled, multicenter phase III study (PANORAMA I) in 768 patients with relapsed or relapsed and refractory multiple myeloma who had received one to three prior lines of therapies. In the subgroup of patients who have received at least two prior regimens including bortezomib and an IMiD, there was a difference of 7.8 months in the progression-free survival in favor of the experimental arm (12.5 months for panobinostat + bortezomib + dexamethasone vs. 4.7 months for placebo + bortezomib + dexamethasone; hazard ratio = 0.47, 95% confidence interal 0.31-0.72; log-rank p value = .0003). The incidence of grade 3-4 adverse events suspected to be related to study drug was 76.9% vs. 51.2%, for the panobinostat and the placebo group, respectively. The most common side effects (grade 3-4) associated with panobinostat included diarrhea (18.9%), fatigue (14.7%), nausea (4.5%), vomiting (5.5%), thrombocytopenia (43.6%), anemia (7

Bortezomib modulates CHIT1 and YKL40 in monocyte-derived osteoclast and in myeloma cells.

Science.gov (United States)

Tibullo, Daniele; Di Rosa, Michelino; Giallongo, Cesarina; La Cava, Piera; Parrinello, Nunziatina L; Romano, Alessandra; Conticello, Concetta; Brundo, Maria V; Saccone, Salvatore; Malaguarnera, Lucia; Di Raimondo, Francesco

2015-01-01

Osteolytic bone disease is a common manifestation of multiple myeloma (MM) that leads to progressive skeleton destruction and is the most severe cause of morbidity in MM patients. It results from increased osteolytic activity and decrease osteoblastic function. Activation of mammalian chitinases chitotriosidase (CHIT1) and YKL40 is associated with osteoclast (OCs) differentiation and bone digestion. In the current study, we investigated the effect of two Bortezomib's concentration (2.5 and 5 nM) on osteoclastogenesis by analyzing regulation of chitinase expression. OCs exposition to bortezomib (BO) was able to inhibit the expression of different OCs markers such as RANK, CTSK, TRAP, and MMP9. In addition BO-treatment reduced CHIT1 enzymatic activity and both CHIT1 and YKL40 mRNA expression levels and cytoplasmatic and secreted protein. Moreover, immunofluorescence evaluation of mature OCs showed that BO was able to translocate YKL40 into the nucleus, while CHIT1 remained into the cytoplasm. Since MM cell lines such as U266, SKM-M1 and MM1 showed high levels of CHIT1 activity, we analyzed bone resorption ability of U266 using dentin disk assay resorption pits. Silencing chitinase proteins in U266 cell line with specific small interfering RNA, resulted in pits number reduction on dentine disks. In conclusion, we showed that BO decreases osteoclastogenesis and reduces bone resorption in OCs and U266 cell line by modulating the chitinases CHIT1 and YKL40. These results indicate that chitinases may be a therapeutic target for bone disease in MM patients.

iPad application development for dummies

CERN Document Server

Goldstein, l

2012-01-01

The fun and easy guide to creating iPad apps, updated for iOS 5! iPad app development is hot, with more than 140,000 apps available specifically for the device and that number growing every day. The introduction of iOS 5 and iCloud gives developers even more options to create incredible iPad apps. This fast and friendly guide to iPad app development is fully updated for the most recent upgrades and covers everything you need to know, starting with how to download the SDK and become an Apple developer all the way to finishing up your app and submitting it to the App Store. Zeroes in on essentia

Pericruciate fat pad of the knee: anatomy and pericruciate fat pad inflammation: cadaveric and clinical study emphasizing MR imaging

International Nuclear Information System (INIS)

Skaf, Abdalla Youssef; Hernandez Filho, Guinel; Dirim, Berna; Wangwinyuvirat, Mani; Trudell, Debra; Resnick, Donald; Haghigi, Parvitz

2012-01-01

The pericruciate fat pad is located in the intercondylar fossa, intimate with the cruciate ligaments. With MR imaging, signal abnormality of the pericruciate fat pad has been observed in patients with posterior knee pain. The purpose of this study was to describe the anatomy of the pericruciate fat pad in cadaveric specimens and to document the clinical spectrum of pericruciate fat pad inflammation. Twelve cadaveric knees underwent MR imaging with T1 and T2 multiplanar images. Cadaveric sections were then prepared for macroscopic evaluation, with additional histologic analysis performed in four cases. MR images in seventeen patients (ten males, seven females; average age, 31.5 years; age range, 19-57 years) involved in intensive sporting activity and with posterior knee pain were reviewed. MR images in cadaveric specimens showed a fat pad that was located above and between the cruciate ligaments, near their attachment sites in the inner portion of the femoral condyles, within the intercondylar fossa. Fatty tissue covered by a thin layer of synovial membrane was confirmed at histology. Seventeen patients with posterior knee pain and without gross cartilage, meniscal, or ligamentous abnormalities all revealed an increased signal in this fat pad in fluid-sensitive fat-suppressed images, mainly in the sagittal and axial planes. In eight cases, enhancement of this fat pad was demonstrated following intravenous gadolinium administration. The pericruciate fat pad is a structure located in the intercondylar fossa, intimate with both the anterior and posterior cruciate ligaments. Inflammatory changes in this fat pad may be found in patients, especially athletes with posterior knee pain. (orig.)

Pericruciate fat pad of the knee: anatomy and pericruciate fat pad inflammation: cadaveric and clinical study emphasizing MR imaging

Energy Technology Data Exchange (ETDEWEB)

Skaf, Abdalla Youssef [Hospital do Coracao (HCor), Department of Radiology, Sao Paulo, SP (Brazil); Hernandez Filho, Guinel [Santa Casa de Sao Paulo Hospital, Department of Radiology, Sao Paulo, SP (Brazil); Dirim, Berna [Izmir Atatuerk Training and Research Hospital, Department of Radiology, Karsiyaka, izmir (Turkey); Wangwinyuvirat, Mani [Rajavithi Hospital, Department of Radiology, Bangkok (Thailand); Trudell, Debra; Resnick, Donald [University of California, San Diego, Department of Radiology, Veterans Affairs Medical Center, La Jolla, CA (United States); Haghigi, Parvitz [University of California, San Diego, Department of Pathology, Veterans Affairs Medical Center, La Jolla, CA (United States)

2012-12-15

The pericruciate fat pad is located in the intercondylar fossa, intimate with the cruciate ligaments. With MR imaging, signal abnormality of the pericruciate fat pad has been observed in patients with posterior knee pain. The purpose of this study was to describe the anatomy of the pericruciate fat pad in cadaveric specimens and to document the clinical spectrum of pericruciate fat pad inflammation. Twelve cadaveric knees underwent MR imaging with T1 and T2 multiplanar images. Cadaveric sections were then prepared for macroscopic evaluation, with additional histologic analysis performed in four cases. MR images in seventeen patients (ten males, seven females; average age, 31.5 years; age range, 19-57 years) involved in intensive sporting activity and with posterior knee pain were reviewed. MR images in cadaveric specimens showed a fat pad that was located above and between the cruciate ligaments, near their attachment sites in the inner portion of the femoral condyles, within the intercondylar fossa. Fatty tissue covered by a thin layer of synovial membrane was confirmed at histology. Seventeen patients with posterior knee pain and without gross cartilage, meniscal, or ligamentous abnormalities all revealed an increased signal in this fat pad in fluid-sensitive fat-suppressed images, mainly in the sagittal and axial planes. In eight cases, enhancement of this fat pad was demonstrated following intravenous gadolinium administration. The pericruciate fat pad is a structure located in the intercondylar fossa, intimate with both the anterior and posterior cruciate ligaments. Inflammatory changes in this fat pad may be found in patients, especially athletes with posterior knee pain. (orig.)

Successful use of combined high cut-off haemodialysis and bortezomib for acute kidney injury associated with myeloma cast nephropathy.

LENUS (Irish Health Repository)

Ward, F

2012-05-01

We present the case of a 58-year old female with de novo dialysis-dependent acute kidney injury (AKI) secondary to myeloma cast nephropathy. The patient underwent extended high cut-off haemodialysis (HCO-HD), in conjunction with bortezomib-based chemotherapy, and soon became dialysis independent with normal renal function. To our knowledge, this is the first time this treatment strategy has been employed successfully in an Irish centre.

Take control of media on your iPad

CERN Document Server

Carlson, Jeff

2011-01-01

Join media-savvy author Jeff Carlson as he helps you enjoy media on your iPad like never before. Jeff explains basic and advanced ways of adding media to your iPad, and gives you a thorough grounding in Apple's core media apps-iBooks, iPod, Videos, and Photos. He also helps you integrate your iPad with an Apple TV and looks at various ways of using an iPad as a TV remote. You'll also get plenty of suggestions for third-party apps and products, whether you want to read books not available in the iBookstore, stream music from the Internet to your iPad, convert your own DVD library to iPad-frien

21 CFR 890.5740 - Powered heating pad.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Powered heating pad. 890.5740 Section 890.5740...) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5740 Powered heating pad. (a) Identification. A powered heating pad is an electrical device intended for medical purposes...

Teach Yourself VISUALLY iPad

CERN Document Server

Watson, Lonzell

2010-01-01

An ideal, visual guide for the image-driven iPad. Whether your interests veer towards movies, games, books, or music—the iPad is the computing device for dazzling graphics, crisp and clear audio, and effortless portability. If ever there existed a device that demanded a reading companion for the visual learner, it's the iPad—and this resource is perfectly suited for the visual audience. Veteran VISUAL author Lonzell Watson walks you through all the features unique to the iPad and shows you how to download books, apps, music, and video content, as well as send photos and e-mails. Plus, you'll d

Generation of monoclonal antibodies against peptidylarginine deiminase 2 (PAD2) and development of a PAD2-specific enzyme-linked immunosorbent assay

DEFF Research Database (Denmark)

Damgaard, Dres; Palarasah, Yaseelan; Skjødt, Karsten

2014-01-01

The enzyme peptidylarginine deiminase 2 (PAD2) has been associated with inflammatory diseases, such as rheumatoid arthritis and neurodegenerative diseases including multiple sclerosis. To investigate the association of various diseases with extracellular PAD2, we raised monoclonal antibodies (m......Abs) against rabbit PAD2 and evaluated their cross-reactivity with human PAD2 by indirect enzyme-linked immunosorbent assay (ELISA), western blotting and immunohistological staining of inflamed synovial tissue. Moreover, we established a sandwich ELISA detecting human PAD2, based on two different monoclonal...... diseases....

EL device pad-printed on a curved surface

International Nuclear Information System (INIS)

Lee, Taik-Min; Hur, Shin; Kim, Jae-Hyun; Choi, Hyun-Cheol

2010-01-01

This paper is unique in that the electroluminescence (EL) display device is fabricated on a curved surface using the pad-printing method. The precision of the pad-printing process is explored to verify whether it can be used for micro patterning. The minimum pattern size and pattern distortion, which is caused by use of the pad, were tested and simulated. The minimal pattern was found to be 35 µm wide and 2.4 µm thick. Pattern distortion when pad-printing on a flat surface, caused by the deformation of the silicon pad, was less than 5 µm. Numerical analysis shows how to estimate pattern distortion when pad-printing on a curved surface. The proposed EL display device consists of five layers, namely a bottom electrode, dielectric layer, phosphor, transparent electrode and a bus electrode. The ink of each layer was reformulated with solvents and the pad-printing conditions were controlled. A PEN film was used first in order to realize the pad-printing process condition of each layer. Finally, the EL display device was printed onto a dish with a radius of curvature of 80 mm. The luminance was 180 cd m −2

21 CFR 880.5270 - Neonatal eye pad.

Science.gov (United States)

2010-04-01

... DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use Therapeutic Devices § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food...

Disinfecting the iPad: evaluating effective methods.

Science.gov (United States)

Howell, V; Thoppil, A; Mariyaselvam, M; Jones, R; Young, H; Sharma, S; Blunt, M; Young, P

2014-06-01

Tablet computers are increasingly used in healthcare, but they may carry nosocomial pathogens. There are few data available on how to clean an iPad effectively for use in the clinical setting. We aimed to identify the most effective method of decontaminating the Apple iPad, without causing damage, and establish the duration of any residual effect. Following contamination with a microbial broth (meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE) and Clostridium difficile), we examined efficacy of iPad disinfection in the laboratory using six different disinfectant wipes: Sani-Cloth CHG 2% (chlorhexidine 2%/alcohol 70%), Clorox, Tristel, Trigene, soap and water, and plain cloth. Following cleaning, iPads were recontaminated to examine residual activity. After 480 Sani-Cloth CHG 2% disinfecting episodes, functional and visual analysis of iPads was performed by blinded subjects. With the exception of Clostridium difficile, Sani-Cloth CHG 2% and Clorox wipes were most effective against MRSA and VRE, and they were significantly better than the Apple-recommended plain cloth (P ≤ 0.001). A substantial residual antimicrobial effect was seen for >6h after wiping the iPad with Sani-Cloth CHG 2% despite repeated recontamination and without further disinfection. The functionality or visual appearance of the iPad was not damaged by repeated use of Sani-Cloth CHG 2% wipes. Sani-Cloth CHG 2% wipes effectively disinfect the iPad against MRSA and VRE, with a residual antibacterial effect and without causing damage. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Pad B Liquid Hydrogen Storage Tank

Science.gov (United States)

Hall, Felicia

2007-01-01

Kennedy Space Center is home to two liquid hydrogen storage tanks, one at each launch pad of Launch Complex 39. The liquid hydrogen storage tank at Launch Pad B has a significantly higher boil off rate that the liquid hydrogen storage tank at Launch Pad A. This research looks at various calculations concerning the at Launch Pad B in an attempt to develop a solution to the excess boil off rate. We will look at Perlite levels inside the tank, Boil off rates, conductive heat transfer, and radiant heat transfer through the tank. As a conclusion to the research, we will model the effects of placing an external insulation to the tank in order to reduce the boil off rate and increase the economic efficiency of the liquid hydrogen storage tanks.

iPad The Missing Manual

CERN Document Server

Biersdorfer, J

2010-01-01

The iPad 2 is faster, lighter, and more versatile than its predecessor, but there's still no printed guide to using its amazing features. That's where this full-color Missing Manual comes in. Learn how to stream HD video, make video calls, manage your email, surf the Web, listen to music, play games, and maybe even do a little iWork. This is the book that should have been in the box. Build your media library. Fill your iPad with music, movies, TV shows, eBooks, photos, and more.Share with others. Stream music, HD movies, TV shows, and more, to and from your iPad.Create your own media. Use the

Video game induced knuckle pad.

Science.gov (United States)

Rushing, Mary E; Sheehan, Daniel J; Davis, Loretta S

2006-01-01

Controversy and concern surround the video game playing fascination of children. Scientific reports have explored the negative effects of video games on youth, with a growing number recognizing the actual physical implications of this activity. We offer another reason to discourage children's focus on video games: knuckle pads. A 13-year-old black boy presented with an asymptomatic, slightly hyperpigmented plaque over his right second distal interphalangeal joint. A punch biopsy specimen confirmed knuckle pad as the diagnosis, and a traumatic etiology from video game playing was suspected. Knuckle pads can be painful, cosmetically unappealing, and refractory to treatment. They can now be recognized as yet another potential adverse consequence of chronic video game playing.

Flour pads: devices to improve CHESS fat suppression.

Science.gov (United States)

Moriya, Susumu; Miki, Yukio; Miyati, Tosiaki; Kanagaki, Mitsunori; Yokobayashi, Tsuneo

2014-01-01

We compared the suppression of lingering fat signals in chemical shift selective (CHESS) images by pads filled with flour and pads filled with rice in a phantom and human subjects. First, we prepared a phantom by creating an empty space in a mass of lard and filling the space with air, rice, or flour. Then, we obtained MR images of the phantoms in the center of the magnetic field and at a position 8 cm to the left (off-center) to compare lingering fat signals. MR images of the knee were obtained in 10 healthy volunteers using CHESS after placing a polyurethane sponge pillow, rice pad, or flour pad in the popliteal space under the flexed knee. We visually assessed the number of areas with lingering fat signals and the statistical differences among the groups were assessed using Tukey's test. Similarly to rice, flour clearly decreased lingering fat signals in the phantom study. A similar effect was obtained in the off-center images. In the volunteer study, the mean number of areas with lingering fat signals was 2.5 with a sponge pillow, 0.5 with the rice pad, and 0.3 with the flour pad. Those numbers were significantly different using flour pad and rice pad compared with sponge pillow (P CHESS images.

16 CFR 1632.5 - Mattress pad test procedure.

Science.gov (United States)

2010-01-01

... 1632.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS... substrate. (b) Flame resistant mattress pads. The following additional requirements shall be applicable to mattress pads which contain a chemical fire retardant. (1) These mattress pads shall be tested in...

On the Design of Tilting-Pad Thrust Bearings

OpenAIRE

Heinrichson, Niels; Santos, Ilmar

2007-01-01

Pockets are often machined in the surfaces of tilting-pad thrust bearings to allow for hydrostatic jacking in the start-up phase. Pockets and other recesses in the surfaces of bearing pads influence the pressure distribution and thereby the position of the pivot resulting in the most advantageous pad convergence ratio. In this thesis, a theoretical approach is applied in the attempt to quantify the influence of recesses in the pad surfaces. The recesses may be relatively deep and enclosed as ...

Stopping the wave of PAD.

Science.gov (United States)

Brazziel, Tracy; Cox, Lindsie; Drury, Christa; Guerra, Maria

2011-11-01

Peripheral arterial disease (PAD) has a substantial impact on individual quality of life and is a significant financial burden to society. It is underdiagnosed, and therefore, undertreated. Early detection and treatment is essential to prevent increases in morbidity and mortality. The purpose of this article is to review evidence-based articles regarding prevalence, screening, diagnosis, and management of PAD. Copyright © 2011 Lippincott Williams & Wilkins.

TagPad

DEFF Research Database (Denmark)

Bornoe, Nis; Barkhuus, Louise

2013-01-01

The area of cyberinfrastructures has looked extensively at research within the natural sciences, however, the social sciences have been largely overlooked in terms of novel data collection and analysis systems. We developed a probe tool, TagPad, to look at the process for social science data...

Taking Your iPad 2 to the Max

CERN Document Server

Sadun, Erica; Sande, Steve

2011-01-01

iPad 2: It looks different. It acts different. It connects to the world, yet it is as personal as a well-worn book. And now it has two cameras!. Taking Your iPad 2 to the Max is written so that anyone can quickly get up to speed on Apple's latest hit. As bloggers at The Unofficial Apple Weblog (TUAW.com), the authors have the happy privilege of working with Apple products every day, and they'll guide you through all of the perks of being an iPad 2 owner. This book takes you from selecting and buying an iPad, to connecting it to the Internet, to using the incredible power of the iPad and all it

ACNE VULGARIS. EVALUATION OF A MEDICATED CLEANSING PAD.

Science.gov (United States)

ROTH, H L

1964-03-01

Using the technique of simultaneous, symmetrical paired comparisons, a medicated cleansing pad that can be easily used at work or at school as an adjunctive in the treatment of acne vulgaris was evaluated.The experimental pads were significantly beneficial in reducing skin oiliness and in clinical improvement of the acne. Response to standard acne therapy was faster when the pads were used adjunctively, although the significant results seen initially tended to even out as therapy continued. Use of the medicated pads produced no untoward side effects and were well accepted by patients.

ACNE VULGARIS—Evaluation of a Medicated Cleansing Pad

Science.gov (United States)

Roth, Harry L.

1964-01-01

Using the technique of simultaneous, symmetrical paired comparisons, a medicated cleansing pad that can be easily used at work or at school as an adjunctive in the treatment of acne vulgaris was evaluated. The experimental pads were significantly beneficial in reducing skin oiliness and in clinical improvement of the acne. Response to standard acne therapy was faster when the pads were used adjunctively, although the significant results seen initially tended to even out as therapy continued. Use of the medicated pads produced no untoward side effects and were well accepted by patients. PMID:14131397

A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.

Science.gov (United States)

Tangelder, Marco J D; Nwachuku, Chuke E; Jaff, Michael; Baumgartner, Iris; Duggal, Anil; Adams, George; Ansel, Gary; Grosso, Michael; Mercuri, Michele; Shi, Minggao; Minar, Erich; Moll, Frans L

2015-04-01

Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban. © The Author(s) 2015.

Ouders positief over iPad in het onderwijs

NARCIS (Netherlands)

Klaas Jan Huizing; Kirsten Andringa; Jildou Braaksma

2014-01-01

In 2012 is de iPad geïmplementeerd in het voorgezet middelbare onderwijs van Piter Jelles de Dyk in Leeuwarden. Sowijs volgde de implementatie van de iPad. In dit whitepaper wordt beschreven hoe ouders van leerlingen het iPad-gebruik op school ervaren. Welke voor- of nadelen zien zij in het

Comparison of postural sway depending on balance pad type.

Science.gov (United States)

Lee, DongGeon; Kim, HaNa; An, HyunJi; Jang, JiEun; Hong, SoungKyun; Jung, SunHye; Lee, Kyeongbong; Choi, Myong-Ryol; Lee, Kyung-Hee; Lee, GyuChang

2018-02-01

[Purpose] The purpose of the present study was to compare the postural sway of healthy adults standing on different types of balance pads. [Subjects and Methods] Nine healthy adults participated in this study. Postural body sway was measured while participants were standing on four different types of balance pads: Balance-pad Elite (BE), Aero-Step XL (AS), Dynair Ballkissen Senso (DBS), and Dynair Ballkissen XXL Meditation and Yoga (DBMY). A Wii Balance Board interfaced with Balancia software was used to measure postural body sway. [Results] In the sway velocity, sway path length, and sway area, no significant differences were found between baseline conditions (participants were standing on the floor with no balance pad) and the use of the BE or AS. However, significant increases in all parameters were found comparing baseline conditions to the use of either Dynair balance pad. Furthermore, the use of either Dynair balance pad significantly increased postural sway compared to both the BE and the AS. [Conclusion] These findings suggest that the DBS and DBMY balance pads may serve as superior tools for providing unstable condition for balance training than the BE and the AS balance pads.

POWER SPECTRUM DENSITY (PSD ANALYSIS OF AUTOMOTIVE PEDAL-PAD

Directory of Open Access Journals (Sweden)

AHMED RITHAUDDEEN YUSOFF

2016-04-01

Full Text Available Vibration at the pedal-pad may contribute to discomfort of foot plantar fascia during driving. This is due to transmission of vibration to the mount, chassis, pedal, and then to the foot plantar fascia. This experimental study is conducted to determine the estimation of peak value using the power spectral density of the vertical vibration input at the foot. The power spectral density value is calculated based on the frequency range between 13 Hz to 18 Hz. This experiment was conducted using 12 subjects testing on three size of pedal-pads; small, medium and large. The result shows that peak value occurs at resonance frequency of 15 Hz. The PSD values at that resonance frequency are 0.251 (m/s2 2/Hz for small pedal-pad, followed by the medium pedal-pad is at 0.387 (m/s2 2/Hz and lastly for the large pedal-pad is at 0.483 (m/s22/Hz. The resultsindicate that during driving, the foot vibration when interact with the large pedal-pad contributed higher stimulus compared with the small and medium pedal-pad. The pedal-pad size plays an important role in the pedal element designs in terms of vibration-transfer from pedal-pads on the feet, particularly to provide comfort to the driver while driving.

iPad For Seniors For Dummies

CERN Document Server

Muir, Nancy C

2010-01-01

The full-color guide to the exciting new iPad, written specifically with the needs of seniors in mind!. The iPad is the perfect device for the senior market, combining the Web, e-mail, photos, video, and book reading into an intuitive, portable device. Written by veteran Dummies author Nancy Muir, this fun and friendly guide shows you how to use the many features and capabilities of the iPad to make life easier! You'll learn how to use the multitouch screen to zoom in and out on Web pages and choose a font and size that makes reading comfortable so that you can get directions, plan vacations,

Diagnosis of heel pad injuries

DEFF Research Database (Denmark)

Matteoli, Sara

The biomechanics of in vivo heel pads has been investigated for more than 30 years, but unfortunately numerical results from the many individual investigators cannot be compared due to the different methodologies used, and the sometimes modest number of subjects investigated. The overall aim...... of the present thesis is to obtain a thorough understanding of the mechanical properties of in vivo human heel pad by studying the anatomical and physiological structure of healthy and diseased tissue, and to develop quantitative methods for diagnosing injuries. A compression device was built in order to record...... load-displacement curves from in vivo heel pads. To ensure applicability also for pathological feet, the device uses force levels lower than those needed to reproduce the physiological conditions of walking. One hundred twenty seven healthy volunteers were enrolled for compression tests and ultrasound...

iPads in Higher Education--Hype and Hope

Science.gov (United States)

Nguyen, Lemai; Barton, Siew Mee; Nguyen, Linh Thuy

2015-01-01

This paper systematically reviews current research on using iPads in the higher education sector. Since the release of iPads by Apple in 2010, this new technology has been quickly adopted everywhere, especially by the younger generation and professionals. We were motivated to find out how iPads have been adopted for use in the higher education…

Er iPad digital udeskole?

DEFF Research Database (Denmark)

Schilhab, Theresa

2014-01-01

Hvor ’konkret’ skal en oplevelse være, for at intuitionen om, at det selvoplevede styrker læringen, holder? Er brug af tablets (e.g. iPads) et ligebyrdigt alternativ til den konkrete oplevelse?......Hvor ’konkret’ skal en oplevelse være, for at intuitionen om, at det selvoplevede styrker læringen, holder? Er brug af tablets (e.g. iPads) et ligebyrdigt alternativ til den konkrete oplevelse?...

On the Design of Tilting-Pad Thrust Bearings

DEFF Research Database (Denmark)

Heinrichson, Niels

2007-01-01

Pockets are often machined in the surfaces of tilting-pad thrust bearings to allow for hydrostatic jacking in the start-up phase. Pockets and other recesses in the surfaces of bearing pads influence the pressure distribution and thereby the position of the pivot resulting in the most advantageous...... based on the Reynolds equation are used. They include the effects of variations of viscosity with temperature and the deformation of the bearing pads due to pressure and thermal gradients. The models are validated using measurements. Tilting-pad bearings of standard design are studied and the influences...... of the friction loss. Both this bearing and the bearing design with enclosed recesses in the high-pressure regions of the pads suffer from a higher sensitivity to the position of the pivot. The design of such bearing is therefore no trivial task....

New Rising Infection: Human Herpesvirus 6 Is Frequent in Myeloma Patients Undergoing Autologous Stem Cell Transplantation after Induction Therapy with Bortezomib

Directory of Open Access Journals (Sweden)

Netanel Horowitz

2012-01-01

Full Text Available Herpesvirus 6 (HHV-6 infection is a common complication during immunosuppression. Its significance for multiple myeloma (MM patients undergoing autologous stem cell transplantation (ASCT after treatment with novel agents affecting immune system remains undetermined. Data on 62 consecutive MM patients receiving bortezomib-dexamethasone (VD (; 66% or thalidomide-dexamethasone (TD (, 34% induction, together with melphalan 200 mg/m2 autograft between 01.2005 and 09.2010, were reviewed. HHV-6 reactivation was diagnosed in patients experiencing postengraftment unexplained fever (PEUF in the presence of any level of HHHV-6 DNA in blood. There were no statistically significant differences in patient characteristics between the groups, excluding dexamethasone dosage, which was significantly higher in patients receiving TD. Eight patients in TD and 18 in VD cohorts underwent viral screening for PEUF. HHV-6 reactivation was diagnosed in 10 patients of the entire series (16%, accounting for 35% of those screened; its incidence was 19.5% ( in the VD group versus 9.5% ( in the TD group. All patients recovered without sequelae. In conclusion, HHV-6 reactivation is relatively common after ASCT, accounting for at least a third of PEUF episodes. Further studies are warranted to investigate whether bortezomib has an impact on HHV-6 reactivation development.

Binocular iPad treatment for amblyopia in preschool children.

Science.gov (United States)

Birch, Eileen E; Li, Simone L; Jost, Reed M; Morale, Sarah E; De La Cruz, Angie; Stager, David; Dao, Lori; Stager, David R

2015-02-01

Recent experimental evidence supports a role for binocular visual experience in the treatment of amblyopia. The purpose of this study was to determine whether repeated binocular visual experience with dichoptic iPad games could effectively treat amblyopia in preschool children. A total of 50 consecutive amblyopic preschool children 3-6.9 years of age were assigned to play sham iPad games (first 5 children) or binocular iPad games (n = 45) for at least 4 hours per week for 4 weeks. Thirty (67%) children in the binocular iPad group and 4 (80%) in the sham iPad group were also treated with patching at a different time of day. Visual acuity and stereoacuity were assessed at baseline, at 4 weeks, and at 3 months after the cessation of game play. The sham iPad group had no significant improvement in visual acuity (t4 = 0.34, P = 0.75). In the binocular iPad group, mean visual acuity (plus or minus standard error) improved from 0.43 ± 0.03 at baseline to 0.34 ± 0.03 logMAR at 4 weeks (n = 45; paired t44 = 4.93; P iPad games for ≥8 hours (≥50% compliance) had significantly more visual acuity improvement than children who played 0-4 hours (t43 = 4.21, P = 0.0001). Repeated binocular experience, provided by dichoptic iPad game play, was more effective than sham iPad game play as a treatment for amblyopia in preschool children. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Using iPads to Your Advantage

Science.gov (United States)

Zakrzewski, Jennifer L.

2016-01-01

In this article, middle school mathematics teacher Jennifer Zakrzewski describes how she successfully incorporated iPads and Apple TV (for projection of iPad screens) into her classroom while having her students solve a problem about mangoes. As Zakrzewski began a unit on multiplying and dividing fractions, she chose to start with the Mangoes…

Resident iPad use: has it really changed the game?

Science.gov (United States)

Berkowitz, Seth J; Kung, Justin W; Eisenberg, Ronald L; Donohoe, Kevin; Tsai, Leo L; Slanetz, Priscilla J

2014-02-01

The purpose of this study was to assess residents' usage patterns and opinions of the iPad as a tool for radiology education and clinical practice at an academic medical center. All 38 radiology residents in our radiology program (postgraduate years 2 to 5) were provided with iPad 2 tablets and subscriptions to e-Anatomy and STATdx. After 6 months of device use, residents were surveyed to assess their opinions regarding the technology as a tool for education and clinical practice. A total of 36 residents (95%) completed the survey. Eighty-six percent reported daily iPad use. Radiology-specific applications, particularly e-Anatomy, were used weekly or daily by 88% of respondents. Most preferred to read journal articles on the iPad (70%), but the number of respondents preferring to read textbooks on the iPad (48.5%) compared with the traditional bound form (48.5%) was evenly divided. Residents were also divided on the clinical utility of the iPad. Most had not used the iPad to view radiologic examinations (75%). Fewer than half (47%) used their iPads during readout. Finally, only 12% had used the iPad to edit dictated reports. The iPad has generated excitement within the radiology community, particularly among resident educators, who are increasingly recognizing the unique needs of "millennial learners." This study showed that the majority of residents at the authors' institution have incorporated the iPad as an educational tool and use it as a learning aid. Incorporation of the iPad into clinical workflow has been less pronounced. Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Learning Chinese Idioms through iPads

Science.gov (United States)

Yang, Chunsheng; Xie, Ying

2013-01-01

This paper reports on an action research study using iPads during the teaching of Chinese idioms to heritage learners. A class of 12 second-year Chinese learners were engaged in a self-generated learning process focused on learning abstract and concrete idioms using iPads. Students' short-term and long-term learning was measured; feedback from a…

Development of Asbestos - Free Brake Pad Using Bagasse

Directory of Open Access Journals (Sweden)

V. S. Aigbodion

2010-03-01

Full Text Available Development of asbestos-free brake pad using bagasse was investigated with a view to replace the use of asbestos whose dust is carcinogenic. The bagasse were sieve into sieve grades of 100, 150, 250, 350 and 710µm. the sieve bagasse was used in production of brake pad in ratio of 70%bagasse-30%resin using compression moulding. The properties examined are microstructure analysis, hardness, compressive strength, density, flame resistance, water and oil absorption. The microstructure reveals uniform distribution of resin in the bagasse. The results obtained showed that the finer the sieve size the better the properties. The results obtained in this work were compared with that of commercial brake pad (asbestos based and optimum formulation laboratory brake pad Palm Kernel Shell based (PKS, the results are in close agreement. Hence bagasse can be used in production of asbestos-free brake pad.

Medical student use of the iPad in the clerkship curriculum.

Science.gov (United States)

Youm, Julie; Wiechmann, Warren

2015-12-01

There is little precedence for the implementation of a medical school iPad programme in a clinical setting. This study analysed students' use of iPad apps and perceptions of the iPad as a clinical tool in a clinical third-year medical school curriculum. All third-year medical students (n = 103) were provided iPads for use during their regular clinical rotations. Students received an orientation that included an introduction to the recommended apps selected for the study. A pre-survey (82.5% response rate) and post-survey (47.6% response rate) were administered to determine students' use of specific iPad programs, activities performed on the iPad and their perceptions. Students reported technology proficiency with the iPad and positive perceptions about its use in a clinical setting. They reported using a few key apps out of the many specialty-specific apps recommended to them. Students found efficiency through their ability to study during downtime, and through quick access to information and mobile access to electronic medical records, amongst the greatest benefits of having an iPad during their rotations. Improving Wi-Fi infrastructure and offering timely iPad orientations could decrease challenges to students' clinical iPad apps use. This study analysed students' use of iPad apps and perceptions of the iPad as a clinical too. © 2015 John Wiley & Sons Ltd.

Unilateral Cervical Polyneuropathies following Concurrent Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer

Directory of Open Access Journals (Sweden)

Alhasan Elghouche

2016-01-01

Full Text Available We report a constellation of cervical polyneuropathies in a patient treated with concurrent bortezomib, cetuximab, and cisplatin alongside intensity modulated radiotherapy for carcinoma of the tonsil with neck metastasis. The described deficits include brachial plexopathy, cervical sensory neuropathy, and oculosympathetic, recurrent laryngeal, and phrenic nerve palsies within the ipsilateral radiation field. Radiation neuropathy involving the brachial plexus is typically associated with treatment of breast or lung cancer; however, increased awareness of this entity in the context of investigational agents with potential neuropathic effects in head and neck cancer has recently emerged. With this report, we highlight radiation neuropathy in the setting of investigational therapy for head and neck cancer, particularly since these sequelae may present years after therapy and entail significant and often irreversible morbidity.

Elastic modulus of tree frog adhesive toe pads.

Science.gov (United States)

Barnes, W Jon P; Goodwyn, Pablo J Perez; Nokhbatolfoghahai, Mohsen; Gorb, Stanislav N

2011-10-01

Previous work using an atomic force microscope in nanoindenter mode indicated that the outer, 10- to 15-μm thick, keratinised layer of tree frog toe pads has a modulus of elasticity equivalent to silicone rubber (5-15 MPa) (Scholz et al. 2009), but gave no information on the physical properties of deeper structures. In this study, micro-indentation is used to measure the stiffness of whole toe pads of the tree frog, Litoria caerulea. We show here that tree frog toe pads are amongst the softest of biological structures (effective elastic modulus 4-25 kPa), and that they exhibit a gradient of stiffness, being stiffest on the outside. This stiffness gradient results from the presence of a dense network of capillaries lying beneath the pad epidermis, which probably has a shock absorbing function. Additionally, we compare the physical properties (elastic modulus, work of adhesion, pull-off force) of the toe pads of immature and adult frogs.

IT Does Not Love iPads

Science.gov (United States)

Fredette, Michelle

2013-01-01

On many campuses, iPads have taken over the hearts and minds of everyone. Everyone, that is, except the IT department. These sexy tablets might be the apple of faculty and students' eyes, but for IT directors and their staffs, working with iPads in an enterprise network environment is not the stuff of a love affair. To state the problem…

Enter the iPad (or Not?)

Science.gov (United States)

Waters, John K.

2010-01-01

Few computing devices have sparked the burning gizmo lust ignited by the iPad. Apple's latest entry into the tablet PC market didn't generate much heat when it was first unveiled in January, but by April 3, the day of the official release, feverish customers were mobbing Apple stores. The company claims to have sold 300,000 iPads by midnight on…

Updated survivals and prognostic factor analysis in myeloma treated by a staged approach use of bortezomib/thalidomide/dexamethasone in transplant eligible patients

Directory of Open Access Journals (Sweden)

Chim Chor

2010-11-01

Full Text Available Abstract Background Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM. We have reported a promising complete remission (CR rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT. Methods Herein, with an additional 13 months of follow-up, we reported the updated survivals, and examined potential prognostic factors impacting event-free (EFS and overall survival (OS. Results With a median follow-up of 30 months, the projected OS was 73% and EFS was 50.2%. Age, gender, clinical stage and DAPK methylation could not account for the differential chemosensitivity. Advanced ISS stage and DAPK methylation adversely impacted OS whereas oligoclonal reconstitution predicted superior EFS. Conclusions Our staged approach illustrated an economical use of expensive targeted agents while preserving a good CR rate and OS. The comparable survivals of chemosensitive and less chemosensitive patients suggested the staged approach might have abolished the adverse prognostic impact of suboptimal chemosensitivity. Finally, the adverse impact of DAPK methylation and favorable impact of oligoclonal reconstitution in myeloma warrants further study.

iPad use in Iowa Research Network family physician offices.

Science.gov (United States)

Daly, Jeanette M; Xu, Yinghui; Levy, Barcey T

2015-04-01

Through a cancer research infrastructure building grant, iPads were given to health care providers in family physician offices. The purpose of this study was to determine the use and application of iPads in the Iowa Research Network. A Qualtrics survey was sent to 81 iPad recipients after institutional review board approval. Fifty-nine percent responded and 85% reported they have used the iPad. The main reason for use of the iPad was browsing the World Wide Web for health care information. Open-ended comments supported use of the iPad for photographic documentation of wound and other skin lesions for insertion into the medical record and it helped improve clinic flow by making it easier to put orders in the system through the iPad. Tablet uses are variable in physician offices with provider's gathering health care information from the Internet and securing education material for patients as the frequent usages. © The Author(s) 2014.

Tests of MVD prototype pad detector with a β- source

International Nuclear Information System (INIS)

Yeol Kim, Sang; Gook Kim, Young; Su Ryu, Sang; Hwan Kang, Ju; Simon-Gillo, Jehanne; Sullivan, John P.; Heck, Hubert W. van; Xu Guanghua

1999-01-01

The MVD group has been testing two versions of silicon pad detectors. One design uses a single metal layer for readout trace routing. The second type uses two layers of metal, allowing for greatly simplified signal routing. However, because the readout traces for the pads pass over the other pads in the same column (separated by an oxide layer), the double-metal design introduces crosstalk into the system. A simple test stand using a 90 Sr β - source with scintillator triggers was made to estimate the crosstalk. The crosstalk between pads in the same column of the pad detector was 1.6-3.1%. The values measured between pads in different columns were very close to zero. The measured crosstalk was below our maximum allowed value of 7.8%

Stretchable touch-sensing skin over padding for co-robots

International Nuclear Information System (INIS)

Chen, Ying; Yu, Miao; Bruck, Hugh A; Smela, Elisabeth

2016-01-01

For robots that work collaboratively with people, often referred to as ‘co-robots’, it would be beneficial for them to be soft or padded and to have a touch-sensing ‘skin’ to enable tactile environmental awareness. However, a sensing skin over a padding material that undergoes large deformations requires ‘stretchable’ materials, which may possess time-dependent or viscoelastic mechanical responses. In this work the roles that a padding layer plays when placed under a stretchable sensing layer was investigated. A strain-sensing skin was formed by coating a thin film of compliant piezoresistive sensing paint, consisting of exfoliated graphite in latex, onto a rubber membrane, and the response of the skin was characterized. The change in resistance was linear with tensile strain. The role of the padding material was then investigated under indentation by examining three foams and two elastomers. As expected, the padding enhanced energy dissipation as shown by hysteresis in the sensor response, which is linked to its protective function; the hysteresis was comparable for the five padding materials. The padding also provided an unexpected advantage: it magnified the change in resistance compared to that obtained under free displacement in air. While hysteresis in viscoelastic materials can largely be handled with an appropriate model, inconsistency cannot be, and the two elastomers were found to have unacceptably high variability because of micro-cracks and other defects in these materials. On the other hand, foams that had few defects and regular cell sizes gave good consistency across trials and different sensor positions over the padding. Combined with their lighter weight and availability in a wide range of stiffness, we conclude that foams make a better choice for padding of co-robots. (paper)

LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.

Science.gov (United States)

Shu, Chang; Zeng, Tianmei; Gao, Shouhong; Xia, Tianyi; Huang, Lifeng; Zhang, Feng; Chen, Wansheng

2016-08-15

Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. The determination of 6 commonly used drug concentrations, including thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin, in MM patients was of great clinical interest. Herein, we reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge(®) BEH C18 column (2.5μm, 2.1 mm×50mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3mL/min. All analytes showed good correlation coefficients (r>0.996), and LLOQ of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin were 4, 2, 2, 2, 2 and 2ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The LC-MS/MS based assay described in this article may improve future clinical studies evaluating common therapeutics for MM treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Teach yourself visually the new iPad

CERN Document Server

Watson, Lonzell

2012-01-01

A new edition of a bestseller, fully updated on the latest features of the iPad! The evolution of the iPad continues to deliver amazing possibilities, which is exactly why this bestselling guide evolves right along with it! Fully updated with coverage on the latest generation of the iPad, this full-color, step-by-step guide is perfectly suited for anyone who is a visual learner and learns best by visual cues and a tactile interface. You'll learn to access and download books, apps, music, and video content as well as send photos and emails, sync with other devices and services, and confidently

Surface-modified polymeric pads for enhanced performance during chemical mechanical planarization

International Nuclear Information System (INIS)

Deshpande, S.; Dakshinamurthy, S.; Kuiry, S.C.; Vaidyanathan, R.; Obeng, Y.S.; Seal, S.

2005-01-01

The chemical mechanical planarization (CMP) process occurs at an atomic level at the slurry/wafer interface and hence slurries and polishing pads play a critical role in their successful implementation. Polyurethane is a commonly used polymer in the manufacturing of CMP pads. These pads are incompatible with some chemicals present in the CMP slurries, such as hydrogen peroxide. To overcome these problems, Psiloquest has developed new Application Specific Pads (ASP). Surface of such pads has been modified by depositing a thin film of tetraethyl orthosilicate using plasma-enhanced chemical vapor deposition (PECVD) process. In the present study, mechanical properties of such coated pads have been investigated using nanoindentation. The surface morphology and the chemistry of the ASP were studied using scanning electron microcopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy techniques. It was observed that mechanical and chemical properties of the pad top surface are a function of the PECVD coating time. Such PECVD-treated pads are found to be hydrophilic and do not require storage in aqueous media during the not-in-use period. The metal removal rate using such surface-modified polishing pads was found to increase linearly with the PECVD coating time

No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

DEFF Research Database (Denmark)

Vangsted, A. J.; Soeby, K.; Klausen, T.W.

2010-01-01

. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion...

21 CFR 884.5435 - Unscented menstrual pad.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Unscented menstrual pad. 884.5435 Section 884.5435 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Therapeutic Devices § 884.5435 Unscented menstrual pad. (a)...

Student Perceptions of Classroom Engagement and Learning using iPads

OpenAIRE

Jefferson W. Streepey; Eugenia Fernandez; Timothy T. Diemer

2013-01-01

Many colleges and universities have launched iPad initiatives in an effort to enhance student learning. Despite their rapid adoption, the extent to which iPads increase student engagement and learning is not well understood. This paper reports on a multidisciplinary assessment of student perceptions of engagement and learning using iPads. Student reactions following single and multiple classroom activities using iPads were measured via a survey asking them to rate their learning and engagemen...

Pilot Study of iPad Incorporation Into Graduate Medical Education.

Science.gov (United States)

Lobo, Mark J; Crandley, Edwin F; Rumph, Jake S; Kirk, Susan E; Dunlap, Neal E; Rahimi, Asal S; Turner, A Benton; Larner, James M; Read, Paul W

2013-03-01

Increased documentation and charting requirements are challenging for residents, given duty hour limits. Use of mobile electronic devices may help residents complete these tasks efficiently. To collect initial data on usage rates, information technology (IT) support requirements, and resident use of iPads during training. In this pilot study, we provided 12 residents/fellows from various specialties at the University of Virginia with an iPad with IT support. The system used a virtual private network with access to the institution's electronic health record. Participants were allowed to develop their own methods and systems for personalized iPad use, and after 9 months they provided data on the utility of the iPad. Feedback from the IT team also was obtained. Average iPad use was 2.1 h/d (range, 0.5-6 h/d). The average self-reported reduction in administrative work due to the iPad was 2.7 h/wk (range, 0-9 h/wk). A total of 75% (9 of 12) of the users would recommend universal adoption among residents and fellows. More than 90% (11 of 12) of users reported the iPad would improve communication for coordination of care. A total of 68% (8 of 12) of users reported that an iPad facilitated their activities as educators of medical students and junior residents. Residents cited slow data entry into the electronic health record and hospital areas lacking Wi-Fi connectivity as potential drawbacks to iPad use. The IT team reported minimal support time for device setup, maintenance, and upgrades, and limited security risks. The iPad may contribute to increased clinical efficiency, reduced hours spent on administrative tasks, and enhanced educational opportunities for residents, with minimal IT support.

Morphology and properties of periwinkle shell asbestos-free brake pad

Directory of Open Access Journals (Sweden)

D.S. Yawas

2016-01-01

Full Text Available The development of asbestos-free automotive brake pad using periwinkle shell particles as frictional filler material is presented. This was with a view to exploiting the characteristics of the periwinkle shell, which is largely deposited as a waste, in replacing asbestos which has been found to be carcinogenic. Five sets of brake pads with different sieve size (710–125 μm of periwinkle shell particles with 35% resin were produced using compressive moulding. The physical, mechanical and tribological properties of the periwinkle shell particle-based brake pads were evaluated and compared with the values for the asbestos-based brake pads. The results obtained showed that compressive strength, hardness and density of the developed brake pad samples increased with decreasing the particle size of periwinkle shell from 710 to 125 μm, while the oil soak, water soak and wear rate decreased with decreasing the particle size of periwinkle shell. The results obtained at 125 μm of periwinkle shell particles compared favourably with that of commercial brake pad. The results of this research indicate that periwinkle shell particles can be effectively used as a replacement for asbestos in brake pad manufacture.

Water data: bad TPC pads, 3.6 µs and 100 ns problems

CERN Document Server

Dydak, F; Nefedov, Y; Wotschack, J; Zhemchugov, A

2004-01-01

Out of the 3972 pads of the HARP TPC, about 9% are 'bad' and not useful for the correct reconstruction of clusters. Bad pads comprise dead pads, noisy pads, and pads with low or undefined amplification. Pads may be bad at one time, but not at another. This memo discusses the sources of information which were used to declare a pad 'bad', and gives the list of bad pads for the water data (runs 19146 to 19301). Also, the 3.6 µs and 100 ns problems of the TPC readout are discussed, including the corrective measures which have been taken.

De implementatie van de iPad in het voortgezet onderwijs

NARCIS (Netherlands)

Marjorie Louwsma; Anneke van Zwol; Klaas Jan Huizing

2012-01-01

Brengt de iPad in het onderwijs meer gebruiksgemak, snelheid en studievermogen? Sowijs deed onderzoek naar de implementatie van de iPad in het voortgezet onderwijs. Wat is de visie van leerlingen en leraren over de introductie van de iPad en wat zijn belangrijke aanbevelingen?

Modelling and simulation of a compliant tilting pad air bearing

NARCIS (Netherlands)

Duijnhouwer, F.; Nijmeijer, H.

The compliant tilting pad air bearing concept, a tilting pad bearing with the pivot of the pads placed on radial springs, is a promising aerodynamic bearing solution. Nevertheless, its non-linear dynamics make a time domain dynamic simulation model an essential tool for the design of rotor systems

cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas

DEFF Research Database (Denmark)

Manfè, Valentina; Biskup, Edyta; Willumsgaard, Ayalah

2013-01-01

Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could...... improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed c...

Pad stress tests with increasing load for the diagnosis of stress urinary incontinence.

Science.gov (United States)

Rimstad, Liv; Larsen, Elsa Skjønhaug; Schiøtz, Hjalmar A; Kulseng-Hanssen, Sigurd

2014-09-01

The aim of the study was to test the ability of pad stress tests with increasing load (supine, jumping on the floor, and jumping on a trampoline) to document stress incontinence in subjectively stress incontinent women. In this prospective study 147 subjectively stress and mixed incontinent women performed consecutively the three pad stress tests with a bladder volume of 300 ml. Nineteen women performed a second trampoline pad stress test to test repeatability of the test. Nine continent women performed a trampoline pad stress test in order to determine if subjectively continent women would leak during the test. Seventy-two women (49%) leaked during the supine, 136 (93%) leaked during the jumping, and 146 (99%) leaked during the trampoline pad stress test. The differences between pad stress tests were significant with P trampoline pad stress tests was high at 0.8. None of the nine continent women leaked during the trampoline pad stress test. The supine pad stress test has low sensitivity and is therefore often falsely negative. The jumping pad stress test is a simple test to perform and is satisfactory for everyday use. Subjectively stress incontinent women who do not leak during the jumping pad stress test may perform a trampoline pad stress test to document stress incontinence. The trampoline pad stress test is also simple to perform and detected leakage in 91% of the women who did not leak during the jumping pad stress test. © 2013 Wiley Periodicals, Inc.

Correlations for Saturation Efficiency of Evaporative Cooling Pads

Science.gov (United States)

Jain, J. K.; Hindoliya, D. A.

2014-01-01

This paper presents some experimental investigations to obtain correlations for saturation efficiency of evaporative cooling pads. Two commonly used materials namely aspen and khus fibers along with new materials namely coconut fibers and palash fibers were tested in a laboratory using suitably fabricated test setup. Simple mathematical correlations have been developed for calculating saturation efficiency of evaporating cooling pads which can be used to predict their performance at any desired mass flow rate. Performances of four different pad materials were also compared using developed correlations. An attempt was made to test two new materials (i.e. fibers of palash wood and coconut) to check their suitability as wetted media for evaporative cooling pads. It was found that Palash wood fibers offered highest saturation efficiency compared to that of other existing materials such as aspen and khus fibers at different mass flow rate of air.

Development and field performance of indy race car head impact padding.

Science.gov (United States)

Melvin, J W; Bock, H; Anderson, K; Gideon, T

2001-11-01

The close-fitting cockpit of the modern Indy car single seat race car has the potential to provide a high level of head and neck impact protection in rear and side impacts. Crash investigation has shown that a wide variety of materials have been used as the padding for these cockpits and, as a result, produced varying outcomes in crashes. Additionally, these pads have not always been positioned for optimal performance. The purpose of this study was to investigate the head impact performance of a variety of energy-absorbing padding materials under impact conditions typical of Indy car rear impacts and to identify superior materials and methods of improving their performance as race car head pads. An extensive series of tests with the helmeted Hybrid III test dummy head and neck on an impact mini-sled was conducted to explore head padding concepts. Following this, a performance specification for a simplified impact test using a rigid headform that simulates the helmeted head was developed and recommendations for performance levels of head padding based on biomechanical data on helmeted head impacts were made. In 1997, during the time that the head pad research was being performed, the Indy Racing League introduced a new chassis specification for their cars. There were a number of rear- and side-impact crashes during that season that resulted in seven severe head injuries. Examples of the head padding in those cars were included in the experimental study. The results of the head pad research were used to specify new padding materials that met the new biomechanical criteria. The placement of the head pads was also changed for better location of the padding. These changes instituted in 1998 have reduced the number of head injuries in crashes similar to or more severe than those of 1997 and have resulted in only occasional moderate head injuries (concussions) in the 1998 and 1999 seasons.

Bortezomib initiates endoplasmic reticulum stress, elicits autophagy and death in Echinococcus granulosus larval stage

Science.gov (United States)

Nicolao, María Celeste; Loos, Julia A.; Rodriguez Rodrigues, Christian; Beas, Viviana

2017-01-01

Cystic echinococcosis (CE) is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz), a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P Echinococcus cell viability, we evaluated the efficacy of Bz in combination with rapamycin and a synergistic cytotoxic effect on protoscolex viability was observed when both drugs were used together. In conclusion, our findings demonstrated that Bz induced endoplasmic reticulum stress, autophagy and subsequent death allowing to identify unstudied parasite-host pathways that could provide a new insight for control of parasitic diseases. PMID:28817601

Exploring anatomy and physiology using iPad applications.

Science.gov (United States)

Chakraborty, Tandra R; Cooperstein, Deborah F

2017-11-07

This study examined the use of iPads with anatomy applications (apps) in the laboratory sections of the largest undergraduate course at the university, Anatomy and Physiology, serving more than 300 students. The majority of these students were nursing, exercise science/physical education and biology majors. With a student survey (student opinion) and student practicum grades as metrics, this study determined whether the introduction of this novel mobile technology improved student grades and aided the students in learning the course material. The results indicated that students' grades improved with the introduction of the iPads, and 78% of the students reported that the iPads facilitated their ability to learn the course material. There was a positive association between frequency of app use and standardized mastery of the course material, as students who used the apps more frequently scored higher and indicated that they felt as though they had learned the material more comprehensively. Owning or having an iPad at home did not have a significant effect on the learning of the material. The general consensus by students was that iPad anatomy apps should be used frequently to better develop student understanding of the course material. Anat Sci Educ. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Impact response of US Army and National Football League helmet pad systems

Energy Technology Data Exchange (ETDEWEB)

Moss, W C; King, M J

2011-02-18

Lawrence Livermore National Laboratory [LLNL] was tasked to compare the impact response of NFL helmet pad systems and U.S. Army pad systems compatible with an Advanced Combat Helmet [ACH] at impact velocities up to 20 ft/s. This was a one-year study funded by the U.S. Army and JIEDDO. The Army/JIEDDO point of contact is COL R. Todd Dombroski, DO, JIEDDO Surgeon. LLNL was chosen by committee to perform the research based on prior published computational studies of the mechanical response of helmets and skulls to blast. Our collaborators include the U.S. Army Aeromedical Research Laboratory [USAARL] (a DoD laboratory responsible for impact testing helmets), Team Wendy and Oregon Aero (current and former ACH pad manufacturers), Riddell and Xenith (NFL pad manufacturers), and d3o (general purpose sports pad manufacturer). The manufacturer-supplied pad systems that were studied are shown in the figure below. The first two are the Army systems, which are bilayer foam pads with both hard and soft foam and a water-resistant airtight wrapper (Team Wendy) or a water-resistant airtight coating (Oregon Aero). The next two are NFL pad systems. The Xenith system consists of a thin foam pad and a hollow air-filled cylinder that elastically buckles under load. The Riddell system is a bilayer foam pad that is encased in an inflatable airbag with relief channels to neighboring pads in the helmet. The inflatable airbag is for comfort and provides no enhancement to impact mitigation. The d3o system consists of a rate-sensitive homogeneous dense foam. LLNL performed experiments to characterize the material properties of the individual foam materials and the response of the complete pad systems, to obtain parameters needed for the simulations. LLNL also performed X-ray CT scans of an ACH helmet shell that were used to construct a geometrically accurate computational model of the helmet. Two complementary sets of simulations were performed. The first set of simulations reproduced the

Predict optimize the friction characteristics of brake pads; Brake pad no masatsu tokusei no yosoku to saitekika

Energy Technology Data Exchange (ETDEWEB)

Saotome, H [Nissin Kogyo Co., Tokyo (Japan); Kato, T [The University of Tokyo, Tokyo (Japan)

1997-10-01

The effect of the friction and the wear properties of brake pads were experimentally studied using a test rig of scale of 1/10 of the system used in a commercial car. The experimental data were investigated by the Multiple Regression Analysis and the Neural Network, and the effects of volume % of components on the friction and the wear properties were predicted. In addition the components of brake pads are optimized by Genetic Algorithms. 8 refs., 9 figs., 4 tabs.

Computerized spiral analysis using the iPad.

Science.gov (United States)

Sisti, Jonathan A; Christophe, Brandon; Seville, Audrey Rakovich; Garton, Andrew L A; Gupta, Vivek P; Bandin, Alexander J; Yu, Qiping; Pullman, Seth L

2017-01-01

Digital analysis of writing and drawing has become a valuable research and clinical tool for the study of upper limb motor dysfunction in patients with essential tremor, Parkinson's disease, dystonia, and related disorders. We developed a validated method of computerized spiral analysis of hand-drawn Archimedean spirals that provides insight into movement dynamics beyond subjective visual assessment using a Wacom graphics tablet. While the Wacom tablet method provides robust data, more widely available mobile technology platforms exist. We introduce a novel adaptation of the Wacom-based method for the collection of hand-drawn kinematic data using an Apple iPad. This iPad-based system is stand-alone, easy-to-use, can capture drawing data with either a finger or capacitive stylus, is precise, and potentially ubiquitous. The iPad-based system acquires position and time data that is fully compatible with our original spiral analysis program. All of the important indices including degree of severity, speed, presence of tremor, tremor amplitude, tremor frequency, variability of pressure, and tightness are calculated from the digital spiral data, which the application is able to transmit. While the iPad method is limited by current touch screen technology, it does collect data with acceptable congruence compared to the current Wacom-based method while providing the advantages of accessibility and ease of use. The iPad is capable of capturing precise digital spiral data for analysis of motor dysfunction while also providing a convenient, easy-to-use modality in clinics and potentially at home. Copyright © 2016 Elsevier B.V. All rights reserved.

Fibrous scar in the infrapatellar fat pad after arthroscopy. MR imaging

International Nuclear Information System (INIS)

Tang, Guangyu; Niitsu, Mamoru; Ikeda, Kotaro; Itai, Yuji; Endo, Hideho

2000-01-01

We describe the MR appearance of fibrous scars in the infrapatellar fat pad after arthroscopy. The subjects were 96 patients who underwent arthroscope-assisted anterior cruciate ligament (ACL) reconstruction and were examined by oblique sagittal MR imaging at different follow-up intervals. Two observers evaluated the characteristics of the fibrous scars in the infrapatellar fat pad. All fibrous scars with low signal intensity were accentuated at the portal and coursed horizontally through the infrapatellar fat pad. The fibrous scar within the fat pad occurred and peaked within 6 months after arthroscopy. It then subsided gradually and had disappeared by one year later in nearly half of the patients. Identifying MR imaging characteristics of fibrous scars in the fat pad after arthroscopy may be clinically helpful to differentiate these scars from other abnormalities that involve the infrapatellar fat pad. (author)

Fibrous scar in the infrapatellar fat pad after arthroscopy. MR imaging

Energy Technology Data Exchange (ETDEWEB)

Tang, Guangyu; Niitsu, Mamoru; Ikeda, Kotaro; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Endo, Hideho

2000-02-01

We describe the MR appearance of fibrous scars in the infrapatellar fat pad after arthroscopy. The subjects were 96 patients who underwent arthroscope-assisted anterior cruciate ligament (ACL) reconstruction and were examined by oblique sagittal MR imaging at different follow-up intervals. Two observers evaluated the characteristics of the fibrous scars in the infrapatellar fat pad. All fibrous scars with low signal intensity were accentuated at the portal and coursed horizontally through the infrapatellar fat pad. The fibrous scar within the fat pad occurred and peaked within 6 months after arthroscopy. It then subsided gradually and had disappeared by one year later in nearly half of the patients. Identifying MR imaging characteristics of fibrous scars in the fat pad after arthroscopy may be clinically helpful to differentiate these scars from other abnormalities that involve the infrapatellar fat pad. (author)

Analysis of the gas-lubricated flat-sector-pad thrust bearing

Science.gov (United States)

Etsion, I.

1976-01-01

A flat sector-shaped pad geometry for a gas-lubricated thrust bearing is analyzed considering both the pitch and roll of the pad. It is shown that maximum load capacity is achieved when the pad is tilted so as to create uniform minimum film thickness along the pad trailing edge. Performance characteristics for various geometries and operating conditions of gas thrust bearings are presented in the form of design curves, and a comparison is made with the rectangular slider approximation. It is found that this approximation is unsafe for practical design, since it always overestimates load capacity.

Perceptions and use of iPad technology by pharmacy practice faculty members.

Science.gov (United States)

DiVall, Margarita V; Zgarrick, David P

2014-04-17

To explore the potential of tablet technology to address the specific workload challenges of pharmacy practice faculty members and to evaluate tablet usage after a department-wide iPad initiative. After conducting a needs assessment to determine pharmacy faculty attitudes towards tablet technology and to identify potential usage scenarios, all faculty members in a department of pharmacy practice received an iPad. After iPad distribution, training sessions and virtual tutorials were provided. An anonymous survey was administered to evaluate the pilot. The needs assessment survey revealed positive attitudes towards iPad technology, identified use scenarios, and led to a department-wide iPad pilot program. Most faculty members used iPads for connectivity with students (86%), paper/project annotation (68%), assessment (57%), and demonstration of tools used in practice (36%). For teaching, 61% of faculty members used iPads in seminars/laboratories, 57% used iPads in the experiential setting, and 43% used iPads in the classroom. Use of iPads for patient-care activities varied and depended on site support for mobile technology. The 23 faculty members with external practice sites used iPads to a greater extent and had more positive attitudes towards this technology compared with campus-based faculty members. Integration of tablet technology into the pharmacy education setting resulted in faculty-reported increased productivity and decreased paper waste. It also allowed faculty members to experiment with new teaching strategies in the classroom and experiential setting. Administrators at institutions exploring the use of tablet technology should allocate resources based on faculty needs and usage patterns.

Launch Pad in a Box

Science.gov (United States)

Mantovani, James; Tamasy, Gabor; Mueller, Rob; Townsend, Van; Sampson, Jeff; Lane, Mike

2016-01-01

NASA Kennedy Space Center (KSC) is developing a new deployable launch system capability to support a small class of launch vehicles for NASA and commercial space companies to test and launch their vehicles. The deployable launch pad concept was first demonstrated on a smaller scale at KSC in 2012 in support of NASA Johnson Space Center's Morpheus Lander Project. The main objective of the Morpheus Project was to test a prototype planetary lander as a vertical takeoff and landing test-bed for advanced spacecraft technologies using a hazard field that KSC had constructed at the Shuttle Landing Facility (SLF). A steel pad for launch or landing was constructed using a modular design that allowed it to be reconfigurable and expandable. A steel flame trench was designed as an optional module that could be easily inserted in place of any modular steel plate component. The concept of a transportable modular launch and landing pad may also be applicable to planetary surfaces where the effects of rocket exhaust plume on surface regolith is problematic for hardware on the surface that may either be damaged by direct impact of high speed dust particles, or impaired by the accumulation of dust (e.g., solar array panels and thermal radiators). During the Morpheus free flight campaign in 2013-14, KSC performed two studies related to rocket plume effects. One study compared four different thermal ablatives that were applied to the interior of a steel flame trench that KSC had designed and built. The second study monitored the erosion of a concrete landing pad following each landing of the Morpheus vehicle on the same pad located in the hazard field. All surfaces of a portable flame trench that could be directly exposed to hot gas during launch of the Morpheus vehicle were coated with four types of ablatives. All ablative products had been tested by NASA KSC and/or the manufacturer. The ablative thicknesses were measured periodically following the twelve Morpheus free flight tests

Diagnostic accuracy of heel pad palpation - A phantom study

DEFF Research Database (Denmark)

Torp-Pedersen, Søren; Matteoli, Sara; Wilhjelm, Jens E.

2008-01-01

Falanga torture involves repetitive blunt trauma to the soles of the feet and typically leaves few detectable changes. Reduced elasticity in the heel pads has been reported as characteristic sequelae and palpatory testing of heel pad elasticity is therefore part of medicolegal assessment of alleged...... torture victims. The goal was to test the accuracy of two experienced investigators in determining whether a heel pad model was soft, medium or hard. The skin-to-bone distance in the models varied within the human range....

Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States.

Science.gov (United States)

Jakubowiak, Andrzej J; Houisse, Ivan; Májer, István; Benedict, Ágnes; Campioni, Marco; Panjabi, Sumeet; Ailawadhi, Sikander

2017-12-01

We assessed the economic value of carfilzomib 56 mg/m 2 and dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients. Utilities were sourced from the literature and mapped from patient-reported quality of life in ENDEAVOR to estimate quality-adjusted life-years (QALYs) from life-years (LYs). The model predicted an average gain of 1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior treatment; $99,263/QALY in those not transplanted, and discount in bortezomib price. Kd56 is cost-effective for patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial data in the model may limit generalizability; however, SEER registry data mitigates this challenge. Kd56 provides additional value in key subgroups, and remains cost-effective after steep comparator discounts.

Pad use and patient reported bother from urinary leakage after radical prostatectomy.

Science.gov (United States)

Wallerstedt, Anna; Carlsson, Stefan; Nilsson, Andreas E; Johansson, Eva; Nyberg, Tommy; Steineck, Gunnar; Wiklund, N Peter

2012-01-01

To better understand clinically significant definitions of urinary incontinence we investigated the relationship between urinary leakage and patient reported bother from urinary leakage. A consecutive series of 1,411 men who underwent radical prostatectomy at Karolinska University Hospital, Stockholm, Sweden, from 2002 to 2006 were invited to complete a study specific questionnaire with questions on pad status, urinary leakage and bother from urinary leakage. Questionnaires were received from 1,179 men with a followup of greater than 1 year (median 2.2). Results showed that even a small amount of urinary leakage resulted in a high risk of urinary bother. Of 775 survivors 46 (6%) reporting 0 pads indicated moderate or much bother compared to 38 of 123 (31%) who reported using a security pad. When comparing the 2 groups, the risk of bother from urinary leakage was more than 5 times higher in the safety pad vs the 0 pad group (RR 5.2, 95% CI 3.5-7.7). As the number of pads increased, we noted a higher bother risk. Cross-tabulation of pad use and urinary leakage revealed wide variation in pad requirements despite the same answer to urinary leakage questions. If the definition of continence is based on pad use, for example safety pads, a certain number of men who report moderate or much bother from urinary leakage will be defined as continent. Our results also show that for each stated rate of urinary leakage men prove to have a major variation in the pad requirement. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Validation of an iPad test of letter contrast sensitivity.

Science.gov (United States)

Kollbaum, Pete S; Jansen, Meredith E; Kollbaum, Elli J; Bullimore, Mark A

2014-03-01

An iPad-based letter contrast sensitivity test was developed (ridgevue.com) consisting of two letters on each page of an iBook. The contrast decreases from 80% (logCS = 0.1) to 0.5% (logCS = 2.3) by 0.1 log units per page. The test was compared to the Pelli-Robson Test and the Freiburg Acuity and Contrast Test. Twenty normally sighted subjects and 20 low-vision subjects were tested monocularly at 1 m using each test wearing their habitual correction. After a 5-minute break, subjects were retested with each test in reverse order. Two different letter charts were used for both the Pelli-Robson and iPad tests, and the order of testing was varied systematically. For the Freiburg test, the target was a variable contrast Landolt C presented at eight possible orientations and used a 30-trial Best PEST procedure. Repeatability and agreement were assessed by determining the 95% limits of agreement (LoA) ± 1.96 SD of the differences between administrations or tests. All three tests showed good repeatability in terms of the 95% LoA: iPad = ± 0.19, Pelli-Robson = ± 0.19, and Freiburg = ± 0.15. The iPad test showed good agreement with the Freiburg test with similar mean (± SD) logCS (iPad = 1.98 ± 0.11, Freiburg = 1.96 ± 0.06) and with narrow 95% LoA (± 0.24), but the Pelli-Robson test gave significantly lower values (1.65 ± 0.04). Low-vision subjects had slightly poorer repeatability (iPad = ± 0.24, Pelli-Robson = ± 0.23, Freiburg = ± 0.21). Agreement between the iPad and Freiburg tests was good (iPad = 1.45 ± 0.40, Freiburg = 1.54 ± 0.37), but the Pelli-Robson test gave significantly lower values (1.30 ± 0.30). The iPad test showed similar repeatability and may be a rapid and convenient alternative to some existing measures. The Pelli-Robson test gave lower values than the other tests.

Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution.

Science.gov (United States)

Tang, Min; Zhao, Rui; van de Velde, Helgi; Tross, Jennifer G; Mitsiades, Constantine; Viselli, Suzanne; Neuwirth, Rachel; Esseltine, Dixie-Lee; Anderson, Kenneth; Ghobrial, Irene M; San Miguel, Jesús F; Richardson, Paul G; Tomasson, Michael H; Michor, Franziska

2016-08-15

Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Effect of comfort pads and incubator design on neonatal radiography

Energy Technology Data Exchange (ETDEWEB)

Jiang, Xia; Baad, Michael; Reiser, Ingrid; Feinstein, Kate A.; Lu, Zhengfeng [University of Chicago Medicine, Department of Radiology, Chicago, IL (United States)

2016-01-15

There has been increasing interest in patient dose reduction in neonatal intensive care units. Removing comfort pads for radiography has been identified as a potential means to decrease patient dose. To assess the effect of comfort pads and support trays on detector entrance exposure (DEE) and image quality for neonatal radiography, and its implication for patient dose. Comfort pads and support trays from three incubator and warmer systems were examined. The attenuation of the primary beam by these structures was measured using a narrow beam geometry. Their effect on DEE and image quality was then assessed using typical neonatal chest radiography techniques with three configurations: (1) both the comfort pad and support included in the beam, (2) only the support tray included and (3) both the comfort pad and support tray removed. Comfort pads and support trays were found to attenuate the primary beam by 6-15%. Eliminating these structures from the X-ray beam's path was found to increase the detector entrance exposure by 28-36% and increase contrast-to-noise ratio by more than 21%, suggesting room for patient dose reduction when the same image quality is maintained. Comfort pads and tray support devices can have a considerable effect on DEE and image quality, with large variations among different incubator designs. Positioning the image detector directly underneath neonatal patients for radiography is a potential means for patient dose reduction. However, such benefit should be weighed against the risks of moving the patient. (orig.)

Effect of comfort pads and incubator design on neonatal radiography

International Nuclear Information System (INIS)

Jiang, Xia; Baad, Michael; Reiser, Ingrid; Feinstein, Kate A.; Lu, Zhengfeng

2016-01-01

There has been increasing interest in patient dose reduction in neonatal intensive care units. Removing comfort pads for radiography has been identified as a potential means to decrease patient dose. To assess the effect of comfort pads and support trays on detector entrance exposure (DEE) and image quality for neonatal radiography, and its implication for patient dose. Comfort pads and support trays from three incubator and warmer systems were examined. The attenuation of the primary beam by these structures was measured using a narrow beam geometry. Their effect on DEE and image quality was then assessed using typical neonatal chest radiography techniques with three configurations: (1) both the comfort pad and support included in the beam, (2) only the support tray included and (3) both the comfort pad and support tray removed. Comfort pads and support trays were found to attenuate the primary beam by 6-15%. Eliminating these structures from the X-ray beam's path was found to increase the detector entrance exposure by 28-36% and increase contrast-to-noise ratio by more than 21%, suggesting room for patient dose reduction when the same image quality is maintained. Comfort pads and tray support devices can have a considerable effect on DEE and image quality, with large variations among different incubator designs. Positioning the image detector directly underneath neonatal patients for radiography is a potential means for patient dose reduction. However, such benefit should be weighed against the risks of moving the patient. (orig.)

Proof Pad: A New Development Environment for ACL2

Directory of Open Access Journals (Sweden)

Caleb Eggensperger

2013-04-01

Full Text Available Most software development projects rely on Integrated Development Environments (IDEs based on the desktop paradigm, with an interactive, mouse-driven user interface. The standard installation of ACL2, on the other hand, is designed to work closely with Emacs. ACL2 experts, on the whole, like this mode of operation, but students and other new programmers who have learned to program with desktop IDEs often react negatively to the process of adapting to an unfamiliar form of interaction. This paper discusses Proof Pad, a new IDE for ACL2. Proof Pad is not the only attempt to provide ACL2 IDEs catering to students and beginning programmers. The ACL2 Sedan and DrACuLa systems arose from similar motivations. Proof Pad builds on the work of those systems, while also taking into account the unique workflow of the ACL2 theorem proving system. The design of Proof Pad incorporated user feedback from the outset, and that process continued through all stages of development. Feedback took the form of direct observation of users interacting with the IDE as well as questionnaires completed by users of Proof Pad and other ACL2 IDEs. The result is a streamlined interface and fast, responsive system that supports using ACL2 as a programming language and a theorem proving system. Proof Pad also provides a property-based testing environment with random data generation and automated interpretation of properties as ACL2 theorem definitions.

Modeling of Tilting-Pad Journal Bearings with Transfer Functions

Directory of Open Access Journals (Sweden)

J. A. Vázquez

2001-01-01

Full Text Available Tilting-pad journal bearings are widely used to promote stability in modern rotating machinery. However, the dynamics associated with pad motion alters this stabilizing capacity depending on the operating speed of the machine and the bearing geometric parameters, particularly the bearing preload. In modeling the dynamics of the entire rotor-bearing system, the rotor is augmented with a model of the bearings. This model may explicitly include the pad degrees of freedom or may implicitly include them by using dynamic matrix reduction methods. The dynamic reduction models may be represented as a set of polynomials in the eigenvalues of the system used to determine stability. All tilting-pad bearings can then be represented by a fixed size matrix with polynomial elements interacting with the rotor. This paper presents a procedure to calculate the coefficients of polynomials for implicit bearing models. The order of the polynomials changes to reflect the number of pads in the bearings. This results in a very compact and computationally efficient method for fully including the dynamics of tilting-pad bearings or other multiple degrees of freedom components that interact with rotors. The fixed size of the dynamic reduction matrices permits the method to be easily incorporated into rotor dynamic stability codes. A recursive algorithm is developed and presented for calculating the coefficients of the polynomials. The method is applied to stability calculations for a model of a typical industrial compressor.

Parametric studies on floating pad journal bearing for high speed cryogenic turboexpanders

Science.gov (United States)

Jain, A.; Jadhav, M. M.; Karimulla, S.; Chakravarty, A.

2017-12-01

Most modern medium and large capacity helium liquefaction/refrigeration plants employ high speed cryogenic turboexpanders in their refrigeration/liquefaction cycles as active cooling devices. The operating speed of these turboexpanders is in the range of 3000-5000 Hz and hence specialized types of bearings are required. Floating pad journal bearing, which is a special type of tilting pad journal bearing, where mechanical pivots are absent and pads are fully suspended in gas, can be a good solution for stable operation of these high speed compact rotors. The pads are separated from shaft as well as from housing by fluid film between them, and both these sides of pad are interconnected by a network of feed holes. The work presented in this article aims to characterize floating pad journal bearings through parametric studies. The steady state performance characteristics of the bearing are represented by load capacity, stiffness coefficients and heat generation rate of the bearing. The geometrical parameters such as bearing clearances, preload of pads, etc. are varied and performance characteristics of the floating pad journal bearing are studied and presented. The dependence of stiffness coefficients on rotational speed of shaft is also analyzed.

An alternative to conventional babbitt metal-lined generator pads

Energy Technology Data Exchange (ETDEWEB)

Puuska, H. [Imatra Hydroelectric Power Plant (Finland)

1996-08-01

The generator refurbishment of the Imatra Hydroelectric Power Plant Unit 1 in Finland is described. The generator work called for installation of a new cooling system for the generator thrust bearing. The considerations leading to the decision to replace the conventional babbitt metal-lined pads with elastic metal-plastic coated thrust bearing pads and the installation of the new pads are outlined in the article. Results of the trial run are summarized; the end temperature of the unit was more than 20C lower than for units equipped with conventional babbitted bearings.

Exploring the use of iPads in Danish schools

DEFF Research Database (Denmark)

Khalid, Md. Saifuddin; Jurisic, Olivera; Kristensen, Henrik Stein

2014-01-01

Mobile devices, especially the integration and adoption of iPads in school classrooms, is gaining emphasis across the research and development forums of academic, policy, organizational, political, and public spheres. In April 2012, the Danish government announced that they would allocate DKK 500...... of integrating and adopting desktop computers and other educational technologies. However, there are some unique advantages that iPad and other mobile devices can enable through apps, readiness, etc. Policies and strategies should be adopted to combine training and maintenance along with ensuring access to iPads....

Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

Directory of Open Access Journals (Sweden)

Balk JM

2015-08-01

Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

Nonlinear Dynamics Analysis of Tilting Pad Journal Bearing-Rotor System

Directory of Open Access Journals (Sweden)

Jiayang Ying

2011-01-01

Full Text Available The nonlinear dynamics theory is increasingly applied in the dynamics analysis of tilting pad journal bearing-rotor system. However, extensive work on system dynamics done previously neglects the influence caused by the moment of inertia of the pad. In this paper, a comparison is made between the responses of the rotor in the bearings with and without pad inertia effect. Taking the Jeffcott rotor system as an example, the characteristics of bearing-rotor system, such as bifurcation diagram, cycle response, frequency spectrum, phase trajectories, and Poincaré maps, were attained within a certain rotation rate range. The pivotal oil-film force of tilting pad journal bearing was calculated by database method. The results directly demonstrate that considering the influence of the pad moment of inertia, system dynamics characteristics are found more complicated when rotor-bearing system works around natural frequency and system bifurcation is observed forward when rotor-bearing system works on high-speed range.

Dryout power of a CANFLEX bundle string with raised bearing pads

International Nuclear Information System (INIS)

Leung, L.K.H.; Dimmick, G.R.; Bullock, D.E.; Inch, W.W.R.; Jun, J.S.; Suk, H.C.

2001-01-01

Dryout power data have been obtained with CANFLEX bundle strings equipped with raised bearing pads (1.7 mm and 1.8 mm height as compared to 1.4 mm in the current Mk-IV design) at Stern Laboratories. The experiment covered a wide range of steam-water flow conditions in three flow tubes simulating uncrept, and 3.3% and 5.1% crept profiles. The dryout power follows consistent parametric trends: it increases with increasing mass-flow rate, and decreases with increasing pressure, inlet-fluid temperature and channel creep. Local and boiling-length-average (BLA) critical-heat-flux (CHF) values were evaluated from the dryout-power measurements. The dryout power and BLA CHF values of the high bearing-pad bundles are higher than those of the low bearing-pad bundles at the same channel inlet flow conditions. On average, the dryout powers for bundles with 1.7 mm and 1.8 mm bearing pads are about 8% and 10%, respectively, higher than those for the bundle with 1.4 mm bearing pads. Compared to the 37-element bundle, an enhancement in dryout power is shown with CANFLEX bundles for all bearing-pad heights, at flow conditions of interest for reactor licensing. The average dryout power enhancement varies from 4% for the CANFLEX bundle with 1.4 mm bearing pads in the uncrept channel to 27% for the CANFLEX bundle with 1.8 mm bearing pads in the 5.1% crept channel. (author)

Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

Directory of Open Access Journals (Sweden)

Carole D Mitnick

Full Text Available A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7 drugs. Cure or completion was achieved in 66.1% (442 of patients; death occurred in 20.8% (139. Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89, compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93.The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

Effect of conditioner load on the polishing pad surface during chemical mechanical planarization process

Energy Technology Data Exchange (ETDEWEB)

Shin, Cheol Min; Qin, Hong Yi; Hong, Seok Jun; Jeon, Sang Hyuk; Kulkarni, Atul; Kim, Tae Sun [Sungkyunkwan University, Suwon (Korea, Republic of)

2016-12-15

During the Chemical mechanical planarization (CMP), the pad conditioning process can affect the pad surface characteristics. Among many CMP process parameters, the improper applied load on the conditioner arm may have adverse effects on the polyurethane pad. In this work, we evaluated the pad surface properties under the various conditioner arm applied during pad conditioning process. The conditioning pads were evaluated for surface topography, surface roughness parameters such as Rt and Rvk and Material removal rate (MRR) and within-wafer non-uniformity after wafer polishing. We observed that, the pad asperities were collapsed in the direction of conditioner rotation and blocks the pad pores applied conditioner load. The Rvk value and MRR were founded to be in relation with 4 > 1 > 7 kgF conditioner load. Hence, this study shows that, 4 kgF applied load by conditioner is most suitable for the pad conditioning during CMP.

21 CFR 890.3790 - Cane, crutch, and walker tips and pads.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cane, crutch, and walker tips and pads. 890.3790 Section 890.3790 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES..., crutch, and walker tips and pads. (a) Identification. Cane, crutch, and walker tips and pads are rubber...

A combination drift chamber/pad chamber for very high readout rates

International Nuclear Information System (INIS)

Spiegel, L.; Cataldi, G.; Elia, V.; Mazur, P.; Murphy, C.T.; Smith, R.P.; Yang, W.; Alexopoulos, T.; Durandet, C.; Erwin, A.; Jennings, J.; Antoniazzi, L.; Introzzi, G.; Lanza, A.; Liguori, G.; Torre, P.; Arenton, M.; Conetti, S.; Cox, B.; Dukes, E.; Golovatyuk, V.; Hanlet, P.; McManus, A.; Nelson, K.; Recagni, M.; Segal, J.; Sun, J.; Ballagh, C.; Bingham, H.; Kaeding, T.; Lys, J.; Misawa, S.; Blankman, A.; Borodin, S.; Kononenko, W.; Newcomer, M.; Selove, W.; Trojak, T.; VanBerg, R.; Zhang, S.N.; Block, M.; Corti, G.; LeCompte, T.; Rosen, J.; Yao, T.; Boden, A.; Cline, D.; Ramachandran, S.; Rhoades, J.; Tokar, S.; Budagov, J.; Tsyganov, E.; Cao, Z.L.; He, M.; Wang, C.; Wei, C.; Zhang, N.; Chen, T.Y.; Yao, N.; Clark, K.; Jenkins, M.; Cooper, M.; Creti, P.; Gorini, E.; Grancagnolo, F.; Panareo, M.; Fortney, L.; Kowald, W.; Haire, M.; Judd, D.; Turnbull, L.; Wagoner, D.; Lau, K.; Mo, G.; Trischuk, J.

1991-11-01

Six medium-sized (∼1 x 2 m 2 ) drift chambers with pad and stripe readout have been constructed for and are presently operating in Fermi National Accelerator Laboratory experiment E-771. Each chamber module actually represents a pair of identical planes: two sets of anode wires, two sets of stripes, and two sets of pads. The wire planes are read out separately and represent X measurements in the coordinate system of the experiment. The twin stripe and pad planes are internally paired within the chamber modules; stripe signals represent Y measurements and pad signals combination X and Y measurements. Signals which develop on the stripes and pads are mirror (but inverted) images of what is seen on the wires. In addition to being used in the off-line pattern recognition, pad signals are also used as inputs to an on-line high transverse momentum (pt) trigger processor. While the techniques involved in the design and construction of the chambers are not novel, they may be of interest to experiments contemplating very large area, high rate chambers for future spectrometers

A combination drift chamber/pad chamber for very high readout rates

Energy Technology Data Exchange (ETDEWEB)

Spiegel, L.; Cataldi, G.; Elia, V.; Mazur, P.; Murphy, C.T.; Smith, R.P.; Yang, W. (Fermi National Accelerator Lab., Batavia, IL (United States)); Alexopoulos, T.; Durandet, C.; Erwin, A.; Jennings, J. (Wisconsin Univ., Madison, WI (United States)); Antoniazzi, L.; Introzzi, G.; Lanza, A.; Liguori, G.; Torre, P. (Pavia Univ. (Italy) Istituto Nazionale di Fisica Nucleare, Rome (Italy)); Arenton, M.; Conetti, S.

1991-11-01

Six medium-sized ({approx}1 {times} 2 m{sup 2}) drift chambers with pad and stripe readout have been constructed for and are presently operating in Fermi National Accelerator Laboratory experiment E-771. Each chamber module actually represents a pair of identical planes: two sets of anode wires, two sets of stripes, and two sets of pads. The wire planes are read out separately and represent X measurements in the coordinate system of the experiment. The twin stripe and pad planes are internally paired within the chamber modules; stripe signals represent Y measurements and pad signals combination X and Y measurements. Signals which develop on the stripes and pads are mirror (but inverted) images of what is seen on the wires. In addition to being used in the off-line pattern recognition, pad signals are also used as inputs to an on-line high transverse momentum (pt) trigger processor. While the techniques involved in the design and construction of the chambers are not novel, they may be of interest to experiments contemplating very large area, high rate chambers for future spectrometers.

Neurosurgical simulation by interactive computer graphics on iPad.

Science.gov (United States)

Maruyama, Keisuke; Kin, Taichi; Saito, Toki; Suematsu, Shinya; Gomyo, Miho; Noguchi, Akio; Nagane, Motoo; Shiokawa, Yoshiaki

2014-11-01

Presurgical simulation before complicated neurosurgery is a state-of-the-art technique, and its usefulness has recently become well known. However, simulation requires complex image processing, which hinders its widespread application. We explored handling the results of interactive computer graphics on the iPad tablet, which can easily be controlled anywhere. Data from preneurosurgical simulations from 12 patients (4 men, 8 women) who underwent complex brain surgery were loaded onto an iPad. First, DICOM data were loaded using Amira visualization software to create interactive computer graphics, and ParaView, another free visualization software package, was used to convert the results of the simulation to be loaded using the free iPad software KiwiViewer. The interactive computer graphics created prior to neurosurgery were successfully displayed and smoothly controlled on the iPad in all patients. The number of elements ranged from 3 to 13 (mean 7). The mean original data size was 233 MB, which was reduced to 10.4 MB (4.4% of original size) after image processing by ParaView. This was increased to 46.6 MB (19.9%) after decompression in KiwiViewer. Controlling the magnification, transfer, rotation, and selection of translucence in 10 levels of each element were smoothly and easily performed using one or two fingers. The requisite skill to smoothly control the iPad software was acquired within 1.8 trials on average in 12 medical students and 6 neurosurgical residents. Using an iPad to handle the result of preneurosurgical simulation was extremely useful because it could easily be handled anywhere.

iPads in Inclusive Classrooms: Ecologies of Learning

Science.gov (United States)

Meyer, Bente

2013-01-01

This paper builds on data from a project where iPads were used in a lower secondary school in Denmark to support school development and inclusive learning environments. The paper explores how iPads enter into and work as part of an ecology of learning in five classes in lower secondary school. The paper argues that we should disengage approaches…

iPad Use in Seventh Grade Math: Parent and Student Perceptions

Science.gov (United States)

Corbett, Robin

2015-01-01

The purpose of this qualitative research study was to compare student and parental perceptions of mobile technology use, specifically iPads, in seventh grade math classrooms and at home. How students and parents perceive the use of iPads within the seventh grade math classroom and how students and parents perceive the influence of iPad use at home…

Barriers to the Integration and Adoption of iPads in Schools

DEFF Research Database (Denmark)

Khalid, Md. Saifuddin; Kilic, Gökce; Christoffersen, Jeanette

2015-01-01

iPad, with its Apple platform and interoperability-dependent material conditions, bring complex barriers in its adoption and integration in secondary education system as a learning tool. In the schools’ context, it is an emerging educational technology for its affordances supporting collaborative...... learning. This systematic literature review on the barriers to the integration of iPad in primary and secondary schools is based on 13 peer-reviewed and full-text articles. The paper discusses what are the challenges in using iPad as a learning tool in primary and secondary educational settings....... The identified barriers are discussed in three broad categories or stages of innovation process in an educational context: basic challenges with the tool, barriers to the integration of the iPad in a school setting, and barriers in the use of the iPad....

Control and sensor techniques for PAD servo motor drive

DEFF Research Database (Denmark)

Zsurzsan, Tiberiu-Gabriel; Zhang, Zhe; Andersen, Michael A. E.

2015-01-01

The Piezoelectric Actuator Drive (PAD) is a new type of electrical motor that employs piezoelectric multilayer actuators coupled with a form-fitted micro-mechanical gearing to generate rotary motion. The PAD is precise, having a positioning error of less than 2 arc-seconds. Its typical output...

Simulating pad-electrodes with high-definition arrays in transcranial electric stimulation

Science.gov (United States)

Kempe, René; Huang, Yu; Parra, Lucas C.

2014-04-01

Objective. Research studies on transcranial electric stimulation, including direct current, often use a computational model to provide guidance on the placing of sponge-electrode pads. However, the expertise and computational resources needed for finite element modeling (FEM) make modeling impractical in a clinical setting. Our objective is to make the exploration of different electrode configurations accessible to practitioners. We provide an efficient tool to estimate current distributions for arbitrary pad configurations while obviating the need for complex simulation software. Approach. To efficiently estimate current distributions for arbitrary pad configurations we propose to simulate pads with an array of high-definition (HD) electrodes and use an efficient linear superposition to then quickly evaluate different electrode configurations. Main results. Numerical results on ten different pad configurations on a normal individual show that electric field intensity simulated with the sampled array deviates from the solutions with pads by only 5% and the locations of peak magnitude fields have a 94% overlap when using a dense array of 336 electrodes. Significance. Computationally intensive FEM modeling of the HD array needs to be performed only once, perhaps on a set of standard heads that can be made available to multiple users. The present results confirm that by using these models one can now quickly and accurately explore and select pad-electrode montages to match a particular clinical need.

Structural response testing of thermal barrier load-bearing ceramic pads

International Nuclear Information System (INIS)

Black, W.E.; Luci, R.K.; Pickering, J.L.; Oland, G.B.

1983-01-01

A load bearing insulating structure for use in a HTGR was investigated. The structure was composed of dense ceramic materials in the form of circular pads arranged in a stack. Specifically, the test program was structured to investigate the isolation effectiveness of interface materials placed between the ceramic pads to reduce the effectiveness of mechanically induced loads. The tests were conducted at room temperature using tapered loading platens on single ceramic pads. Seventeen alumina specimens, representing two types of material and two thicknesses, were tested. Three interface material thicknesses were introduced using silica cloth and graphite foil. Pre and post test nondestructive examinations were conducted in an effort to identify potential damage-inducing anomalies in the ceramic pads. A total of 62 tests was conducted with all specimens eventually loaded to failure. (orig./HP)

Pad A treatability study long-range project plan

International Nuclear Information System (INIS)

Mousseau, J.D.

1991-06-01

This plan addresses the work to be accomplished by the Pad A Treatability Study Project. The purpose of this project is to investigate potential treatment and separation technologies, identify the best technologies, and to demonstrate by both lab- and pilot-scale demonstration, the most applicable remedial technologies for treating plutonium-contaminated salts at the Pad A site located at the Subsurface Disposal Area (SDA) at the Radioactive Waste Management Complex (RWMC) a the Idaho National Engineering Laboratory (INEL). The conduct of this project will be supported by other DOE laboratories, universities, and private industries, who will provide support for near-term demonstrations of treatment and separation technologies. The purpose of this long-range planning document is to present the detailed plan for the implementation of the Pad A Treatability Study Project

Pad-weighing test performed with standardized bladder volume

DEFF Research Database (Denmark)

Lose, G; Rosenkilde, P; Gammelgaard, J

1988-01-01

The result of the one-hour pad-weighing test proposed by the International Continence Society has been demonstrated to depend on the urine load during the test. To increase reproducibility of the pad-weighing test by minimizing the influence of variation in urine load the test was done with a sta...... to +/- 24 g between two tests. It is concluded that this setup (i.e., standardized bladder volume) of the one-hour pad-weighing test allows for a more reliable assessment of urinary incontinence for quantitative purposes....... with a standardized bladder volume (50% of the cystometric bladder capacity). Twenty-five female patients with stress or mixed incontinence underwent two separate tests. Test-retest results were highly correlated (r = 0.97, p less than 0.001). Nonetheless, analysis of test-retest differences revealed a variation up...

Accurate micro Hall effect measurements on scribe line pads

DEFF Research Database (Denmark)

Østerberg, Frederik Westergaard; Petersen, Dirch Hjorth; Wang, Fei

2009-01-01

Hall mobility and sheet carrier density are important parameters to monitor in advanced semiconductor production. If micro Hall effect measurements are done on small pads in scribe lines, these parameters may be measured without using valuable test wafers. We report how Hall mobility can...... be extracted from micro four-point measurements performed on a rectangular pad. The dimension of the investigated pad is 400 × 430 ¿m2, and the probe pitches range from 20 ¿m to 50 ¿m. The Monte Carlo method is used to find the optimal way to perform the Hall measurement and extract Hall mobility most...

Assessing the iPad as a tool for low-vision rehabilitation.

Science.gov (United States)

Mednick, Zale; Jaidka, Atul; Nesdole, Robert; Bona, Mark

2017-02-01

It has been demonstrated consistently that patients with poor vision have a reduced quality of life and functional status and higher rates of psychologic distress. This study aims to assess whether the iPad has potential as a visual aid in patients with low vision. Qualitative study with key-informant interviews. Patients who identified as having impaired vision were recruited from a low vision ophthalmology clinic. Patients participated in a 4-session iPad training course. The goal of the course was to teach patients with low vision how to operate an iPad, with a particular emphasis on how to optimize iPad settings and accessibility features in response to some of the challenges faced by patients with low vision. Three interviews were conducted with each participant: before the course, immediately after the course, and 3 months after the course. The purpose of the interviews was to gain an understanding of their experience with low vision and to assess if and how the iPad had influenced this experience. A grounded theory qualitative approach was used for analysis. Six patients took part in the study and were divided into 2 separate courses to minimize course size. Participants had favorable views regarding the course. Five of the 6 participants were using the iPad on a daily basis 3 months after the course. Thematic analysis revealed that use of the iPad led to both a heightened sense of independence and improved social connectivity. It is theorized that use of the iPad as a low-vision aid may enhance a patient's sense of self-worth. With proper training, the iPad has the potential to be a valuable tool for low-vision patients. Its features help patients to gain independence and to stay connected within their social circles. Further research with a larger patient population and quantifiable endpoints should focus on these themes. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Pad for holding a load against a surface by suction

International Nuclear Information System (INIS)

Farmer, R.C.; Goldsmith, H.A.; Proudlove, M.J.

1981-01-01

This invention concerns suction pads for supporting loads. Specifically, the suction pad is part of a pair of pads located at the ends of a bridge forming a vehicle for transporting instruments for the non-destructive testing of a large vessel intended to contain a fuel assembly for a nuclear reactor immersed in a liquid metal coolant. For example, the vehicle is of the type described in the French patent application filed this day under the heading 'Vehicle for transporting instruments for testing against a wall' [fr

Estimating the Economic Impact of Adding Panobinostat to a U.S. Formulary for Relapsed and/or Refractory Multiple Myeloma: A Budget Impact and Cost-Benefit Model.

Science.gov (United States)

Bloudek, Lisa; Roy, Anuja; Kish, Jonathan K; Siegel, David S; Jagannath, Sundar; Globe, Denise; Orloski, Laurie; Kuriakose, Emil T

2016-08-01

Multiple myeloma is an incurable B-cell malignancy with a natural history that involves alternating periods of remission and subsequent relapse. For relapsed and/or refractory multiple myeloma (RRMM), the typical patient currently receives more lines of therapy than has been feasible in the past, translating into longer progression-free survival (PFS). Consequently, cost issues have become more prominent because patients may be offered newer and more expensive therapies during a more prolonged overall treatment course. To estimate the economic impact of adding panobinostat to a U.S. health plan formulary as a treatment option with bortezomib and dexamethasone for patients with RRMM previously treated with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), using a budget impact and cost-benefit model. Total costs of commonly used salvage therapy regimens were combined with market share data and population prevalence estimates of RRMM to yield the total cost of treatment, from the perspective of a U.S. third-party payer (commercial or Medicare) with a time horizon of 1 year. Comparator treatment regimens included bortezomib-dexamethasone, lenalidomide-dexamethasone, lenalidomide-bortezomib-dexamethasone, carfilzomib monotherapy, carfilzomib-lenalidomide-dexamethasone, and pomalidomide-dexamethasone. Costs (2015 U.S. dollars) included drug costs for oral oncology agents, medical and administration costs for injectable oncology agents, costs of adverse event (AE) prophylaxis and monitoring, and costs of grade 3/4 AEs. In a hypothetical health plan with 1 million members, the annual number of RRMM patients with previous PI and IMiD treatments was estimated at 16 and 118 for a commercial and Medicare plan, respectively. Introduction of panobinostat as part of the panobinostat-bortezomib-dexamethasone regimen was not expected to result in a substantial budget impact to either commercial or Medicare plans, with an incremental cost money. Funding for this study

Ultrasound appearance of knuckle pads

Energy Technology Data Exchange (ETDEWEB)

Lopez-Ben, R. [Univ. of Alabama, Birmingham (United States). Dept. of Diagnostic Radiology; Dehghanpisheh, K.; Chatham, W.W.; Alarcon, G.S. [Univ. of Alabama, Birmingham (United States). Dept. of Medicine; Lee, D.H.; Oakes, J. [Univ. of Alabama, Birmingham (United States). Dept. of Surgery

2006-11-15

We describe the ultrasound appearance of knuckle pads. Retrospective analysis of imaging in a series of five patients initially referred for evaluation of periarticular soft-tissue swelling of the hands involving the dorsum of the PIP and MP joints. Two patients had associated Dupuytren's contractures. Ultrasound and radiographs of the hands in all patients were reviewed and correlated with clinical history and physical exams. Radiographs in four patients demonstrated dorsal soft-tissue thickening. Ultrasound exams showed increased dorsal subcutaneous thickening, with either diffuse or focal hypoechoic areas corresponding to the areas of soft-tissue fullness identified on physical exam. No erosions or synovial proliferation were identified either by radiographs or ultrasound of the underlying joints. Knuckle pads can sometimes be difficult to distinguish from synovitis on physical examination. Musculoskeletal ultrasound can quickly identify these superficial lesions and exclude underlying synovial proliferation.

Rice pads. Devices to improve the effect of fat suppression of CHESS images

International Nuclear Information System (INIS)

Moriya, Susumu; Yokobayashi, Tsuneo; Miki, Yukio

2013-01-01

The chemical shift selective (CHESS) method is often used for fat suppression in magnetic resonance imaging. CHESS has several advantages, including versatility, quick imaging, and applicability to contrast examinations. One disadvantage of CHESS is the lingering fat signal generated as a result of nonuniformity of the static magnetic field. To overcome this drawback, some researchers have used pads made with polished rice (rice pads), a simple method in which rice pads are placed outside the area to be imaged. We describe ways to improve CHESS images, characteristics of the rice pad, its application to imaging, and methods of placing the pad. (author)

Identification of markers that functionally define a quiescent multiple myeloma cell sub-population surviving bortezomib treatment

International Nuclear Information System (INIS)

Adomako, Alfred; Calvo, Veronica; Biran, Noa; Osman, Keren; Chari, Ajai; Paton, James C; Paton, Adrienne W; Moore, Kateri; Schewe, Denis M; Aguirre-Ghiso, Julio A

2015-01-01

The mechanisms allowing residual multiple myeloma (MM) cells to persist after bortezomib (Bz) treatment remain unclear. We hypothesized that studying the biology of bortezomib-surviving cells may reveal markers to identify these cells and survival signals to target and kill residual MM cells. We used H2B-GFP label retention, biochemical tools and in vitro and in vivo experiments to characterize growth arrest and the unfolded protein responses in quiescent Bz-surviving cells. We also tested the effect of a demethylating agent, 5-Azacytidine, on Bz-induced quiescence and whether inhibiting the chaperone GRP78/BiP (henceforth GRP78) with a specific toxin induced apoptosis in Bz-surviving cells. Finally, we used MM patient samples to test whether GRP78 levels might associate with disease progression. Statistical analysis employed t-test and Mann-Whitney tests at a 95% confidence. We report that Bz-surviving MM cells in vitro and in vivo enter quiescence characterized by p21 CIP1 upregulation. Bz-surviving MM cells also downregulated CDK6, Ki67 and P-Rb. H2B-GFP label retention showed that Bz-surviving MM cells are either slow-cycling or deeply quiescent. The Bz-induced quiescence was stabilized by low dose (500nM) of 5-azacytidine (Aza) pre-treatment, which also potentiated the initial Bz-induced apoptosis. We also found that expression of GRP78, an unfolded protein response (UPR) survival factor, persisted in MM quiescent cells. Importantly, GRP78 downregulation using a specific SubAB bacterial toxin killed Bz-surviving MM cells. Finally, quantification of Grp78 high /CD138+ MM cells from patients suggested that high levels correlated with progressive disease. We conclude that Bz-surviving MM cells display a GRP78 HIGH /p21 HIGH /CDK6 LOW /P-Rb LOW profile, and these markers may identify quiescent MM cells capable of fueling recurrences. We further conclude that Aza + Bz treatment of MM may represent a novel strategy to delay recurrences by enhancing Bz

Structural response testing of thermal barrier load bearing ceramic pads

International Nuclear Information System (INIS)

Pickering, J.L.; Black, W.E.; Luci, R.K.; Oland, C.B.

1983-01-01

A load-bearing insulating structure for use in a high-temperature gas-cooled reactor (HTGR) was investigated. The structure was composed of dense ceramic materials in the form of circular pads arranged in a stack. Specifically, the test program was structured to investigate the isolation effectiveness of interface materials placed between the ceramic pads to reduce the effectiveness of mechanically induced loads. The tests were conducted at room temperature using tapered loading platens on single ceramic pads. Seventeen alumina specimens, representing two types of material and two thicknesses, were tested. Three interface material thicknesses were introduced using silica cloth and graphite foil. Pre- and post-test nondestructive examinations were conducted in an effort to identify potential damage-inducing anomalies in the ceramic pads. A total of 62 tests was conducted with all specimens eventually loaded to failure

Biomechanical Comparison of Shorts With Different Pads

Science.gov (United States)

Marcolin, Giuseppe; Petrone, Nicola; Reggiani, Carlo; Panizzolo, Fausto A.; Paoli, Antonio

2015-01-01

Abstract An intensive use of the bicycle may increase the risk of erectile dysfunction and the compression of the perineal area has been showed to be a major mechanism leading to sexual alterations compromising the quality of life. Manufacturers claim that pads contribute to increase cyclists perineal protection ensuring a high level of comfort. To investigate the influence of various cycling pads with regard to perineal protection and level of comfort. Nine club road cyclists rode 20 min on a drum simulator, located at the Nutrition and Exercise Physiology Laboratory, at a constant speed and gear ratio wearing the shorts with 3 cycling pads of different design and thickness: basic (BAS), intermediate (INT), and endurance (END). Kinematics and pressure data were recorded at min 5, 15, and 20 of the test using a motion capture system and a pressure sensor mat. The variables of interest were: 3-dimensional pelvis excursions, peak pressure, mean pressure, and vertical force. The comfort level was assessed with a ranking order based on the subjects’ perception after the 20-min trials and measuring the vertical ground reaction force under the anterior wheel as well as the length of the center of pressure (COP) trajectory on the saddle. Results showed that the vertical force and the average value of mean pressure on the saddle significantly decreased during the 20-min period of testing for BAS and END. Mean peak pressure on the corresponding perineal cyclist area significantly increased only for BAS during the 20-min period. Interestingly objective comfort indexes measured did not match cyclists subjective comfort evaluation. The lower capacity of BAS to reduce the peak pressure on the corresponding perineal area after 20 min of testing, together with its positive comfort evaluation, suggest that a balance between protection and perceived comfort should be taken into account in the choice of the pad. Hence, the quantitative approach of objective comfort indexes

Bit-padding information guided channel hopping

KAUST Repository

Yang, Yuli

2011-02-01

In the context of multiple-input multiple-output (MIMO) communications, we propose a bit-padding information guided channel hopping (BP-IGCH) scheme which breaks the limitation that the number of transmit antennas has to be a power of two based on the IGCH concept. The proposed scheme prescribes different bit-lengths to be mapped onto the indices of the transmit antennas and then uses padding technique to avoid error propagation. Numerical results and comparisons, on both the capacity and the bit error rate performances, are provided and show the advantage of the proposed scheme. The BP-IGCH scheme not only offers lower complexity to realize the design flexibility, but also achieves better performance. © 2011 IEEE.

Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad.

Science.gov (United States)

Adamson, Trinka W; Kendall, Lon V; Goss, Sherri; Grayson, Kevin; Touma, Chadi; Palme, Rupert; Chen, Jane Q; Borowsky, Alexander D

2010-09-01

The purpose of this study was to determine the level of pain elicited by mammary fat pad removal surgery and the effects of postoperative analgesics on recovery. Female FVB mice were anesthetized, and mammary fat pad removal was performed. After surgery, mice received carprofen, buprenorphine, a combination of carprofen and buprenorphine, or saline treatment. Additional mice received anesthesia but no surgery or treatment. Food and water intake, body weight, wheel running activity, and a visual assessment score were recorded daily for 4 d after surgery and compared with presurgical findings. Corticosterone metabolites in fecal samples were analyzed at 12 and 24 h postsurgically and compared with baseline values. All surgical groups had significantly decreased food intake at 24 h, with a return to baseline by 48 h. The combination treatment resulted in a significantly decreased water intake and body weight at 24 h. All surgical groups had significantly decreased wheel running activity at 24 h only. The visual assessment scores indicated mild pain for all surgical groups, with the buprenorphine treated mice showing the highest pain index scores, as compared with nonsurgical controls. Fecal corticosterone metabolite levels did not differ significantly between any of the groups or across time. The parameters used in this study did not indicate that administration of these analgesic regimens improved recovery as compared with that of saline-treated mice. Care should be taken when using visual assessment scores to evaluate pain in mice, given that analgesics may have side effects that inadvertently elevate the score.

Development of radiation shielding materials and NBC pads for infantry combat vehicle and tank

International Nuclear Information System (INIS)

Pal, R.S.; Gautam, O.P.; Katiyar, Mohit; Tripathi, D.N.; Singh, R.K.

2008-01-01

Tanks have special lining materials inside, providing a certain degree of radiation protection for operation in nuclear scenario's. At present these special lining materials in the form of sheets are imported and are fitted into armoured vehicles. Three types of polymer compositions; PE(M)SE, PEC-ISE and PEC-IISE were formulated based on polymer matrix, specific fillers and anti-ageing additives. Prototype NBC pads based on polymer composition PEC-ISE was finalized for moulding of NBC pads for use in ICVs and composition PE(M)SE was finalized for T-90 tanks. The physico-mechanical properties for NBC pads have been evaluated. Radiography of test samples was conducted to ensure homogeneity of specific fillers in the polymer matrix. Radiation shielding factors against nuclear radiation sources ( 60 Co, I37 Cs and 252 Cf) were evaluated at DL Jodhpur and found to be better than imported Russian Pads designed for ICVs and T-90 Tanks. Drawings for twelve types of NBC pads for ICVs and one hundred eighteen types of pads for T-90 tank were generated with the help of design tool, Auto Desk Inventor-II and metallic moulds for moulding of NBC pads were fabricated. Prototype NBC pads were moulded through compression moulding process. Radiation protection factors of prototype NBC pads, after fitment in ICVs, were also evaluated against neutron and gamma (primary and secondary) radiation sources. Prototype NBC pads for ICVs have shown 20% improvement in overall protection level and NBC pads for T-90 tanks have been developed as per design requirements. Manufacturing facility for NBC shielding pads have been established in association with industries. (author)

iPads: Improving Numeracy Learning in the Early Years

Science.gov (United States)

Spencer, Peta

2013-01-01

The concept of mobile technologies is now an emergency theme in educational research, yet the playing of these edutainment applications and their impact on early childhood learning needs to be fully explored. This study highlights current research and explores how iPads improve student learning. It also examines how the introduction of iPads,…

iPad Use and Student Engagement in the Classroom

Science.gov (United States)

Mango, Oraib

2015-01-01

iPads and handheld digital devices have been securing their place in educational institutions surrounded by debates between advocates and skeptics. In light of not enough evidence supporting the use of iPads in education, this study examined the ways that college students in two foreign language classrooms perceived the influence of the use of…

Tilting-Pad Guide Bearing in Large Hydro-unit

Directory of Open Access Journals (Sweden)

Li-Feng Ma

2000-01-01

Full Text Available A new numerical method is proposed for predicting the nonlinearity of tilting-pad guide bearing oilfilm force in the rotor-bearing system in a large hydro-unit. Nonlinear displacement and velocity of the journal center, as well as nonlinear tilting angles and angular velocities of the pads in non-stationary Reynolds equation are taken into account. This method is also suited for other small rotor-bearing system. As an example, the response due to a momentarily created unbalance is Calculated. The nonlinear motion patterns of the pad and journal whirling orbit are obtained. Finally, the nonlinear orbit is compared to the linear one that could be calculated from linear stiffness and damping coefficients. It is shown that there are important differences between those two orbits and that the nonlinear simulation is more accurate.

ImagePAD, a novel counting application for the Apple iPad, used to quantify axons in the mouse optic nerve.

Science.gov (United States)

Templeton, Justin P; Struebing, Felix L; Lemmon, Andrew; Geisert, Eldon E

2014-11-01

The present article introduces a new and easy to use counting application for the Apple iPad. The application "ImagePAD" takes advantage of the advanced user interface features offered by the Apple iOS platform, simplifying the rather tedious task of quantifying features in anatomical studies. For example, the image under analysis can be easily panned and zoomed using iOS-supported multi-touch gestures without losing the spatial context of the counting task, which is extremely important for ensuring count accuracy. This application allows one to quantify up to 5 different types of objects in a single field and output the data in a tab-delimited format for subsequent analysis. We describe two examples of the use of the application: quantifying axons in the optic nerve of the C57BL/6J mouse and determining the percentage of cells labeled with NeuN or ChAT in the retinal ganglion cell layer. For the optic nerve, contiguous images at 60× magnification were taken and transferred onto an Apple iPad. Axons were counted by tapping on the touch-sensitive screen using ImagePAD. Nine optic nerves were sampled and the number of axons in the nerves ranged from 38,872 axons to 50,196 axons with an average of 44,846 axons per nerve (SD = 3980 axons). Copyright © 2014 Elsevier Ltd. All rights reserved.

iPhone and iPad apps for absolute beginners

CERN Document Server

Lewis, Rory

2013-01-01

So how do you build an application for the iPhone and iPad? Don't you need to spend years learning complicated programming languages? What about Objective-C and Cocoa touch? The answer is that you don't need to know any of those things! Anybody can start building simple apps for the iPhone and iPad, and this book will show you how. This update of an Apress bestseller walks you through creating your first app, using plain English and practical examples using the iOS 6 software development platform and more. It cuts through the fog of jargon and misinformation that surrounds iPhone and iPad app

iBooks and ePeriodicals on the iPad

CERN Document Server

Biersdorfer, J

2010-01-01

This Mini Missing Manual takes you down the virtual rows of Apple's iBookstore, to help you find, buy, and download books and subscribe to magazine and newspapers on your iPad. You'll learn now to navigate your books and periodicals and sync them back to iTunes to swap them on and off your iPad to free up storage space. In addition, you'll find out where to get free books in the iBookstore, and where you can shop for iPad-compatible books, both free and for-pay, outside of Apple's domain. Finally, you'll learn the fine art of eBook navigation, including how to change a book's font and font

Variation in training regimens in professional showjumping yards

NARCIS (Netherlands)

Lönnell, A C; Bröjer, J; Nostell, K; Hernlund, E; Roepstorff, L; Tranquille, C A; Murray, R C; Oomen, A; van Weeren, René; Bitschnau, C; Montavon, S; Weishaupt, M A; Egenvall, A

2014-01-01

REASONS FOR PERFORMING STUDY: Training regimens of showjumping horses under field conditions are largely undocumented. OBJECTIVES: The aims of this study were to quantify and compare training regimens used in professional-level showjumping yards, with respect to time exercised and type of activity.

Pad-mode-induced instantaneous mode instability for simple models of brake systems

Science.gov (United States)

Oberst, S.; Lai, J. C. S.

2015-10-01

Automotive disc brake squeal is fugitive, transient and remains difficult to predict. In particular, instantaneous mode squeal observed experimentally does not seem to be associated with mode coupling and its mechanism is not clear. The effects of contact pressures, friction coefficients as well as material properties (pressure and temperature dependency and anisotropy) for brake squeal propensity have not been systematically explored. By analysing a finite element model of an isotropic pad sliding on a plate similar to that of a previously reported experimental study, pad modes have been identified and found to be stable using conventional complex eigenvalue analysis. However, by subjecting the model to contact pressure harmonic excitation for a range of pressures and friction coefficients, a forced response analysis reveals that the dissipated energy for pad modes is negative and becomes more negative with increasing contact pressures and friction coefficients, indicating the potential for instabilities. The frequency of the pad mode in the sliding direction is within the range of squeal frequencies observed experimentally. Nonlinear time series analysis of the vibration velocity also confirms the evolution of instabilities induced by pad modes as the friction coefficient increases. By extending this analysis to a more realistic but simple brake model in the form of a pad-on-disc system, in-plane pad-modes, which a complex eigenvalue analysis predicts to be stable, have also been identified by negative dissipated energy for both isotropic and anisotropic pad material properties. The influence of contact pressures on potential instabilities has been found to be more dominant than changes in material properties owing to changes in pressure or temperature. Results here suggest that instantaneous mode squeal is likely caused by in-plane pad-mode instabilities.

Metacarpophalangeal joint synovial pad fibrotic proliferation in 63 horses

International Nuclear Information System (INIS)

Dabareiner, R.M.; White, N.A.; Sullins, K.E.

1996-01-01

Medical records, radiographs, and sonograms of 63 horses with metacarpophalangeal joint synovial pad proliferation were examined retrospectively. AR horses had lameness, joint effusion, or both signs associated with one or both metacarpophalangeal joints. Bony remodeling and concavity of the distodorsal aspect of the third metacarpal bone (Mc3) just proximal to the metacarpal condyles was identified by radiography in 71 joints (93%); 24 joints (32%) had radiographic evidence of a chip fracture located at the proximal dorsal aspect of the proximal phalanx. Fifty-four joints (71%) were examined by ultrasound. The mean +- SD sagittal thickness of the synovial pad was 11.3 +- 2.8 mm. Seventy-nine percent of the horses had single joint involvement with equal distribution between the right and left forelimbs. Sixty-eight joints in 55 horses were treated by arthroscopic surgery. Sixty joints (88%) had debridement of chondral or osteochondral fragmentation from the dorsal surface of Mc3 beneath the synovial pad and 30 joints (44%) had a bone chip fracture removed from the medial or lateral proximal dorsal eminence of the proximal phalanx. Complete or partial excision of both medial and lateral synovial pads was completed in 42 joints. Only the medial synovial pad was excised or trimmed in 21 joints, and 5 joints had only the lateral pad removed. Eight joints in eight horses were treated by stall rest, administration of intra-articular medication and systemic nonsteroidal anti-inflammatory drugs. Follow-up information was obtained for 50 horses treated surgically and for eight horses treated medically. Forty-three (86%) that had surgery returned to racing; 34 (68%) raced at an equivalent or better level than before surgery. Three (38%) of the medically treated horses returned to racing; only one horse raced better than the preinjury level. Horses that returned to racing at a similar or equal level of performance were significantly younger in age than horses returning at a

Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

DEFF Research Database (Denmark)

Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

2011-01-01

the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1–2.4)). Furthermore, among INF-α treated patients, gene–gene interaction studies on IL1B C-3737T and NFКB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

A novel nonlinear nano-scale wear law for metallic brake pads.

Science.gov (United States)

Patil, Sandeep P; Chilakamarri, Sri Harsha; Markert, Bernd

2018-05-03

In the present work, molecular dynamics simulations were carried out to investigate the temperature distribution as well as the fundamental friction characteristics such as the coefficient of friction and wear in a disc-pad braking system. A wide range of constant velocity loadings was applied on metallic brake pads made of aluminium, copper and iron with different rotating speeds of a diamond-like carbon brake disc. The average temperature of Newtonian atoms and the coefficient of friction of the brake pad were investigated. The resulting relationship of the average temperature with the speed of the disc as well as the applied loading velocity can be described by power laws. The quantitative description of the volume lost from the brake pads was investigated, and it was found that the volume lost increases linearly with the sliding distance. Our results show that Archard's linear wear law is not applicable to a wide range of normal loads, e.g., in cases of low normal load where the wear rate was increased considerably and in cases of high load where there was a possibility of severe wear. In this work, a new formula for the brake pad wear in a disc brake assembly is proposed, which displays a power law relationship between the lost volume of the metallic brake pads per unit sliding distance and the applied normal load with an exponent of 0.62 ± 0.02. This work provides new insights into the fundamental understanding of the wear mechanism at the nano-scale leading to a new bottom-up wear law for metallic brake pads.

IntelligentPad for exchanging and reusing nuclear reaction data information as shared resources

International Nuclear Information System (INIS)

Chiba, Masaki

1996-01-01

As an application of the IntelligentPad system, the NRDF database system is redesigned and developed. In the system, every component of the user interface is represented by reactive media objects called Pad. The exploitation of the IntelligentPad architecture in developing the system enhances the usability and reusability of the tools developed. Several pads specially designed for the NRDF database system are shown together with the examples of how to use them. (author)

Syringolin A selectively labels the 20 S proteasome in murine EL4 and wild-type and bortezomib-adapted leukaemic cell lines.

Science.gov (United States)

Clerc, Jérôme; Florea, Bogdan I; Kraus, Marianne; Groll, Michael; Huber, Robert; Bachmann, André S; Dudler, Robert; Driessen, Christoph; Overkleeft, Herman S; Kaiser, Markus

2009-11-02

The natural product syringolin A (SylA) is a potent proteasome inhibitor with promising anticancer activities. To further investigate its potential as a lead structure, selectivity profiling with cell lysates was performed. At therapeutic concentrations, a rhodamine-tagged SylA derivative selectively bound to the 20 S proteasome active sites without detectable off-target labelling. Additional profiling with lysates of wild-type and bortezomib-adapted leukaemic cell lines demonstrated the retention of this proteasome target and subsite selectivity as well as potency even in clinically relevant cell lines. Our studies, therefore, propose that further development of SylA might indeed result in an improved small molecule for the treatment of leukaemia.

Randomized controlled study of a novel triple nitazoxanide (NTZ)-containing therapeutic regimen versus the traditional regimen for eradication of Helicobacter pylori infection.

Science.gov (United States)

Shehata, Mona Ah; Talaat, Raghda; Soliman, Samah; Elmesseri, Huda; Soliman, Shaimaa; Abd-Elsalam, Sherief

2017-10-01

Helicobacter pylori infection has become more and more resistant to conventional first-line treatment regimens. So, there is a considerable interest in evaluating new antibiotic combinations and regimens. Nitazoxanide is an anti-infective drug with demonstrated activity against protozoa and anaerobic bacteria including H. pylori. This work is designed to evaluate the efficacy and safety of a unique triple nitazoxanide-containing regimen as a treatment regimen in Egyptian patients with H. pylori infection. Two hundred and 24 patients with upper gastrointestinal tract (GIT) dyspeptic symptoms in whom H. pylori -induced GIT disease was confirmed were included in the study. They have been randomized to receive either nitazoxanide 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40 mg twice daily for 14 days or metronidazole 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40  mg twice daily for 14 days. Laboratory evaluation for H. pylori antigen within the stool was performed 6 weeks after cessation of H. pylori treatment regimens to assess the response. The response to treatment was significantly higher in group 1 of nitazoxanide treatment regimen than group 2 of traditional treatment regimen. One hundred and six cases (94.6%) of 112 patients who completed the study in group 1 showed complete cure, while only 63 cases (60.6%) of 104 patients who completed the study in group 2 showed the same response according to per-protocol (PP) analysis (Ppylori. (ClinicalTrials.gov Identifier: NCT02422706). © 2017 John Wiley & Sons Ltd.

Chemical mechanical planarization of amorphous Ge2Sb2Te5 with a soft pad

International Nuclear Information System (INIS)

He Aodong; Liu Bo; Song Zhitang; Lü Yegang; Li Juntao; Liu Weili; Feng Songlin; Wu Guanping

2013-01-01

Chemical mechanical planarization (CMP) of amorphous Ge 2 Sb 2 Te 5 (a-GST) is investigated using two typical soft pads (politex REG and AT) in acidic slurry. After CMP, it is found that the removal rate (RR) of a-GST increases with an increase of runs number for both pads. However, it achieves the higher RR and better surface quality of a-GST for an AT pad. The in-situ sheet resistance (R s ) measure shows the higher R s of a-GST polishing can be gained after CMP using both pads and the high R s is beneficial to lower the reset current for the PCM cells. In order to find the root cause of the different RR of a-GST polishing with different pads, the surface morphology and characteristics of both new and used pads are analyzed, it shows that the AT pad has smaller porosity size and more pore counts than that of the REG pad, and thus the AT pad can transport more fresh slurry to the reaction interface between the pad and a-GST, which results in the high RR of a-GST due to enhanced chemical reaction. (semiconductor technology)

Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

International Nuclear Information System (INIS)

Yuan Jiankui; Wang, Jian Z.; Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

2008-01-01

Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The α/β ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible α/β ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens

Fast micro Hall effect measurements on small pads

DEFF Research Database (Denmark)

Østerberg, Frederik Westergaard; Petersen, Dirch Hjorth; Nielsen, Peter F.

2011-01-01

Sheet resistance, carrier mobility, and sheet carrier density are important parameters in semiconductor production, and it is therefore important to be able to rapidly and accurately measure these parameters even on small samples or pads. The interpretation of four-point probe measurements on small...... pads is non-trivial. In this paper we discuss how conformal mapping can be used to evaluate theoretically expected measurement values on small pads. Theoretical values calculated from analytical mappings of simple geometries are compared to the values found from the numerical conformal mapping...... of a square onto the infinite half-plane, where well-established solutions are known. Hall effect measurements are performed to show, experimentally, that it is possible to measure Hall mobility in less than one minute on squares as small as 7070 lm2 with a deviation of 66.5% on a 1r level from accurate...

Exposure-rate calibration using large-area calibration pads

International Nuclear Information System (INIS)

Novak, E.F.

1988-09-01

The US Department of Energy (DOE) Office of Remedial Action and Waste Technology established the Technical Measurements Center (TMC) at the DOE Grand Junction Projects Office (GJPO) in Grand Junction, Colorado, to standardize, calibrate, and compare measurements made in support of DOE remedial action programs. A set of large-area, radioelement-enriched concrete pads was constructed by the DOE in 1978 at the Walker Field Airport in Grand Junction for use as calibration standards for airborne gamma-ray spectrometer systems. The use of these pads was investigated by the TMC as potential calibration standards for portable scintillometers employed in measuring gamma-ray exposure rates at Uranium Mill Tailings Remedial Action (UMTRA) project sites. Data acquired on the pads using a pressurized ionization chamber (PIC) and three scintillometers are presented as an illustration of an instrumental calibration. Conclusions and recommended calibration procedures are discussed, based on the results of these data

Internal strain estimation for quantification of human heel pad elastic modulus: A phantom study

DEFF Research Database (Denmark)

Holst, Karen; Liebgott, Hervé; Wilhjelm, Jens E.

2013-01-01

Shock absorption is the most important function of the human heel pad. However, changes in heel pad elasticity, as seen in e.g. long-distance runners, diabetes patients, and victims of Falanga torture are affecting this function, often in a painful manner. Assessment of heel pad elasticity...... is usually based on one or a few strain measurements obtained by an external load-deformation system. The aim of this study was to develop a technique for quantitative measurements of heel pad elastic modulus based on several internal strain measures from within the heel pad by use of ultrasound images. Nine...... heel phantoms were manufactured featuring a combination of three heel pad stiffnesses and three heel pad thicknesses to model the normal human variation. Each phantom was tested in an indentation system comprising a 7MHz linear array ultrasound transducer, working as the indentor, and a connected load...

iPad in the Enterprise Developing and Deploying Business Applications

CERN Document Server

Clevenger, Nathan

2011-01-01

Discover how to plan, design, develop, and deploy iPad apps for the enterprise Having taken the enterprise by storm, iPads are now in the hands of workers in virtually every level of companies in almost every industry. But using iPad apps in the enterprise is more complex than simply clicking an icon from the App Store. It presents unique challenges around software development, system integration, information security, application deployment, and device management. That's where this book comes in. iPhone Life Enterprise Editor and veteran mobile consultant Nathan Clevenger presents a guide for

Mechanical behaviour of the heel pad: experimental and numerical approach

DEFF Research Database (Denmark)

Matteoli, Sara; Fontanella, C. G.; Virga, A.

The aim of the present work was to investigate the stress relaxation phenomena of the heel pad region under different loading conditions. A 31-year-old healthy female was enrolled in this study and her left foot underwent both MRI and experimental compression tests. Experimental results were...... compared with those obtained from finite element analysis performed on numerical 3D subject-specific heel pad model built on the basis of MRI. The calcaneal fat pad tissue was described with a visco-hyperelastic model, while a fiber-reinforced hyperelastic model was formulated for the skin. The reliability...

Arachnids secrete a fluid over their adhesive pads.

Directory of Open Access Journals (Sweden)

Anne M Peattie

Full Text Available BACKGROUND: Many arachnids possess adhesive pads on their feet that help them climb smooth surfaces and capture prey. Spider and gecko adhesives have converged on a branched, hairy structure, which theoretically allows them to adhere solely by dry (solid-solid intermolecular interactions. Indeed, the consensus in the literature is that spiders and their smooth-padded relatives, the solifugids, adhere without the aid of a secretion. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the adhesive contact zone of living spiders, solifugids and mites using interference reflection microscopy, which allows the detection of thin liquid films. Like insects, all the arachnids we studied left behind hydrophobic fluid footprints on glass (mean refractive index: 1.48-1.50; contact angle: 3.7-11.2°. Fluid was not always secreted continuously, suggesting that pads can function in both wet and dry modes. We measured the attachment forces of single adhesive setae from tarantulas (Grammostola rosea by attaching them to a bending beam with a known spring constant and filming the resulting deflection. Individual spider setae showed a lower static friction at rest (26%±2.8 SE of the peak friction than single gecko setae (Thecadactylus rapicauda; 96%±1.7 SE. This may be explained by the fact that spider setae continued to release fluid after isolation from the animal, lubricating the contact zone. SIGNIFICANCE: This finding implies that tarsal secretions occur within all major groups of terrestrial arthropods with adhesive pads. The presence of liquid in an adhesive contact zone has important consequences for attachment performance, improving adhesion to rough surfaces and introducing rate-dependent effects. Our results leave geckos and anoles as the only known representatives of truly dry adhesive pads in nature. Engineers seeking biological inspiration for synthetic adhesives should consider whether model species with fluid secretions are appropriate to their

Inappropriate Tuberculosis Treatment Regimens in Chinese Tuberculosis Hospitals

NARCIS (Netherlands)

Xue He, Guang; van den Hof, Susan; van der Werf, Marieke J.; Guo, Hui; Hu, Yuan Lian; Fan, Ji Huan; Zhang, Wei Min; Tostado, Christopher P.; Borgdorff, Martien W.

2011-01-01

This investigation of tuberculosis (TB) treatment regimens in 6 TB hospitals in China showed that only 18% of patients with new cases and 9% of patients with retreatment cases were prescribed standard TB treatment regimens. Adherence to treatment guidelines needs to be improved in TB hospitals to

Friction and Braking Application of Unhazardous Palm Slag Brake Pad Composite

Science.gov (United States)

Khoni, Norizzahthul Ainaa Abdul; Ruzaidi Ghazali, Che Mohd; Bakri Abdullah, Mohd Mustafa Al

2018-03-01

This paper reveals new alternative friction materials for brake pads. Palm slag was studied as new friction materials in brake pads but its much harder made it difficult to be applied. As a way to reduce the hardness, tire dust was including as purpose on stabilizing the hardness of brake pads. The palm slag was sieves to get desired size that is 150 μm, 300 μm and 600 μm. The percentage weight of materials used are 20% graphite, 20% aluminium oxide, 20% steel fiber, 20% polyester resin and another 40% are varied between tire dust and palm slag. All of materials were blend and compress by using hot pressed machine. The composites properties that were examined are density, porosity, hardness, compressive strength, microstructure analysis and wear rate. The composition of 30% palm slag, 10% tire dust and larger size of filler give better result of mechanical properties and less wear rate of brake pads composites. Then, palm slag can be used in producing of non asbestos brake pads.

Prophylactic antibiotic regimens in tumour surgery (PARITY)

DEFF Research Database (Denmark)

Petersen, Michael Mørk; Hettwer, Werner H; Grum-Schwensen, Tomas

2015-01-01

-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. METHODS: We performed a pilot international multi-centre RCT. We used central randomisation...... to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. RESULTS: We screened 96 patients and enrolled 60 participants......% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. CONCLUSIONS: It is feasible to conduct a definitive multi-centre RCT of post...

Implementation Factors and Faculty Perceptions of Electronic Textbooks on the iPad

Science.gov (United States)

Rogers-Estable, Michelle Dawn

2018-01-01

A federally managed university in the United Arab Emirates implemented a one-to-one iPad program. In an effort to increase access to interactive digital learning resources on the iPads, they next transitioned from paperbased textbooks (pTexts) to electronic textbooks (eTexts) on the iPad for all course delivery formats. The goal of this study was…

Een jaar later, onderzoek naar de implementatie van de iPad bij het Leeuwarder Lyceum : Een vervolgonderzoek naar het iPad-gebruik onder leerlingen en leraren van het Leeuwarder Lyceum

NARCIS (Netherlands)

Stephanie Nijssen; Klaas Jan Huizing

2013-01-01

In september 2012 is de iPad geïmplementeerd in het onderwijs van het Leeuwarder Lyceum. Sowijs onderzocht tijdens de implementatie welke verwachtingen leerlingen en leraren hadden van de iPad. Nu, een jaar later, hebben we opnieuw onderzoek gedaan onder leerlingen en leraren naar het iPad-gebruik.

A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study.

Science.gov (United States)

Fenske, Timothy S; Shah, Namrata M; Kim, Kyung Mann; Saha, Sandeep; Zhang, Chong; Baim, Arielle E; Farnen, John P; Onitilo, Adedayo A; Blank, Jules H; Ahuja, Harish; Wassenaar, Tim; Qamar, Rubina; Mansky, Patrick; Traynor, Anne M; Mattison, Ryan J; Kahl, Brad S

2015-10-01

Proteasome inhibitors and mammalian target of rapamycin inhibitors each have activity in various B-cell malignancies and affect distinct cellular pathways. Their combination has demonstrated synergy in vitro and in mouse models. The authors conducted a single-arm, phase 2 trial of combined temsirolimus and bortezomib in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (NHL) using a dosing scheme that was previously tested in multiple myeloma. The patients received bortezomib and temsirolimus weekly on days 1, 8, 15, and 22 of a 35-day cycle. Of 39 patients who received treatment, 3 achieved a complete response (7.7%; 95% confidence interval [CI], 1.6%-21%), and 9 had a partial response (PR) (23%; 95% CI, 11%-39%). Thus, the overall response rate (12 of 39 patients) was 31% (95% CI, 17%-48%), and the median progression-free survival was 4.7 months (95% CI, 2.1-7.8 months; 2 months for patients with diffuse large B-cell lymphoma [n = 18], 7.5 months for those with mantle cell lymphoma [n = 7], and 16.5 months for those with follicular lymphoma [n = 9]). Two extensively treated patients with diffuse large B-cell lymphoma achieved a complete response. There were no unexpected toxicities from the combination. The current results demonstrate that the combination of a mammalian target of rapamycin inhibitor and a proteasome inhibitor is safe and has activity in patients with heavily pretreated B-cell NHL. Further studies with this combination are warranted in specific subtypes of NHL. © 2015 American Cancer Society.

Quantum One-Time Pad in the Presence of an Eavesdropper

Science.gov (United States)

Brandão, Fernando G. S. L.; Oppenheim, Jonathan

2012-01-01

A classical one-time pad allows two parties to send private messages over a public classical channel—an eavesdropper who intercepts the communication learns nothing about the message. A quantum one-time pad is a shared quantum state which allows two parties to send private messages or private quantum states over a public quantum channel. If the eavesdropper intercepts the quantum communication she learns nothing about the message. In the classical case, a one-time pad can be created using shared and partially private correlations. Here we consider the quantum case in the presence of an eavesdropper, and find the single-letter formula for the rate at which the two parties can send messages using a general quantum state as a quantum one-time pad. Surprisingly, the formula coincides with the distillable entanglement assisted by a symmetric channel, an important quantity in quantum information theory, but which lacked a clear operational meaning.

Contact statuses between functionally graded brake disk and pure pad disk

International Nuclear Information System (INIS)

Shahzamanian, M.M.; Sahari, B.B.; Bayat, M.; Mustapha, F.; Ismarrubie, Z.N.; Shahrjerdi, A.

2009-01-01

Full text: The contact statuses between functionally graded (FG) brake disks and pure pad disk are investigated by using finite element method (FEM). Two types of variation is considered for FG brake disk, the variation of materials are considered change in radial and thickness direction of disk. The material properties of these two types of FG brake disks are assumed to be represented by power-law distributions in the radius and thickness direction. The results are obtained and then compared. For the radial FG brake disk, the inner and outer surfaces are considered metal and ceramic respectively, and friction coefficient between metal surface and ceramic surface of FG brake dick with pad are considered 1.4 and 0.75 respectively. For the thickness FG brake disk the contact surface with pure pad brake disk is ceramic and the free surface is metal and friction coefficient between ceramic (contact) surface and pure pad brake disk is considered 0.75. In both types of FG brake disks the Coulomb contact friction is applied. Mechanical response of FG brake disks are compared and verified with the known results in the literatures. Three types of contact statuses are introduced as Sticking, Contact and Near Contact. The contact status between pad and disk for different values for pad thickness, grading index,n , and percentage of friction coefficient (λ) is shown. It can be seen that for all values of percentage of friction coefficient,λ , and grading indices, n, by increasing the thickness of pad cause the contact status changes from sticking to contact and then to near contact. (author)

Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.

Science.gov (United States)

Leonard, John P; Kolibaba, Kathryn S; Reeves, James A; Tulpule, Anil; Flinn, Ian W; Kolevska, Tatjana; Robles, Robert; Flowers, Christopher R; Collins, Robert; DiBella, Nicholas J; Papish, Steven W; Venugopal, Parameswaran; Horodner, Andrew; Tabatabai, Amir; Hajdenberg, Julio; Park, Jaehong; Neuwirth, Rachel; Mulligan, George; Suryanarayan, Kaveri; Esseltine, Dixie-Lee; de Vos, Sven

2017-11-01

Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m 2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

The effects of porosity in friction performance of brake pad using waste tire dust

Directory of Open Access Journals (Sweden)

İbrahim Mutlu

2015-10-01

Full Text Available Abstract This research is focused on the effect of porosity on the friction-wear properties of automotive brake pads. Waste Tire Dust (WTD was used as a new friction material in brake pads. Newly formulated brake pad materials with five different components have been produced by conventional techniques. In the experimental studies, the change of the friction coefficient, the temperature of the friction surface, the specific wear rate, and the hardness, density and porosity were measured. In addition, the micro-structural characterizations of brake pads are determined using Scanning Electron Microscopy (SEM. The mean coefficient of friction, porosity and specific wear are increased due to a WTD rate increases, on the other hand, hardness and density are decreased. As a result, WTD can be considered as an alternative to revalorize this kind of waste products in the brake pads and the amount of porosity of the brake pad affected the friction coefficient and wear behavior of the pad.

Dew point effect of cooled hydrogel pads on human stratum corneum biosurface.

Science.gov (United States)

Xhauflaire-Uhoda, Emmanuelle; Paquet, Philippe; Piérard, Gérald E

2008-01-01

Cooled hydrogel pads are used to prevent overheating effects of laser therapy. They do not induce cold injuries to the skin, but their more subtle physiological effects have not been thoroughly studied. To describe the changes in transepidermal water loss and electrometric properties of the skin surface following application of cooled hydrogel pads. Measurements were performed on normal forearm skin of 27 healthy volunteers and on freshly excised skin from abdominoplasty. LaserAid hydrogel pads cooled to 4 degrees C were placed for 15 min on the forearm skin. Measurements of transepidermal water loss (TEWL) and electrometric properties (Corneometer, Nova DPM 900) were performed before application and after removal of the cooled pads. A consistent increase in corneometer units, dermal phase meter (DPM) values and TEWL were recorded at removal of the cooled hydrogel pads. Both the in vivo and in vitro assessments brought similar information. The similar changes disclosed in vitro and in vivo suggest that a common physical process is operating in these conditions. The observed phenomenon is opposite to the predicted events given by the Arrhenius law probably because of the combination of cooling and occlusion by the pads. A dew point effect (air temperature at which relative humidity is maximal) is likely involved in the moisture content of the stratum corneum. Thus, the biological impact of using cooling hydrogel pads during laser therapy is different from the effect of a cryogenic spray cooling procedure. The better preservation of the water balance in the stratum corneum by the cooled hydrogel pads could have a beneficial esthetic effect on laser treated areas. (c) 2008 S. Karger AG, Basel.

The floating cardiac fat pad-sign of occult pneumothorax.

Science.gov (United States)

Kaufman, Claire; Bokhari, S A Jamal

2016-08-01

Pneumothoraces are a possible sequela of chest trauma with potential morbidity and mortality if not recognized and treated promptly. A portable supine chest radiograph is frequently the first radiologic study performed in the setting of trauma. While large pneumothoraces can be readily recognized on these radiographs, smaller pneumothoraces are missed in up to 15 % of trauma patients. There are many radiographic signs of occult pneumothoraces, and we are presenting a new radiographic sign of occult pneumothorax. The floating cardiac fat pad sign occurs when pleural air collects anteriorly and superiorly in the most non-dependent portion of the chest lifting the pericardial fat pad off the diaphragm. Lung markings are still seen surrounding the pericardial fat pad due to the inflated lower lobe of the lung resting dependently. Rapid and accurate identification of pneumothoraces is critical but often difficult on chest radiographs. Although there are many existing radiographic signs for identification of pneumothorax, prospective identification of small pneumothoraces is still relatively poor. Here, we describe an additional sign which aides in the detection of pneumothoraces, the floating cardiac fat pad. When present, this should prompt further evaluation with chest CT or upright chest radiograph.

Impact of the rail-pad multi-discrete model upon the prediction of the rail response

Science.gov (United States)

Mazilu, T.; Leu, M.

2017-08-01

Wheel/rail vibration has many technical effects such as wear of the rolling surfaces, rolling noise, settlement of the ballast and subgrade etc. This vibration is depending on the rail pad characteristic and subsequently, it is important to have an accurate overview on the relation between the rail pad characteristic and the level of the wheel/rail vibration. To this end, much theoretical and experimental research has been developed in the past, and for the theoretical approach the track model, in general, and, particularly, the rail pad model is of crucial importance. Usually, the rail pad model is discrete model one, neglecting the length of the rail pad. This fact is questionable because the sleepers span is only 4 times the rail pad length. Using the rail pad discrete model, the rail response is overestimated when the frequency of the excitation equals the pinned-pinned resonance frequency. In this paper, a multi-discrete model for the rail pad, consisting in many Kelvin-Voigt parallel systems, is inserted into an analytical model of the track. The track model is reduced to a rail taken as infinite Timoshenko beam, discretely supported via rail pad, sleeper and ballast. The influence of the number of Kelvin-Voigt systems of the rail pad model on the rail response is analysed.

Effect of Gender on Mechanical Properties of the Plantar Fascia and Heel Fat Pad.

Science.gov (United States)

Taş, Serkan

2017-10-01

The purpose of the study was to investigate the plantar fascia and heel fat pad stiffness and thickness parameters in females and compare these values with those of males. This study was carried out in 60 healthy sedentary participants (30 female, 30 male) between the ages of 19 and 50 years. Shear wave velocity (SWV) and thickness of the plantar fascia and heel fat pad were measured with an ultrasonography device. Males had a higher plantar fascia ( P = .037) and heel fat pad ( P = .001) thickness compared with females, but SWV of the plantar fascia ( P = .673), heel fat pad microchamber layer ( P = .240), and heel fat pad macrochamber layer ( P = .636) were similar in both groups. Body mass had a strong correlation with the plantar fascia ( r = 0.64, P plantar fascia ( r = 0.44, P Plantar fascia and heel fat pad stiffness were similar in both genders; however, females had a lower plantar fascia and heel fat pad thickness compared with males. Correlation analysis results suggest that higher plantar fascia and heel fat pad thickness in males may be related to higher body mass and height. Level III, Retrospective comparative study.

Assessment of non-standard HIV antiretroviral therapy regimens at ...

African Journals Online (AJOL)

2016-03-06

Mar 6, 2016 ... Most patients were transitioned to standard regimens, ... In cases of first-line regimen treatment failure, ..... tute; National Heart, Lung, and Blood Institute; National. Institute of Dental & Craniofacial Research; National Insti-.

How does the presence of excreta affect the behavior of laying hens on scratch pads?

Science.gov (United States)

Pokharel, B B; Boecker, I; Kwon, I Y; Jeyachanthiran, L; McBride, P; Harlander-Matauschek, A

2018-03-01

Enriched cages for laying hens provide scratch pads for foraging on the wire mesh floors. Apart from foraging on scratch pads, hens also defecate on these pads, causing them to become soiled with excreta. This study was conducted to determine the relative preference of laying hens for foraging on clean (C) scratch pads or scratch pads soiled with excreta (E), and to study the behaviors performed by hens on such pads. A total of 288 laying hens was housed in 16 enriched cages (18 hens/cage), each divided into 2 compartments. On a daily basis, half of the scratch pads (one in each compartment) were removed and cleaned, while the other half were cleaned and then covered with 550 g (0.35 g/cm2) of conspecific excreta. The C and E scratch pads were then put back into the cages in a systematic order to avoid side bias. Feed was delivered automatically onto the scratch pads as a litter substrate. The frequency of visits and the total time spent performing different behaviors on C and E pads were video-recorded [the time of video recording was relative to litter (feed) delivery on the scratch pads] for a total of 10 min/d, 3 times/wk, over a period of 4 weeks. Overall, the allocation of the time budget for different behaviors was found to be-in order of greatest to least amount of time-resting, locomotor behaviors (walking and running), foraging, and dust bathing. Laying hens showed a relative preference for E scratch pads by visiting them more frequently (P = 0.001), and spent more time (P = 0.035) foraging on them, whereas they rested for more time (P hens. Similarly, the longer use of C scratch pads for resting indicates the need for an ideal and clean resting surface in enriched cages.

A Study on quality improvement and application technology in pad-mounted transformers

Energy Technology Data Exchange (ETDEWEB)

Kim, Soon Tae; Mun, Kyung Hwa; Jung, Dong Won; Kim, Sang Jun; Lee, Nam Woo; Kang, Nae Kuk; Kim, Dong Mung [Korea Electric Power Corp. (KEPCO), Taejon (Korea, Republic of). Research Center; Kim, Kwang Ha; Kang, Young Sik; Lee, Woo Young; Lyu, Hee Suk; Sun, Jong Ho; Lyu, Hyung Ki; Kim, Yik Soo; Park, Sung Jae; Kim, Won Ho [Korea Electrotechnology Research Inst., Changwon (Korea, Republic of)

1995-12-31

In order to increase the reliability of pad-mounted transformers, the authors investigated operating condition of pad-mounted transformers and understood their failure mechanisms. The objective of their study was to improve quality and operating condition and install switches to be able to check and maintain transformers and optimise protection devices and increase cooling effect in pad-mounted transformers (author). 65 refs., 130 figs.

Toxicity and mutagenicity of low-metallic automotive brake pad materials.

Science.gov (United States)

Malachova, Katerina; Kukutschova, Jana; Rybkova, Zuzana; Sezimova, Hana; Placha, Daniela; Cabanova, Kristina; Filip, Peter

2016-09-01

Organic friction materials are standardly used in brakes of small planes, railroad vehicles, trucks and passenger cars. The growing transportation sector requires a better understanding of the negative impact related to the release of potentially hazardous materials into the environment. This includes brakes which can release enormous quantities of wear particulates. This paper addresses in vitro detection of toxic and mutagenic potency of one model and two commercially available low-metallic automotive brake pads used in passenger cars sold in the EU market. The model pad made in the laboratory was also subjected to a standardized brake dynamometer test and the generated non-airborne wear particles were also investigated. Qualitative "organic composition" was determined by GC/MS screening of dichloromethane extracts. Acute toxicity and mutagenicity of four investigated sample types were assessed in vitro by bioluminescence assay using marine bacteria Vibrio fischeri and by two bacterial bioassays i) Ames test on Salmonella typhimurium His(-) and ii) SOS Chromotest using Escherichia coli PQ37 strain. Screening of organic composition revealed a high variety of organic compounds present in the initial brake pads and also in the generated non-airborne wear debris. Several detected compounds are classified by IARC as possibly carcinogenic to humans, e. g. benzene derivatives. Acute toxicity bioassay revealed a response of bacterial cells after exposure to all samples used. Phenolic resin and wear debris were found to be acutely toxic; however in term of mutagenicity the response was negative. All non-friction exposed brake pad samples (a model pad and two commercial pad samples) were mutagenic with metabolic activation in vitro. Copyright © 2016 Elsevier Inc. All rights reserved.

The SciencePAD treasure hunt of Persistent Identifiers

CERN Multimedia

Beatrice Bressan, for the European Middleware Initiative (EMI)

2013-01-01

Have you ever followed a reference for an article that eventually turned out to be unavailable? Have you always thought that experiment data or research results should be permanently accessible? If so, you will probably be interested in the latest news on the current status of software and digital information issues, and you shouldn’t miss the SciencePAD Persistent Identifiers Workshop (SPID2013).   The workshop is being organised by the European Middleware Initiative (EMI) together with its SciencePAD (formerly known as ScienceSoft) project and will take place on 30 January 2013 at CERN. SciencePAD is a community-enabler, working on providing the necessary one-stop-shop tools, including software, catalogues, statistics, reference citation systems, marketplaces, technical services links, platform integration supports, etc. It allows researchers and open source software developers from scientific communities to interact with each other within and beyond their area of expertise, and co...

A Scott bench with ergonomic thorax stabilisation pad improves body posture during preacher arm curl exercise.

Science.gov (United States)

Biscarini, Andrea; Benvenuti, Paolo; Busti, Daniele; Zanuso, Silvano

2016-05-01

We assessed whether the use of an ergonomic thorax stabilisation pad, during the preacher arm curl exercise, could significantly reduce the excessive shoulder protraction and thoracic kyphosis induced by the standard flat pad built into the existing preacher arm curl equipment. A 3D motion capture system and inclinometers were used to measure shoulder protraction and thoracic kyphosis in 15 subjects performing preacher arm curl with a plate-loaded machine provided with the standard flat pad. The same measures were repeated after replacing the flat pad with a new ergonomic pad, specifically designed to accommodate the thorax profile and improve body posture. Pad replacement significantly (p ergonomic pad may potentially allow a more effective training, prevent musculoskeletal discomfort and reduce the risk of injury. Practitioner summary: We have designed an ergonomic thorax stabilisation pad for the preacher arm curl exercise. The new ergonomic pad improves the poor posture conditions induced by the standard flat pad and may potentially allow a more effective training, prevent musculoskeletal discomfort, improve the breathing function and reduce the risk of injury.

The PAD Class: a new paradigm for university classroom teaching

Science.gov (United States)

Zhang, Xuexin

2017-08-01

The PAD Class (Presentation-Assimilation-Discussion) is a new paradigm for classroom teaching combining strengths of lecture and discussion. With half class time allocated for teacher's presentation and the other half for students' discussion, an assimilation stage was inserted between presentation and discussion for independent and individualized learning. Since its first success in 2014, the PAD method has gained national popularity in China and been successfully put into practice by thousands of college teachers in nearly all subjects, e.g., science, engineering, medical sciences, social sciences, humanities and arts. This paper analyzed the psychological and pedagogical rationales underlying the PAD Class to explicate its effectiveness in enhancing active learning.

Construction and characterization of the TL/TH thorium calibration pads

International Nuclear Information System (INIS)

Steele, W.D.

1987-09-01

The Technical Measurements Center (TMC) was established and was tasked with developing and/or recommending measurement methods for use in support of remedial action programs. Since one aspect of this technical support is the provision of calibration facilities for standardization of field measurements, four sets of thorium-232 enriched pads (two pads per set) were constructed for use by remedial action contractors in calibrating portable field instruments that are used to make direct, in-situ measurements of radium-226, thorium-232, and potassium-40. This report presents the design, construction, and characterization data of the eight calibration pads. 17 refs., 8 figs., 15 tabs

Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma.

Science.gov (United States)

Usmani, S Z; Cavenagh, J D; Belch, A R; Hulin, C; Basu, S; White, D; Nooka, A; Ervin-Haynes, A; Yiu, W; Nagarwala, Y; Berger, A; Pelligra, C G; Guo, S; Binder, G; Gibson, C J; Facon, T

2016-01-01

To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective. A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually. Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes. Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio

Towards reducing impact-induced brain injury: lessons from a computational study of army and football helmet pads.

Science.gov (United States)

Moss, William C; King, Michael J; Blackman, Eric G

2014-01-01

We use computational simulations to compare the impact response of different football and U.S. Army helmet pad materials. We conduct experiments to characterise the material response of different helmet pads. We simulate experimental helmet impact tests performed by the U.S. Army to validate our methods. We then simulate a cylindrical impactor striking different pads. The acceleration history of the impactor is used to calculate the head injury criterion for each pad. We conduct sensitivity studies exploring the effects of pad composition, geometry and material stiffness. We find that (1) the football pad materials do not outperform the currently used military pad material in militarily relevant impact scenarios; (2) optimal material properties for a pad depend on impact energy and (3) thicker pads perform better at all velocities. Although we considered only the isolated response of pad materials, not entire helmet systems, our analysis suggests that by using larger helmet shells with correspondingly thicker pads, impact-induced traumatic brain injury may be reduced.

The Tablet Inscribed: Inclusive Writing Instruction with the iPad

Science.gov (United States)

Sullivan, Rebecca M.

2013-01-01

Despite the author's initial skepticism, a classroom set of iPads has reinforced a student-directed approach to writing instruction, while also supporting an inclusive classroom. Using the iPads, students guide their writing process with access to the learning management system, electronic information resources, and an online text editor. Students…

SCIENTIFIC PROGRESS OF THE MC-PAD NETWORK

CERN Document Server

Aguilar, J; Ambalathankandy, P; Apostolakis, J; Arora, R; Balog, T; Behnke, T; Beltrame, P; Bencivenni, G; Caiazza, S; Dong, J; Heller, M; Heuser, J; Idzik, M; Joram, C; Klanner, R; Koffeman, E; Korpar, S; Kramberger, G; Lohmann, W; Milovanović, M; Miscetti, S; Moll, M; Novgorodova, O; Pacifico, N; Pirvutoiu, C; Radu, R; Rahman, S; Rohe, T; Ropelewski, L; Roukoutakis, F; Schmidt, C; Schön, R; Sibille, J; Tsagri, M; Turala, M; Van Beuzekom, M; Verheyden, R; Villa, M; Zappon, F; Zawiejski, L; Zhang, J

2013-01-01

MC-PAD is a multi-site Initial Training Network on particle detectors in physics experiments. It comprises nine academic participants, three industrial partners and two associated academic partners. 17 recruited Early Stage and 5 Experienced Researchers have performed their scientific work in the network. The research and development work of MC-PAD is organized in 12 work packages, which focus on a large variety of aspects of particle detector development, electronics as well as simulation and modelling. The network was established in November 2008 and lasted until October 2012 (48 months). This report describes the R&D activities and highlights the main results achieved during this period.

Use of an iPad to Provide Warfarin Video Education to Hospitalized Patients.

Science.gov (United States)

Kim, Jenny Jane; Mohammad, Rima A; Coley, Kim C; Donihi, Amy C

2015-09-01

To evaluate the effectiveness of a warfarin educational video in the hospital setting and to determine patients' satisfaction with using an iPad to view a warfarin educational video. This prospective quality improvement project included adult (≥18 years of age) patients on warfarin in the hospital. All patients completed pre-video and post-video knowledge tests on the iPad before and after viewing the educational video on warfarin therapy. Patients also completed a patient satisfaction survey. Forty hospitalized patients were educated using the warfarin video and included for analysis. The majority of patients were new to warfarin therapy (65%). Forty-three percent of patients passed the pre-video knowledge test, and 90% passed the post-video knowledge test (P iPad and found it easy to use. Patients who were younger (iPad more than older patients (P = 0.01) and male subjects (P = 0.02), respectively. Also, younger patients found the iPad easier to use compared with patients who were older (P = 0.01). Educating hospitalized patients about warfarin by using a video on an iPad was effective. Video education on an iPad may be an alternative to traditional education in the hospital setting.

Knee Fat Pad Volumes in Patients with Hemophilia and Their Relationship with Osteoarthritis

Directory of Open Access Journals (Sweden)

Annette von Drygalski

2017-01-01

Full Text Available Hemophilic arthropathy is a progressive, disabling condition with poorly understood pathobiology. Since there is an emerging interest to study the role of intra-articular fat pad size and biology in arthritic conditions, we explored fat pad volume changes in hemophilic arthropathy and to what extent they differed from osteoarthritis. We matched a cohort of 13 adult patients with hemophilic arthropathy of the knee with age- and gender-matched cohorts without osteoarthritis (“control cohort” and with the same degree of radiographic osteoarthritis (“OA cohort” in 1 : 2 fashion. Infrapatellar fat pad (IPFP and suprapatellar fat pad (SPFP volumes were calculated based on magnetic resonance imaging and differences in fat pad volumes, demographics, height, weight, and osteoarthritis scores were evaluated. Fat pad volumes were positively associated with body size parameters in all three cohorts but were unaffected by the degree of osteoarthritis. While IPFP volumes did not differ between cohorts, SPFP volumes expanded disproportionally with weight in hemophilia patients. Our observations indicate that IPFPs and SPFPs behave biologically differently in response to different arthritic stimuli. The exaggerated expansion of the SPFP in hemophilia patients highlights the importance of further studying the implications of fat pad biology for progression of hemophilic arthropathy.

TID Test Results for 4th Generation iPad(TradeMark)

Science.gov (United States)

Guertin, S. M.; Allen, G. R.; McClure, S. S.; LaBel, K. A.

2013-01-01

TID testing of 4th generation iPads is reported. Of iPad subsystems, results indicate that the charging circuitry and display drivers fail at lowest TID levels. Details of construction are investigated for additional testing of components.

On the comparison between MRI and US imaging for human heel pad thickness measurements

DEFF Research Database (Denmark)

Matteoli, Sara; Corbin, Nadège Corbin; Wilhjelm, Jens E.

2011-01-01

The human heel pad thickness, defined as the shortest distance between the calcaneus and heel skin, is one of the intrinsic factor which must be taken into account when investigating the biomechanics of the heel pad. US and MRI are the preferable imaging modalities used to measure the heel pad...... thickness as they are both ionizing-free radiations. The aim of this paper is to measure the bone to skin distance of nine heel pad phantoms from MRI and US images, and to compare the results with a true value (TV) in order to find the errors. Paired sample t-test was used to compare the measurements......1530 (P-value=0.402). Results confirm the necessity to investigate on the real speed of sound for the heel pad tissues, in order to have realistic measurements when dealing with human heel pads. __________________________________________________________________________________________________________...

SCiPad: Effective Implementation of Telemedicine Using iPads with Individuals with Spinal Cord Injuries, a Case Series

Directory of Open Access Journals (Sweden)

Kazuko Shem

2017-05-01

Full Text Available BackgroundIndividuals with spinal cord injury (SCI must often travel long distances to see a rehabilitation specialist. While telemedicine (TM for pressure ulcer management has been used in this population, real-time video telecommunication using iPad has never been described.ObjectiveThe objective of this study was to provide specialized care for persons with SCI through TM consultation expediently in order to address medical needs, manage secondary complications, and to improve quality of life (QoL of individuals with SCI.MethodsTen individuals with SCI participated in the TM program using iPads for 6 months as a feasibility study at a single-center, county hospital. The participants contacted the project staff for SCI-related conditions and were then connected to an SCI-trained health-care provider within 24 hours via FaceTime. Main outcome measures included health-care utilization; QoL and psychosocial measures collected at baseline and at 6 months: Reintegration to Normal Living Index (RNLI, Life Satisfaction Index A (LSI-A, and Patient Health Questionnaire 9 (PHQ-9; and a Program Satisfaction Survey.ResultsTen patients (seven with tetraplegia, three with paraplegia; eight males and two females with an average age of 34.4 (18–54 years were enrolled. The average baseline and 6-month follow-up scores were RNLI—70.1 ± 19.7 and 74.7 ± 21.8, respectively; LSI-A—25.4 ± 7.4 and 26.4 ± 8.2, respectively; and PHQ-9 were 6.8 ± 7.2 and 8.6 ± 6.1, respectively. TM encounters included topics such as pain, bladder and skin management, medication changes, and lab results. The Program Satisfaction Survey yielded positive results with 100% of program completers stating they would recommend the program and would like to continue having TM.ConclusionThis is the first known successful project using iPad to provide TM in the SCI population. This study discusses the implementation of such a TM program in a health system

Metal-core pad-plane development for ACTAR TPC

Science.gov (United States)

Giovinazzo, J.; Pibernat, J.; Goigoux, T.; de Oliveira, R.; Grinyer, G. F.; Huss, C.; Mauss, B.; Pancin, J.; Pedroza, J. L.; Rebii, A.; Roger, T.; Rosier, P.; Saillant, F.; Wittwer, G.

2018-06-01

With the recent development of active targets and time projection chambers (ACTAR TPC) as detectors for fundamental nuclear physics experiments, the need arose for charge collection planes with a high density of readout channels. In order to fulfill the mechanical constraints for the ACTAR TPC device, we designed a pad-plane based on a metal-core circuit with an conceptually simple design and routing for signal readout, named FAKIR (in reference to a fakir bed of nails). A test circuit has been equipped with a micro mesh gaseous structure (micromegas) for signal amplification and a dedicated readout electronics. Test measurements have been performed with an 55Fe X-ray source giving an intrinsic energy resolution (FWHM) of 22 ± 1% at 5 . 9 keV, and with a 3-alpha source for which a resolution of about 130 ± 20 keV at 4 . 8 MeV has been estimated. The pad-plane has been mounted into a reduced size demonstrator version of the ACTAR TPC detector, in order to illustrate charged particle track reconstruction. The tests preformed with the X-ray and the 3-alpha sources shows that results obtained from pads signals are comparable to the intrinsic result from the micro-mesh signal. In addition, a simple alpha particle tracks analysis is performed to demonstrate that the pad plane allows a precise reconstruction of the direction and length of the trajectories.

The Neglected "R": Improving Writing Instruction through iPad Apps

Science.gov (United States)

Sessions, Laird; Kang, Mi Ok; Womack, Sue

2016-01-01

In this study the authors investigated the effects of integrating iPad applications into writing instruction for fifth grade students. By comparing the writing of students taught with paper and pencil methods with that of students utilizing the iPad writing applications, two research questions guided the study: (1) Are there differences in student…

An algorithm for nonlinear thermal analysis of fuel bearing pads

International Nuclear Information System (INIS)

Attia, M.H.; D'Silva, N.

1983-01-01

An algorithm has been developed for accurate prediction of the temperature field in a CANDU fuel bearing pad and the extent of the nucleate boiling in the crevice region. The methodology recognizes the nonlinear nature of the problem due to the fact that local boiling is both controlling and being controlled by the conditions of heat transfer at the boundaries. The finite difference model accounts for the volumetric effect of the thermal contact resistance at the bearing pad/pressure tube interface. It also allows the evaluation of the thermal barrier effect caused by applying an oxide film on the radiused surface of the bearing pad. Information pertaining to the distribution of the coefficient of heat transfer over water-cooled surfaces has been generated. Analysis of the results indicated the significance of considering the nonlinear behaviour of the system in determining its state of equilibrium. It also indicated that, depending on the thickness of the oxide layer and the position of the bearing pad along the core of the reactor, the nucleate boiling process can be prevented

Construction and characterization of the RH/RL radium calibration pads

International Nuclear Information System (INIS)

Steele, W.D.; Marutzky, S.J.; Dickerson, J.W.

1989-01-01

The US Department of Energy (DOE) Office of Remedial Action and Waste Technology has as one of its goals the standardization of field measurements made by its remedial action contractors throughout the country. In support of this goal, the Technical Measurements Center (TMC) was established at the DOE Grand Junction Projects Office (GJPO) Facility, and was tasked with developing and/or recommending measurement methods for use in support of remedial action programs. One aspect of this technical support is the provision of calibration facilities for standardization of field measurements. The report presents the results of the design, construction, and characterization of 14 calibration pads enriched in radium-226. The 14 pads comprise 7 sets with a high and low activity pad in each set. The pads are concrete cylinders, approximately 5 feet in diameter by 2 feet in height. They are intended for use in calibrating portable field instruments that are used by remedial action contractors to make direct, in situ measurements of radium-226, thorium-232, and potassium-40. 23 refs., 6 figs., 14 tabs

Efficacy and toxicity profile of carfilzomib based regimens for treatment of multiple myeloma: A systematic review.

Science.gov (United States)

Mushtaq, Adeela; Kapoor, Vikas; Latif, Azka; Iftikhar, Ahmad; Zahid, Umar; McBride, Ali; Abraham, Ivo; Riaz, Irbaz Bin; Anwer, Faiz

2018-05-01

Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of Doceri Software for iPad in Online Delivery of Chemistry Content

Science.gov (United States)

Silverberg, Lee J.; Tierney, John; Bodek, Matthew J.

2014-01-01

Doceri software for iPad is useful for both synchronous online and asynchronous online delivery of chemistry course content. Using the Doceri wireless connection between the iPad and a personal computer that is running Adobe Connect, online synchronous instruction can be accomplished in which drawings can be completed by hand on the iPad. For…

Exploring the Use of the iPad for Literacy Learning

Science.gov (United States)

Hutchison, Amy; Beschorner, Beth; Schmidt-Crawford, Denise

2012-01-01

The goal of this investigation was to explore how a fourth grade teacher could integrate iPads into her literacy instruction to simultaneously teach print-based and digital literacy goals. The teacher used iPads for a three-week period during her literacy instruction and selected apps that provided unique approaches to helping the students meet…

Another Perspective: The iPad Is a REAL Musical Instrument

Science.gov (United States)

Williams, David A.

2014-01-01

This article looks at the iPad's role as a musical instrument through the lens of a live performance ensemble that performs primarily on iPads. It also offers an overview of a pedagogical model used by this ensemble, which emphasizes musician autonomy in small groups, where music is learned primarily through aural means and concerts are…

Engaging Organic Chemistry Students Using ChemDraw for iPad

Science.gov (United States)

Morsch, Layne A.; Lewis, Michael

2015-01-01

Drawing structures, mechanisms, and syntheses is a vital part of success in organic chemistry courses. ChemDraw for iPad has been used to increase classroom experiences in the preparation of high quality chemical drawings. The embedded Flick-to-Share allows for simple, real-time exchange of ChemDraw documents. ChemDraw for iPad also allows…

Improvement of Thrust Bearing Calculation Considering the Convectional Heating within the Space between the Pads

OpenAIRE

Monika Chmielowiec-Jablczyk; Andreas Schubert; Christian Kraft; Hubert Schwarze; Michal Wodtke; Michal Wasilczuk

2018-01-01

A modern thrust bearing tool is used to estimate the behavior of tilting pad thrust bearings not only in the oil film between pad and rotating collar, but also in the space between the pads. The oil flow in the space significantly influences the oil film inlet temperature and the heating of pad and collar. For that reason, it is necessary to define an oil mixing model for the space between the pads. In the bearing tool, the solutions of the Reynolds equation including a cavitation model, the ...

ATLANTIS ROLLS OUT TO PAD 39A FOLLOWING HURRICANE FRAN THREAT

Science.gov (United States)

1996-01-01

A view from the flame trench looking up shows the Space Shuttle Atlantis, mounted on the Mobile Launcher Platform and Crawler- Transporter, as it arrives atop the hardstand at Launch Pad 39A. After the Shuttle and launch stand are in position, the crawler will be pulled back. This is the third time Atlantis has completed the journey to Launch Pad 39A in the STS-79 mission flow. The Shuttle was rolled back from the pad in July due to the threat from Hurricane Bertha, then rolled back again earlier this week because of Hurricane Fran. The targeted launch date for Atlantis on Mission STS-79 -- the fourth docking between the U.S. Shuttle and Russian Space Station Mir -- is now Sept. 16 at 4:54 a.m. EDT. The three rollout dates for Atlantis to Pad 39A are: July 1, Aug. 20 and Sept. 5.

University staff adoption of iPads: An empirical study using an extended TAM model

Directory of Open Access Journals (Sweden)

Michael Steven Lane

2014-11-01

Full Text Available This research examined key factors influencing adoption of iPads by university staff. An online survey collected quantitative data to test hypothesised relationships in an extended TAM model. The findings show that university staff consider iPads easy to use and useful, with a high level of compatibility with their work. Social status had no influence on their attitude to using an iPad. However older university staff and university staff with no previous experience in using a similar technology such as an iPhone or smartphone found iPads less easy to use. Furthermore, a lack of formal end user ICT support impacted negatively on the use of iPads.

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

Science.gov (United States)

Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E; Sanderson, Michael W; Bodie, Wesley W; Kramer, Lora B; Orlowski, Robert Z; Grant, Steven

2014-01-01

The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

Directory of Open Access Journals (Sweden)

Xin-Yan Pei

Full Text Available The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

Science.gov (United States)

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-06-03

To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

A hinged-pad test structure for sliding friction measurement in micromachining

Energy Technology Data Exchange (ETDEWEB)

Boer, M.P. de; Redmond, J.M.; Michalske, T.A.

1998-08-01

The authors describe the design, modeling, fabrication and initial testing of a new test structure for friction measurement in MEMS. The device consists of a cantilevered forked beam and a friction pad attached via a hinge. Compared to previous test structures, the proposed structure can measure friction over much larger pressure ranges, yet occupies one hundred times less area. The placement of the hinge is crucial to obtaining a well-known and constant pressure distribution in the device. Static deflections on the device were measured and modeled numerically, Preliminary results indicate that friction pad slip is sensitive to friction pad normal force.

MWPC with highly segmented cathode pad readout

International Nuclear Information System (INIS)

Debbe, R.; Fischer, J.; Lissauer, D.

1989-01-01

Experiments being conducted with high energy heavy ion beams at Brookhaven National Laboratory and at CERN have shown the importance of developing position sensitive detectors capable of handling events with high multiplicity in environments of high track density as will also be the case in future high luminosity colliders like SSC and RHIC. In addition, these detectors are required to have a dynamic range wide enough to detect minimum ionizing particles and heavy ions like oxygen or silicon. We present here a description of work being done on a prototype of such a detector at BNL. Results from a similar counter are also presented in this Conference. The ''pad chamber'' is a detector with a cathode area subdivided into a very large number of pixel-like elements such that a charged particle traversing the detector at normal incidence leaves an induced charge on a few localized pads. The pads are interconnected by a resistive strip, and readout amplifiers are connected to the resistive strip at appropriate, carefully determined spacings. The pattern of tracks in a multi-hit event is easily recognized, and a centroid-finding readout system allows position determination to a small fraction of the basic cell size. 5 refs., 9 figs

Improvement of Thrust Bearing Calculation Considering the Convectional Heating within the Space between the Pads

Directory of Open Access Journals (Sweden)

Monika Chmielowiec-Jablczyk

2018-02-01

Full Text Available A modern thrust bearing tool is used to estimate the behavior of tilting pad thrust bearings not only in the oil film between pad and rotating collar, but also in the space between the pads. The oil flow in the space significantly influences the oil film inlet temperature and the heating of pad and collar. For that reason, it is necessary to define an oil mixing model for the space between the pads. In the bearing tool, the solutions of the Reynolds equation including a cavitation model, the energy equation and the heat transfer equation are done iteratively with the finite volume method by considering a constant flow rate. Both effects—laminar/turbulent flow and centrifugal force—are considered. The calculation results are compared with measurements done for a flooded thrust bearing with nominal eight tilting pads with an outer diameter of 180 mm. The heat convection coefficients for the pad surfaces mainly influence the pad temperature field and are adjusted to the measurement results. In the following paper, the calculation results for variable space distances, influence of different parameters on the bearing behavior and operating condition at high load are presented.

Placement of the Left Side AED Pad is Poor: Training on the Left Compared to the Right Side of a Manikin Does Not Improve Pad Placement

DEFF Research Database (Denmark)

Stærk, Mathilde; Bødtker, Henrik; Rahbek, Søren

2015-01-01

participating in a first aid course were randomized to learn automated external defibrillation sitting on the left or right side of a manikin during AED training. After course completion participants operated a training AED (Lifepak® CR-T AED Trainer, PhysioControl) and placed AED pads according to instructions...... volunteers were included and randomized to AED training on the left (n=14, 43% male, age: 47.9 years) and right (n=16, 25% male, age: 46.7 years) side of a manikin. There was no difference in left pad placement when trained on the left or right side (distance to recommended left apical pad position (mean...

Development of antibiotic regimens using graph based evolutionary algorithms.

Science.gov (United States)

Corns, Steven M; Ashlock, Daniel A; Bryden, Kenneth M

2013-12-01

This paper examines the use of evolutionary algorithms in the development of antibiotic regimens given to production animals. A model is constructed that combines the lifespan of the animal and the bacteria living in the animal's gastro-intestinal tract from the early finishing stage until the animal reaches market weight. This model is used as the fitness evaluation for a set of graph based evolutionary algorithms to assess the impact of diversity control on the evolving antibiotic regimens. The graph based evolutionary algorithms have two objectives: to find an antibiotic treatment regimen that maintains the weight gain and health benefits of antibiotic use and to reduce the risk of spreading antibiotic resistant bacteria. This study examines different regimens of tylosin phosphate use on bacteria populations divided into Gram positive and Gram negative types, with a focus on Campylobacter spp. Treatment regimens were found that provided decreased antibiotic resistance relative to conventional methods while providing nearly the same benefits as conventional antibiotic regimes. By using a graph to control the information flow in the evolutionary algorithm, a variety of solutions along the Pareto front can be found automatically for this and other multi-objective problems. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

Science.gov (United States)

Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

2015-01-01

Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative regimens of a variety of other hematological and non-hematological malignancies. The addition of newer agents to conditioning like bortezomib or lenalidomide for myeloma, or clofarabine for myeloid malignancies, may improve antitumor effects for transplantation, while in combination with alemtuzumab may represent a backbone for future cellular therapy due to reliable engraftment and low toxicity profile. This review summarizes the development and the current use of this remarkable drug in hematopoietic stem-cell transplantation. PMID:22922522

Focused Molding Using Adhesive Pads in Mehta Casting for Early-Onset Scoliosis.

Science.gov (United States)

Abraham, Roby; Sponseller, Paul D

2014-11-01

Prospective clinical series. To determine the effect of adhesive pads placed over the apex of scoliosis curves on curve correction 1) after the first cast and 2) after the final cast. Early-onset scoliosis is often effectively managed by serial casting. Properly localizing the apex of the molds with the cast in place is challenging. The authors explored the effectiveness of a novel technique: incorporation of adhesive pads placed over the major curve apex before Mehta casting. The 27 patients who received body casts (2000-2013) were divided into 2 groups: those without and with apical adhesive pads (5-6 layers of pads placed on the major curve's apex during casting): non-pad (NP) group (n = 12) and pad (P) group (n = 15), respectively. Groups were compared regarding the percentage of Cobb angle change from the first cast and curve correction to a Cobb angle of cast curve correction was 39% ± 18% and 56% ± 17% in the NP and P groups, respectively. Of the 26 patients out of a cast, 11 (42%) had a Cobb angle of casting were effective in increasing the amount of major curve correction from the first cast for idiopathic early-onset scoliosis and in decreasing curves to <25° at final follow-up. Copyright © 2014 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Expanding the role of the iPad and tablet devices to cosmetic patient consultations.

Science.gov (United States)

Wang, Jing; Hsu, Jeffrey T S; Bhatia, Ashish C

2012-09-01

The iPad is a useful reference tool for patient education in cosmetic consultations. In this article, we plan to (1) discuss how the iPad can be implemented and used by patients and physicians in consultations, (2) compare the advantages and disadvantages of the iPad with other forms of technology, (3) discuss the optimal way of using the iPad for patient care, (4) see how this tool complies with privacy regulations, and (5) look at other uses of the iPad in the patient care setting. There has been positive feedback from both patients and physicians regarding the addition of the tablet computer during consultations. In addition to showing patients pictures of cosmetic procedures, the iPad also has various multimedia capabilities such as videos and drawing tools that are useful in optimizing patient satisfaction, increasing clinical efficacy, and improving the overall patient experience. Copyright © 2012. Published by Elsevier Inc.

Kinetic energy absorbing pad

International Nuclear Information System (INIS)

Bricmont, R.J.; Hamilton, P.A.; Ming Long Ting, R.

1981-01-01

Reactors, fuel processing plants etc incorporate pipes and conduits for fluids under high pressure. Fractures, particularly adjacent to conduit elbows, produce a jet of liquid which whips the broken conduit at an extremely high velocity. An enormous impact load would be applied to any stationary object in the conduit's path. The design of cellular, corrugated metal impact pads to absorb the kinetic energy of the high velocity conduits is given. (U.K.)

Lateral Vibration of Hydroelectric Generating Set with Different Supporting Condition of Thrust Pad

Directory of Open Access Journals (Sweden)

Xiaohui Si

2011-01-01

Full Text Available The variations of the supporting condition, which change the stiffness of tilting pad thrust bearing, may alter the dynamic behavior of the rotor system. The effects of supporting condition of thrust pad on the lateral vibration of a hydroelectric generating set are investigated in this paper. The action of a thrust bearing is described as moments acting on the thrust collar, and the tilting stiffness coefficients of thrust bearing are calculated. A model based on typical beam finite element method is established to calculate the dynamic response, and the effects of supporting conditions such as elastic oil tank support, different heights of the thrust pads with rigid support are discussed. The results reveal that the influence of thrust bearing is small when the elastic oil tanks work normally. When the supporting conditions turn to be rigid due to the oil leakage, the differences of thrust pad heights have evident influence on the load distribution of the thrust pads; while the effects on the tilting stiffness of the thrust bearing and the amplitude of the lateral shaft vibration is small when the maximum load on thrust pads is smaller than the allowable value.

Method for Producing Launch/Landing Pads and Structures Project

Science.gov (United States)

Mueller, Robert P. (Compiler)

2015-01-01

Current plans for deep space exploration include building landing-launch pads capable of withstanding the rocket blast of much larger spacecraft that that of the Apollo days. The proposed concept will develop lightweight launch and landing pad materials from in-situ materials, utilizing regolith to produce controllable porous cast metallic foam brickstiles shapes. These shapes can be utilized to lay a landing launch platform, as a construction material or as more complex parts of mechanical assemblies.

ClimatePad: Enabling public exploration of climate data

Science.gov (United States)

Walsh, J. E.; Chapman, W. L.

2012-12-01

Informal learners interested in climate issues can find a wealth of information in the print and online media related to climate and climate change. Throughout these resources, the equal use of generic terms like 'global warming' and 'climate change' suggest a level of nuance in the science that is not easy to convey in this conventional media. Perhaps more than any other discipline, climate literacy has the most potential to be enhanced via the process of cognitive construction and reconstruction, rather than simple transmission of knowledge. Constructionism suggests that meaningful learning happens most effectively if the learner is actively engaged in constructing a product in the real world rather than absorbing information passively. Recent technological innovations have introduced mobile computing devices with sufficient power to do serious data analysis. The potential of these devices to augment climate literacy by turning citizens into scientists has yet to be exploited. We introduce ClimatePad, an iPad application that permits students and public to actively browse climate datasets, construct trends, plot time series, create composite differences and view animations of real-world climate data. Interactions with the ClimatePad permits varying the starting and ending dates of trends and differences. Climate analysis maps and animations can be customized with different color palettes, enticing the user to delve into and absorb the subtleties of the regional and temporal variations of the recent climate record. Finally, user-generated climate visualizations created with ClimatePad can be emailed to friends and shared via Facebook, entraining even more active learners.

Direct application of Padé approximant for solving nonlinear differential equations.

Science.gov (United States)

Vazquez-Leal, Hector; Benhammouda, Brahim; Filobello-Nino, Uriel; Sarmiento-Reyes, Arturo; Jimenez-Fernandez, Victor Manuel; Garcia-Gervacio, Jose Luis; Huerta-Chua, Jesus; Morales-Mendoza, Luis Javier; Gonzalez-Lee, Mario

2014-01-01

This work presents a direct procedure to apply Padé method to find approximate solutions for nonlinear differential equations. Moreover, we present some cases study showing the strength of the method to generate highly accurate rational approximate solutions compared to other semi-analytical methods. The type of tested nonlinear equations are: a highly nonlinear boundary value problem, a differential-algebraic oscillator problem, and an asymptotic problem. The high accurate handy approximations obtained by the direct application of Padé method shows the high potential if the proposed scheme to approximate a wide variety of problems. What is more, the direct application of the Padé approximant aids to avoid the previous application of an approximative method like Taylor series method, homotopy perturbation method, Adomian Decomposition method, homotopy analysis method, variational iteration method, among others, as tools to obtain a power series solutions to post-treat with the Padé approximant. 34L30.

Physicochemical characterization of cactus pads from Opuntia dillenii and Opuntia ficus indica.

Science.gov (United States)

Méndez, Lorena Pérez; Flores, Fidel Tejera; Martín, Jacinto Darias; Rodríguez Rodríguez, Elena M; Díaz Romero, Carlos

2015-12-01

Physicochemical characteristics (weight, length, width, thickness, moisture, Brix degree, total fiber, protein, ash, pH, acidity, ascorbic acid, total phenolic compounds, P, Na, K, Ca, Mg, Fe, Cu, Zn, Mn and Cr) were determined in cactus pads from Opuntia dillenii and Opuntia ficus indica. The physicochemical characteristics of both species were clearly different. There were important differences between the orange and green fruit pulp of O. ficus indica; the cactus pads of O. dillenii could be differentiated according to the region (North and South). Consumption of cactus pads contributes to the intake of dietary fiber, total phenolic compounds, K, Mg, Mn and Cr. Applying factor and/or discriminant analysis, the cactus pad samples were clearly differentiated according to the species, the fruit pulp color and production region. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characteristics of HIV antiretroviral regimen and treatment adherence

Directory of Open Access Journals (Sweden)

Vera Lúcia da Silveira

Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

Change in ploidy status from hyperdiploid to near-tetraploid in multiple myeloma associated with bortezomib/lenalidomide resistance.

Science.gov (United States)

Pavlistova, Lenka; Zemanova, Zuzana; Sarova, Iveta; Lhotska, Halka; Berkova, Adela; Spicka, Ivan; Michalova, Kyra

2014-01-01

Ploidy is an important prognostic factor in the risk stratification of multiple myeloma (MM) patients. Patients with MM can be divided into two groups according to the modal number of chromosomes: nonhyperdiploid (NH-MM) and hyperdiploid (H-MM), which has a more favorable outcome. The two ploidy groups represent two different oncogenetic pathways determined at the premalignant stage. The ploidy subtype also persists during the course of the disease, even during progression after the therapy, with only very rare cases of ploidy conversion. The clinical significance of ploidy conversion and its relation to drug resistance have been previously discussed. Here, we describe a female MM patient with a rare change in her ploidy status from H-MM to NH-MM, detected by cytogenetic and molecular cytogenetic examinations of consecutive bone marrow aspirates. We hypothesize that ploidy conversion (from H-MM to NH-MM) is associated with disease progression and acquired resistance to bortezomib/lenalidomide therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Dermal exposure assessment to benzene and toluene using charcoal cloth pads

NARCIS (Netherlands)

Wendel de Joode, B. van; Tielemans, E.; Vermeulen, R.; Wegh, H.; Kromhout, H.

2005-01-01

Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and

Measuring contact area in a sliding human finger-pad contact.

Science.gov (United States)

Liu, X; Carré, M J; Zhang, Q; Lu, Z; Matcher, S J; Lewis, R

2018-02-01

The work outlined in this paper was aimed at achieving further understanding of skin frictional behaviour by investigating the contact area between human finger-pads and flat surfaces. Both the static and the dynamic contact areas (in macro- and micro-scales) were measured using various techniques, including ink printing, optical coherence tomography (OCT) and Digital Image Correlation (DIC). In the studies of the static measurements using ink printing, the experimental results showed that the apparent and the real contact area increased with load following a piecewise linear correlation function for a finger-pad in contact with paper sheets. Comparisons indicated that the OCT method is a reliable and effective method to investigate the real contact area of a finger-pad and allow micro-scale analysis. The apparent contact area (from the DIC measurements) was found to reduce with time in the transition from the static phase to the dynamic phase while the real area of contact (from OCT) increased. The results from this study enable the interaction between finger-pads and contact object surface to be better analysed, and hence improve the understanding of skin friction. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model.

Directory of Open Access Journals (Sweden)

Emily A Kendall

2017-01-01

Full Text Available Novel drug regimens are needed for tuberculosis (TB treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen's ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective.We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis, South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS or rifampicin-resistant (RR TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1 efficacy, (2 duration, (3 ease of adherence, (4 medical contraindications, (5 barrier to resistance, and (6 baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113-187 and 16 (95% UR: 9-23 per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4-10 and 0.6 (95% UR: 0.3-1.1 per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%-20% and 11% (95% UR: 6%-20%, respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%-46% and RR TB mortality by 30% (95% UR: 18%-44%. Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99% reduced TB mortality by 6% (95% UR: 1%-13%, half the

The use of an iPad to collect patient-reported functional outcome measures in hand surgery.

Science.gov (United States)

Yaffe, Mark; Goyal, Nitin; Kokmeyer, Daniel; Merrell, Gregory A

2015-09-01

The purpose of this study was to evaluate (1) patient preferences regarding iPad and paper-based questionnaires, (2) the efficacy of iPad and paper questionnaires in a hand surgery practice, (3) the influence of questionnaire length on patient preferences and data collection, and (4) patient characteristics associated with a preference for iPad-based questionnaires. Two hundred total patients in a single hand surgery practice were randomly assigned to one of four groups. Each group completed either the Michigan Hand Questionnaire (MHQ) or QuickDASH (QD) using either an iPad or pen and paper. Patient preferences, questionnaire completion and timing, and demographic data were analyzed. The use of an iPad was associated with a statistically stronger preference for the same delivery format in the future compared to paper for the MHQ (93.9 vs 52.1 %, p iPad group found the survey "physically easy" more often compared to the MHQ paper group, while no difference was found among QD groups. Questionnaire timing between iPad and paper groups was similar for the MHQ but statistically longer with the iPad for QD. A significantly higher proportion of patients who preferred the iPad were under the age of 50 compared to those who preferred paper. The addition of an iPad is an efficient and preferable questionnaire format for functional outcome assessment in a hand and upper extremity surgery practice setting. The iPad is particularly preferable for longer outcome questionnaires and for patients under the age of 50.

Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

Science.gov (United States)

Neu, A; Lange, K; Barrett, T; Cameron, F; Dorchy, H; Hoey, H; Jarosz-Chobot, P; Mortensen, H B; Robert, J-J; Robertson, K; de Beaufort, C

2015-09-01

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Antimony leaching release from brake pads: Effect of pH, temperature and organic acids.

Science.gov (United States)

Hu, Xingyun; He, Mengchang; Li, Sisi

2015-03-01

Metals from automotive brake pads pollute water, soils and the ambient air. The environmental effect on water of antimony (Sb) contained in brake pads has been largely untested. The content of Sb in one abandoned brake pad reached up to 1.62×10(4) mg/kg. Effects of initial pH, temperature and four organic acids (acetic acid, oxalic acid, citric acid and humic acid) on Sb release from brake pads were studied using batch reactors. Approximately 30% (97 mg/L) of the total Sb contained in the brake pads was released in alkaline aqueous solution and at higher temperature after 30 days of leaching. The organic acids tested restrained Sb release, especially acetic acid and oxalic acid. The pH-dependent concentration change of Sb in aqueous solution was best fitted by a logarithmic function. In addition, Sb contained in topsoil from land where brake pads were discarded (average 9×10(3) mg/kg) was 3000 times that in uncontaminated soils (2.7±1 mg/kg) in the same areas. Because potentially high amounts of Sb may be released from brake pads, it is important that producers and environmental authorities take precautions. Copyright © 2015. Published by Elsevier B.V.

Cement-base bearing pads mortar for connections in the precast concrete: study of surface roughness

Directory of Open Access Journals (Sweden)

M. K. El Debs

Full Text Available Bearing pads are used in precast concrete connections to avoid concentrated stresses in the contact area between the precast elements. In the present research, the bearing pads are Portland cement mortar with styrene-butadiene latex (SB, lightweight aggregate (expanded vermiculite-term and short fibers (polypropylene, glass and PVA, in order to obtain a material with low modulus of elasticity and high tenacity, compared with normal Portland cement mortar. The objective of this paper is to analyze the influence of surface roughness on the pads and test other types of polypropylene fibers. Tests were carried out to characterize the composite and test on bearing pads. Characterization tests show compressive strength of 41MPa and modulus of elasticity of 12.8GPa. The bearing pads tests present 30% reduction of stiffness in relation to a reference mortar. The bearing pads with roughness on both sides present a reduction up to 30% in stiffness and an increase in accumulated deformation of more than 120%, regarding bearing pads with both sides smooth.

Mobile Tech and the Librarian: The iTest iPad Project.

Science.gov (United States)

Hamasu, Claire; Bramble, John

A 2012 project provided forty-eight health sciences librarians from primarily hospital and academic health sciences libraries with an Apple iPad2 along with training and support on its use. Project objectives were to determine how participants would adopt the iPad into their daily operations and what form of leadership role they would play while participating in the project. By project's end eighty-nine percent indicated they would continue using the iPad primarily as a productivity tool and to provide point of need services. Project data indicated that librarians assumed a leadership role promoting the use of mobile technology and the applications available.

Mobile Tech and the Librarian: The iTest iPad Project

Science.gov (United States)

Hamasu, Claire; Bramble, John

2015-01-01

A 2012 project provided forty-eight health sciences librarians from primarily hospital and academic health sciences libraries with an Apple iPad2 along with training and support on its use. Project objectives were to determine how participants would adopt the iPad into their daily operations and what form of leadership role they would play while participating in the project. By project's end eighty-nine percent indicated they would continue using the iPad primarily as a productivity tool and to provide point of need services. Project data indicated that librarians assumed a leadership role promoting the use of mobile technology and the applications available. PMID:26997921

An approach to evaluate capacitance, capacitive reactance and resistance of pivoted pads of a thrust bearing

Science.gov (United States)

Prashad, Har

1992-07-01

A theoretical approach is developed for determining the capacitance and active resistance between the interacting surfaces of pivoted pads and thrust collar, under different conditions of operation. It is shown that resistance and capacitive reactance of a thrust bearing decrease with the number of pads times the values of these parameters for an individual pad, and that capacitance increases with the number of pads times the capacitance of an individual pad. The analysis presented has a potential to diagnose the behavior of pivoted pad thrust bearings with the angle of tilt and the ratio of film thickness at the leading to trailing edge, by determining the variation of capacitance, resistance, and capacitive reactance.

Genital lesions: An indication for changing ART regimen.

Science.gov (United States)

Kumar, S Arun; Kumar, N; Kumarasamy, N

2011-01-01

Genital lesions are common in HIV positive patients and aetiology for these are mainly due to HSV, HPV or bacterial. They usually respond to HAART, antiviral or antimicrobials. We are presenting a young patient on HAART with non-healing genital ulcer lesions for sixteen months. He responded well to a change in ART regimen within a period of 15 days. This happened after a change to a more potent ART regimen.

Shock absorbency of factors in the shoe/heel interaction--with special focus on role of the heel pad.

Science.gov (United States)

Jørgensen, U; Bojsen-Møller, F

1989-06-01

The heel pad acts as a shock absorber in walking and in heel-strike running. In some patients, a reduction of its shock-absorbing capacity has been connected to the development of overuse injuries. In this article, the shock absorption of the heel pad as well as external shock absorbers are studied. Individual variation and the effect of trauma and confinement on the heel pad were specifically investigated. Drop tests, imitating heel impacts, were performed on a force plate. The test specimens were cadaver heel pads (n = 10); the shoe sole component consisted of ethyl vinyl acetate (EVA) foam and Sorbothane inserts. The shock absorption was significantly greater in the heel pad than in the external shock absorbers. The mean heel pad shock absorption was 1.1 times for EVA foam and 2.1 times for Sorbothane. The shock absorption varied by as much as 100% between heel pads. Trauma caused a decrease in the heel pad shock absorbency (24%), whereas heel pad confinement increased the shock absorbency (49% in traumatized heel pads and 29.5% in nontraumatized heel pads). These findings provide a biomechanical rationale for the clinical observations of a correlation between heel pad shock absorbency loss and heel strike-dependent overuse injuries. To increase shock absorbency, confinement of the heel pad should be attempted in vivo.

Next Generation Non-particulate Dry Nonwoven Pad for Chemical Warfare Agent Decontamination

Energy Technology Data Exchange (ETDEWEB)

Ramkumar, S S; Love, A; Sata, U R; Koester, C J; Smith, W J; Keating, G A; Hobbs, L; Cox, S B; Lagna, W M; Kendall, R J

2008-05-01

New, non-particulate decontamination materials promise to reduce both military and civilian casualties by enabling individuals to decontaminate themselves and their equipment within minutes of exposure to chemical warfare agents or other toxic materials. One of the most promising new materials has been developed using a needlepunching nonwoven process to construct a novel and non-particulate composite fabric of multiple layers, including an inner layer of activated carbon fabric, which is well-suited for the decontamination of both personnel and equipment. This paper describes the development of a composite nonwoven pad and compares efficacy test results for this pad with results from testing other decontamination systems. The efficacy of the dry nonwoven fabric pad was demonstrated specifically for decontamination of the chemical warfare blister agent bis(2-chloroethyl)sulfide (H or sulfur mustard). GC/MS results indicate that the composite fabric was capable of significantly reducing the vapor hazard from mustard liquid absorbed into the nonwoven dry fabric pad. The mustard adsorption efficiency of the nonwoven pad was significantly higher than particulate activated carbon (p=0.041) and was similar to the currently fielded US military M291 kit (p=0.952). The nonwoven pad has several advantages over other materials, especially its non-particulate, yet flexible, construction. This composite fabric was also shown to be chemically compatible with potential toxic and hazardous liquids, which span a range of hydrophilic and hydrophobic chemicals, including a concentrated acid, an organic solvent and a mild oxidant, bleach.

Eco-friendly asbestos free brake-pad: Using banana peels

Directory of Open Access Journals (Sweden)

U.D. Idris

2015-07-01

Full Text Available The use of asbestos fibre is being avoided due to its carcinogenic nature that might cause health risks. A new brake pad produced using banana peel waste to replace asbestos and Phenolic resin (phenol formaldehyde, as a binder was investigated. The resin was varying from 5 to 30 wt% with an interval of 5 wt%. Morphology, physical, mechanical and wear properties of the brake pad were studied. The results show that compressive strength, hardness and specific gravity of the produced samples were seen to be increasing with an increase in wt% of resin addition, while oil soak, water soak, wear rate and percentage charred decreased as the wt% of resin increased. Overall samples, containing 25 wt% in uncarbonized banana peels (BUNCp and 30 wt% in carbonized (BCp gave better properties. The result of this research indicates that banana peel particles can be effectively used as a replacement for asbestos in brake pad manufacture.

Aspects regarding manufacturing technologies of composite materials for brake pad application

Science.gov (United States)

Craciun, A. L.; Hepuţ, T.; Pinca-Bretotean, C.

2018-01-01

Current needs in road safety, requires the development of new technical solutions for automotive braking system. Their safe operation is subject to following factors: concept design, materials used and electronic control. Among the factors previously listed, choice of materials and manufacturing processes are difficult stage but very important for achieving technical performance and getting a relatively small cost of constituting parts of brake system. The choice is based on the promotion of organic composite material, popular in areas where the weight of materials plays an important role. The brake system is composed of many different parts including brake pads, a master cylinder, wheel cylinders and a hydraulic control system. The brake pads are an important component in the braking system of automotive. These are of different types, suitable for different types of automotive and engines. Brake pads are designed for friction stability, durability, minimization of noise and vibration. The typology of the brake pads depends on the material which they are made. The aim of this paper is to presents the manufacturing technologies for ten recipes of composite material used in brake pads applications. In this work will be done: choosing the constituents of the recipes, investigation of their basic characteristics, setting the proportions of components, obtaining the composite materials in laboratory, establishing the parameters of manufacturing technology and technological analysis.

iPad-based patient briefing for radiological examinations-a clinical trial.

Science.gov (United States)

Schlechtweg, Philipp M; Hammon, Matthias; Giese, David; Heberlein, Christian; Uder, Michael; Schwab, Siegfried A

2014-08-01

To analyze if an iPad-based patient briefing can serve as a digital alternative to conventional documentations prior to radiological examinations. One hundred one patients referred for routine MRI were randomized into two groups, who underwent iPad-based and classic written briefing in opposite order. For each briefing completion time, completeness and correctness were noted. Patient's knowledge about the content of either briefing modality was subsequently tested. The influence of patient-related factors on the performance of the electronic briefing (EB) was analyzed. Finally, the patient's subjective impression of the EB was assessed. The mean durations were 4.4 ± 2.2 min for EB and 1.7 ± 1.3 min for the classic briefing (p iPad briefings were returned entirely filled out, whereas 11 % of the classic forms were returned with missing data. No significant differences in memorization of the briefing's information were objectified. There was a positive correlation between the duration of EB and age (r = 0.53; p iPads transfers the information for the patients equally well compared to the classic written approach. Although iPad briefing took patients longer to perform, the majority would prefer it to written consent briefings in the future. Nevertheless, measures have to be undertaken to improve the overall acceptance and performance.

Reducing friction in tilting-pad bearings by the use of enclosed recesses

DEFF Research Database (Denmark)

Heinrichson, Niels; Santos, Ilmar

2008-01-01

A three-dimensional thermoelastohydrodynamic model is applied to the analysis of tilting-pad bearings with spherical pivots and equipped with deep recesses in the high-pressure regions. A potential for a 10-20% reduction in the friction loss compared to conventional plain bearing pads is documented....... Design suggestions minimizing the power loss are given for various length-to-width ratios. The tilting angle in the sliding direction is more sensitive to correct positioning of the pivot point than conventional bearing pads. Improving the performance by equipping a tilting-pad bearing with a deep recess...... therefore requires accurate analysis and design of the bearing. Similarly, a high sensitivity perpendicular to the sliding direction suggests that this method of reducing friction is more feasible when using line pivots or spring beds than when using spherical pivots for controlling the tilting angle....

Aggressive Regimens for Multidrug-Resistant Tuberculosis Reduce Recurrence

Science.gov (United States)

Franke, Molly F.; Appleton, Sasha C.; Mitnick, Carole D.; Furin, Jennifer J.; Bayona, Jaime; Chalco, Katiuska; Shin, Sonya; Murray, Megan; Becerra, Mercedes C.

2013-01-01

Background. Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. Methods. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. Results. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2–53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17–0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17–50.60]; P = .004). Conclusions. Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease. PMID:23223591

Fluid regimens for colostomy irrigation: a systematic review.

Science.gov (United States)

Lizarondo, Lucylynn; Aye Gyi, Aye; Schultz, Tim

2008-09-01

Background  Various techniques for managing faecal evacuation have been proposed; however, colostomy irrigation is favoured as it leads to better patient outcomes. Alternative fluid regimens for colostomy irrigation have been suggested to achieve effective evacuation. Aim  The objective of this review was to summarise the best available evidence on the most effective fluid regimen for colostomy irrigation. Search strategy  Trials were identified by electronic searches of CINAHL, PubMed, MEDLINE, Current Contents, the Cochrane Library and EMBASE. Unpublished articles and references lists from included studies were also searched. Selection criteria  Randomised controlled trials and before-and-after studies investigating any fluid regimen for colostomy irrigation were eligible for inclusion. Outcomes measured included fluid inflow time, total wash-out time, haemodynamic changes during irrigation, cramps, leakage episodes, quality of life and level of satisfaction. Data collection and analysis  Trial selection, quality appraisal and data extraction were carried out independently by two reviewers. Differences in opinion were resolved by discussion. Main results  The systematic literature search strategy identified two cross-over trials that compared water with another fluid regimen. Owing to the differences in irrigating solutions used, the results were not pooled for analysis. Both the polyethylene glycol electrolyte solution and glyceryl trinitrate performed significantly better than water. Conclusion  There is some evidence to support the effectiveness of fluid regimens other than water, such as polyethylene glycol electrolyte and glyceryl trinitrate, for colostomy irrigation. Further well-designed clinical trials are required to establish solid evidence on the effectiveness of other irrigating solutions that might enhance colonic irrigation. © 2008 The Authors. Journal Compilation © Blackwell Publishing Asia Pty Ltd.

Digital representation of oil and natural gas well pad scars in southwest Wyoming: 2012 update

Science.gov (United States)

Garman, Steven L.; McBeth, Jamie L.

2015-01-01

The recent proliferation of oil and natural gas energy development in the Greater Green River Basin of southwest Wyoming has accentuated the need to understand wildlife responses to this development. The location and extent of surface disturbance that is created by oil and natural gas well pad scars are key pieces of information used to assess the effects of energy infrastructure on wildlife populations and habitat. A digital database of oil and natural gas pad scars had previously been generated from 1-meter (m) National Agriculture Imagery Program imagery (NAIP) acquired in 2009 for a 7.7-million hectare (ha) (19,026,700 acres) region of southwest Wyoming. Scars included the pad area where wellheads, pumps, and storage facilities reside and the surrounding area that was scraped and denuded of vegetation during the establishment of the pad. Scars containing tanks, compressors, the storage of oil and gas related equipment, and produced-water ponds were also collected on occasion. This report updates the digital database for the five counties of southwest Wyoming (Carbon, Lincoln, Sublette, Sweetwater, Uinta) within the Wyoming Landscape Conservation Initiative (WLCI) study area and for a limited portion of Fremont, Natrona, and Albany Counties using 2012 1-m NAIP imagery and 2012 oil and natural gas well permit information. This report adds pad scars created since 2009, and updates attributes of all pad scars using the 2012 well permit information. These attributes include the origination year of the pad scar, the number of active and inactive wells on or near each pad scar in 2012, and the overall status of the pad scar (active or inactive). The new 2012 database contains 17,404 pad scars of which 15,532 are attributed as oil and natural gas well pads. Digital data are stored as shapefiles projected to the Universal Transverse Mercator (zones 12 and 13) coordinate system. These data are available from the U.S. Geological Survey (USGS) at http://dx.doi.org/10

Seismic tipping analysis of a spent nuclear fuel shipping cask sitting on a crush pad

International Nuclear Information System (INIS)

Uldrich, E.D.; Hawkes, B.D.

1998-04-01

A crush pad has been designed and analyzed to absorb the kinetic energy of an accidentally dropped spent nuclear fuel shipping cask into a 44 ft. deep cask unloading pool. Conventional analysis techniques available for evaluating a cask for tipping due to lateral seismic forces assume that the cask rests on a rigid surface. In this analysis, the cask (110 tons) sits on a stainless steel encased (0.25 in. top plate), polyurethane foam (4 ft. thick) crush pad. As the cask tends to rock due to horizontal seismic forces, the contact area between the cask and the crush pad is reduced, increasing the bearing stress, and causing the pivoting corner of the cask to depress into the crush pad. As the crush pad depresses under the cask corner, the pivot point shifts from the corner toward the cask center, which facilitates rocking and potential tipping of the cask. Subsequent rocking of the cask may deepen the depression, further contributing to the likelihood of cask tip over. However, as the depression is created, the crush pad is absorbing energy from the rocking cask. Potential tip over of the cask was evaluated by performing a non-linear, dynamic, finite element analysis with acceleration time history input. This time history analysis captured the effect of a deforming crush pad, and also eliminated conservatisms of the conventional approaches. For comparison purposes, this analysis was also performed with the cask sitting on a solid stainless steel crush pad. Results indicate that the conventional methods are quite conservative relative to the more exacting time history analysis. They also indicate that the rocking motion is less on the foam crush pad than on the solid stainless steel pad

iPad colour vision apps for dyschromatopsia screening.

Science.gov (United States)

Campbell, Thomas Gordon; Lehn, Alexander; Blum, Stefan; Airey, Caroline; Brown, Helen

2016-07-01

Optic neuritis (ON) is a common and important cause of vision loss or vision disturbances in the community, particularly amongst the young, and it is often associated with a persistent dyschromatopsia. Traditionally screening for dyschromatopsia has been carried out using pseudo-isochromatic Ishihara plates. These colour plates were originally developed for testing of colour blindness, and indeed have only more recently been applied to ON. As the Ishihara plate books used for testing are expensive, unwieldy, and are not commonly available in many clinics or wards, many neurologists and ophthalmologists have taken to using untested and unstudied downloadable software packages on portable electronic devices for testing. This study compared the efficacy of printed and iPad (Apple, Cupertino, CA, USA) versions of the Ishihara plates in screening for dyschromatopsia in patients who were suspected of having ON. The main finding was that dyschromatopsia testing using a commercially available application on an iPad was comparable to using the current pragmatic clinical benchmark, the pseudo-isochromatic plates of Ishihara. These findings provide support for the increasingly common practice of screening for dyschromatopsia using the iPad. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparing performance on the MNREAD iPad application with the MNREAD acuity chart.

Science.gov (United States)

Calabrèse, Aurélie; To, Long; He, Yingchen; Berkholtz, Elizabeth; Rafian, Paymon; Legge, Gordon E

2018-01-01

Our purpose was to compare reading performance measured with the MNREAD Acuity Chart and an iPad application (app) version of the same test for both normally sighted and low-vision participants. Our methods included 165 participants with normal vision and 43 participants with low vision tested on the standard printed MNREAD and on the iPad app version of the test. Maximum Reading Speed, Critical Print Size, Reading Acuity, and Reading Accessibility Index were compared using linear mixed-effects models to identify any potential differences in test performance between the printed chart and the iPad app. Our results showed the following: For normal vision, chart and iPad yield similar estimates of Critical Print Size and Reading Acuity. The iPad provides significantly slower estimates of Maximum Reading Speed than the chart, with a greater difference for faster readers. The difference was on average 3% at 100 words per minute (wpm), 6% at 150 wpm, 9% at 200 wpm, and 12% at 250 wpm. For low vision, Maximum Reading Speed, Reading Accessibility Index, and Critical Print Size are equivalent on the iPad and chart. Only the Reading Acuity is significantly smaller (I. E., better) when measured on the digital version of the test, but by only 0.03 logMAR (p = 0.013). Our conclusions were that, overall, MNREAD parameters measured with the printed chart and the iPad app are very similar. The difference found in Maximum Reading Speed for the normally sighted participants can be explained by differences in the method for timing the reading trials.

Diagnostic procedure on brake pad assembly based on Young's modulus estimation

International Nuclear Information System (INIS)

Chiariotti, P; Santolini, C; Tomasini, E P; Martarelli, M

2013-01-01

Quality control of brake pads is an important issue, since the pad is a key component of the braking system. Typical damage of a brake pad assembly is the pad–backing plate detachment that affects and modifies the mechanical properties of the whole system. The most sensitive parameter to the damage is the effective Young's modulus, since the damage induces a decrease of the pad assembly stiffness and therefore of its effective Young's modulus: indeed its variation could be used for diagnostic purposes. The effective Young's modulus can be estimated from the first bending resonance frequency identified from the frequency response function measured on the pad assembly. Two kinds of excitation methods, i.e. conventional impulse excitation and magnetic actuation, will be presented and two different measurement sensors, e.g. laser Doppler vibrometer and microphone, analyzed. The robustness of the effective Young's modulus as a diagnostic feature will be demonstrated in comparison to the first bending resonance frequency, which is more sensitive to geometrical dimensions. Variability in the sample dimension, in fact, will induce a variation of the resonance frequency which could be mistaken for damage. The diagnostic approach has been applied to a set of undamaged and damaged pad assemblies showing good performance in terms of damage identification. The environmental temperature can be an important interfering input for the diagnostic procedure, since it influences the effective Young's modulus of the assembly. For that reason, a test at different temperatures in the range between 15 °C and 30 °C has been performed, evidencing that damage identification technique is efficient at any temperature. The robustness of the Young's modulus as a diagnostic feature with respect to damping is also presented. (paper)

Office for iPad and Mac for dummies

CERN Document Server

Weverka, Peter

2015-01-01

The easy way to work with Office on your iPad or Mac Are you a Mac user who isn't accustomed to working with Microsoft Office? Consider this friendly guide your go-to reference! Written in plain English and packed with easy-to-follow, step-by-step instructions, Office for iPad and Mac For Dummies walks you through every facet of Office, from installing the software and opening files to working with Word, Excel, PowerPoint, and Outlook-and beyond. Plus, you'll discover how to manage files, share content and collaborate online through social media, and find help when you need it. Two things a

Design of a digital PAD based on I/Q demodulation principle

International Nuclear Information System (INIS)

Geng Zheqiao; Cui Yanyan; Hou Mi; Pei Guoxi

2005-01-01

Conventional analog I/Q demodulator suffers from phase and amplitude imbalance and DC offset, which cause big error into the measurement. A digital PAD is designed. Based on I/Q demodulation principle, using digital algorithms, such as digital filter and Hilbert transform, the conventional measurement error can basically be removed. Measuremental results show that the digital PAD has a maximum phase error of ±0.5 degree and a resolution of 0.2 degree. Its temperature coefficient is -0.1 degree/degree C. Its dynamic ranges for phase-measurement and amplitude-measurement are -1825 dBm and -2020 dBm, respectively. The digital PAD can meet the need of the BEPC II phasing system. (authors)

Study on Load-displacement Test of Rubber Pads of Coal Mine Roadway Constructed by Shield

Science.gov (United States)

Yang, Yue; Chen, Xiaoguo; Yang, Liyun

2017-12-01

Shield method construction of coal mine roadway is the future trend of the development of deep coal mining. The main shaft supporting is the segment. There is rubber pads between segment and segment. The performance of compression deformation of rubber pad is essential for the overall stability of lining. Through load test, displacement of the rubber pad under load, the thrust force law of the rubber pad deformation, and provide a theoretical basis for the stability analysis of coal mine tunnel shield construction.

Population-based evaluation of the effectiveness of two regimens for emergency contraception.

Science.gov (United States)

Leung, Vivian W Y; Soon, Judith A; Lynd, Larry D; Marra, Carlo A; Levine, Marc

2016-06-01

To estimate and compare the effectiveness of the levonorgestrel and Yuzpe regimens for hormonal emergency contraception in routine clinical practice. A retrospective population-based study included women who accessed emergency contraceptives for immediate use prescribed by community pharmacists in British Columbia, Canada, between December 2000 and December 2002. Linked administrative healthcare data were used to discern the timings of menses, unprotected intercourse, and any pregnancy-related health services. A panel of experts evaluated the compatibility of observed pregnancies with the timing of events. The two regimens were compared with statistical adjustments for potential confounding. Among 7493 women in the cohort, 4470 (59.7%) received levonorgestrel and 3023 (40.3%) the Yuzpe regimen. There were 99 (2.2%) compatible pregnancies in the levonorgestrel group and 94 (3.1%) in the Yuzpe group (P=0.017). The estimated odds ratio for levonorgestrel compared with the Yuzpe regimen after adjusting for potential confounders was 0.64 (95% confidence interval 0.47-0.87). Against an expected pregnancy rate of approximately 5%, the relative and absolute risk reductions were 56.0% and 2.8%, respectively, for levonorgestrel and 36.7% and 1.8% for the Yuzpe regimen. The levonorgestrel regimen is more effective than the Yuzpe regimen in routine use. The data suggest that both regimens are less effective than has been observed in randomized trials. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Does It Matter Whether One Takes a Test on an iPad or a Desktop Computer?

Science.gov (United States)

Ling, Guangming

2016-01-01

To investigate possible iPad related mode effect, we tested 403 8th graders in Indiana, Maryland, and New Jersey under three mode conditions through random assignment: a desktop computer, an iPad alone, and an iPad with an external keyboard. All students had used an iPad or computer for six months or longer. The 2-hour test included reading, math,…

Examining Teachers' Use of iPads: Comfort Level, Perception, and Use

Science.gov (United States)

Liu, Min; Navarrete, Cesar C.; Scordino, Robert; Kang, Jina; Ko, Yujung; Lim, Mihyun

2016-01-01

While there is evidence of the growing popularity of iPads and other tablets in K-12 education, little is understood about how teachers use these devices in their instruction. This study examines 342 teachers' comfort level with and perception toward iPad use and any changes that occurred over the implementation year. Using a mixed-methods design,…

Rancang Bangun Modul PAD (Packet Assembler Dissassembler Menggunakan AX.25 pada Sistem Komunikasi ITS-SAT

Directory of Open Access Journals (Sweden)

Pasang Arung Padang

2013-09-01

Full Text Available ITS-Sat merupakan jenis satelit piko yang saat ini sedang dikembangkan di Institut Teknologi Sepuluh Nopember. ITS-Sat membutuhkan suatu protokol komunikasi yang mengatur tata cara komunikasi satelit. Protokol AX.25 merupakan protokol komunikasi yang digunakan dalam sistem komunikasi ITS-Sat. Protokol ini berada pada layer data link dalam model OSI Layer. Protokol ini dapat membangun dan memutuskan link serta melakukan pengiriman data. Protokol AX.25 menggabungkan data-data field menjadi suatu frame. Makalah ini mengimplementasikan protokol AX.25 ke dalam modul PAD (Packet Assembler Dissassembler. Protokol AX.25 diimplementasikan ke dalam mikrokontroler yang merupakan otak dari modul PAD dengan menggunakan bahasa pemograman. Modul PAD berfungsi untuk mengkapsulasi data tiap field menjadi sebuah frame AX.25 sebelum dikirim dan kemudian frame AX.25 yang diterima dienkapsulasi kembali menjadi data field. Modul PAD yang dibuat dapat mengirim dan menerima data teks sebanyak 500 karakter. Hasil pengujian menunjukan bahwa modul PAD yang dibuat mampu melakukan komunikasi antar modul PAD dengan baik.

Quantitative evaluation of the pivot shift by image analysis using the iPad.

Science.gov (United States)

Hoshino, Yuichi; Araujo, Paulo; Ahldén, Mattias; Samuelsson, Kristian; Muller, Bart; Hofbauer, Marcus; Wolf, Megan R; Irrgang, James J; Fu, Freddie H; Musahl, Volker

2013-04-01

To enable comparison of test results, a widely available measurement system for the pivot shift test is needed. Simple image analysis of lateral knee joint translation is one such system that can be installed on a prevalent computer tablet (e.g. iPad). The purpose of this study was to test a novel iPad application to detect the pivot shift. It was hypothesized that the abnormal lateral translation in ACL deficient knees would be detected by the iPad application. Thirty-four consecutive ACL deficient patients were tested. Three skin markers were attached on the following bony landmarks: (1) Gerdy's tubercle, (2) fibular head and (3) lateral epicondyle. A standardized pivot shift test was performed under anaesthesia, while the lateral side of the knee joint was monitored. The recorded movie was processed by the iPad application to measure the lateral translation of the knee joint. Lateral translation was compared between knees with different pivot shift grades. Valid data sets were obtained in 20 (59 %) ACL deficient knees. The remaining 14 data sets were invalid because of failure to detect translation or detection of excessive translation. ACL deficient knees had larger lateral translation than the contra-lateral knees (p iPad application, the potential of the iPad application to classify the pivot shift was demonstrated.

Monte Carlo studies on Cathode Strip/Pad Chambers for the ALICE Di-Muon Arm

Energy Technology Data Exchange (ETDEWEB)

Wurzinger, R.; Le Bornec, Y.; Willis, N.

1996-04-01

A general overview about the properties of Cathode Strip and Pad Chambers is given. Position finding methods are discussed and compared within Monte Carlo studies. Noise contributions and their minimization are discussed. Pad chambers allow a two-dimensional readout with spatial resolution of {sigma} < 100 {mu}m in direction parallel to the anode wire. The resolution normal to the anode wire depends mainly on the wire spacing. Special attention is paid on the double-hit resolution capability of the pad chamber. An outlook is given on the possible utilisation of Cathode Pad Chambers in the Di-Muon Arm of the ALICE detector at LHC. (author). 44 refs.

[Mantle cell lymphoma: Towards a personalized therapeutic strategy?].

Science.gov (United States)

Navarro Matilla, Belén; García-Marco, José A

2015-06-22

Mantle cell lymphoma (MCL) is a clinically heterogeneous non-Hodgkin lymphoma with an aggressive clinical behaviour and short survival in some cases and an indolent course in others. Advances in the biology and pathogenesis of MCL have unveiled several genes involved in deregulation of cell cycle checkpoints and the finding of subclonal populations with specific recurrent mutations (p53, ATM, NOTCH2) with an impact on disease progression and refractoriness to treatment. Prognostic stratification helps to distinguish between indolent and aggressive forms of MCL. Currently, younger fit patients benefit from more intensive front line chemotherapy regimens and consolidation with autologous transplantation, while older or frail patients are treated with less intensive regimens and rituximab maintenance. For relapsing disease, the introduction of bortezomib and lenalidomide containing regimens and B-cell receptor pathway inhibitors such as ibrutinib and idelalisib in combination with immunochemotherapy have emerged as therapeutic agents with promising clinical outcomes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Inflammatory and metabolic alterations of Kager's fat pad in chronic achilles tendinopathy

DEFF Research Database (Denmark)

Pingel, Jessica; Petersen, Marie Christine Helby; Fredberg, Ulrich

2015-01-01

Kager's fat pad and its surrounding structures during movement of the ankle, suggesting that Kager's fat pad may stabilize and protect the mechanical function of the ankle joint. AIM: The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression...

Development of a hadron blind detector using a finely segmented pad readout

International Nuclear Information System (INIS)

Kanno, Koki; Aoki, Kazuya; Aramaki, Yoki; En'yo, Hideto; Kawama, Daisuke; Komatsu, Yusuke; Masumoto, Shinichi; Nakai, Wataru; Obara, Yuki; Ozawa, Kyoichiro; Sekimoto, Michiko; Shibukawa, Takuya; Takahashi, Tomonori; Watanabe, Yosuke; Yokkaichi, Satoshi

2016-01-01

We constructed a hadron blind detector (HBD) using a finely segmented pad readout. The finely segmented pad readout enabled us to adopt an advanced particle identification method which applies a threshold to the number of pad hits in addition to the total amount of collected charge. The responses of the detector to electrons and pions were evaluated using a negatively charged secondary beam at 1.0 GeV/c containing 20% electrons at the J-PARC K1.1BR beam line. We observed 7.3 photoelectrons per incident electron. Using the advanced particle identification method, an electron detection efficiency of 83% was achieved with a pion rejection factor of 120. The method improved the pion rejection by approximately a factor of five, compared to the one which just applies a threshold to the amount of collected charge. The newly introduced finely segmented pad readout was found to be effective in rejecting pions.

Investigation on the load-deformation curves of a human healthy heel pad

DEFF Research Database (Denmark)

Fontanella, C. G.; Matteoli, Sara; Carniel, E.L.

2012-01-01

The aims of the present work were to build a 3D subject-specific heel pad model based on the anatomy revealed by MR imaging of a subject's heel pad, and to compare the load–displacement responses obtained from this model with those obtained from a compression device used on the subject's heel pad....... A 30 year-old European healthy female (mass=54kg, height=165cm) was enrolled in this study. Her left foot underwent both MRI and compression tests. A numerical model of the heel region was developed based on a 3D CAD solid model obtained by MR images. The calcaneal fat pad tissue was described...... with a visco-hyperelastic model, while a fiber-reinforced hyperelastic model was formulated for the skin. Numerical analyses were performed to interpret the mechanical response of heel tissues. Different loading conditions were assumed according to experimental tests. The heel tissues showed a non-linear visco...

Development of a hadron blind detector using a finely segmented pad readout

Energy Technology Data Exchange (ETDEWEB)

Kanno, Koki, E-mail: kkanno@post.kek.jp [Department of Physics, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); RIKEN Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Aoki, Kazuya [High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba-shi, Ibaraki 305-0801 (Japan); Aramaki, Yoki; En' yo, Hideto; Kawama, Daisuke [RIKEN Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Komatsu, Yusuke; Masumoto, Shinichi [Department of Physics, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Nakai, Wataru [Department of Physics, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); RIKEN Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Obara, Yuki [Department of Physics, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Ozawa, Kyoichiro; Sekimoto, Michiko [High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba-shi, Ibaraki 305-0801 (Japan); Shibukawa, Takuya [Department of Physics, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Takahashi, Tomonori [Research Center for Nuclear Physics (RCNP), Osaka University, 10-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Watanabe, Yosuke [Department of Physics, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yokkaichi, Satoshi [RIKEN Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

2016-05-21

We constructed a hadron blind detector (HBD) using a finely segmented pad readout. The finely segmented pad readout enabled us to adopt an advanced particle identification method which applies a threshold to the number of pad hits in addition to the total amount of collected charge. The responses of the detector to electrons and pions were evaluated using a negatively charged secondary beam at 1.0 GeV/c containing 20% electrons at the J-PARC K1.1BR beam line. We observed 7.3 photoelectrons per incident electron. Using the advanced particle identification method, an electron detection efficiency of 83% was achieved with a pion rejection factor of 120. The method improved the pion rejection by approximately a factor of five, compared to the one which just applies a threshold to the amount of collected charge. The newly introduced finely segmented pad readout was found to be effective in rejecting pions.

[Response and prognosis of patients with multiple myeloma induced by PAD/TAD].

Science.gov (United States)

Zeng, Tianmei; He, Haiyan; Shi, Haotian; Xi, Hao; Du, Juan; Zhang, Chunyang; Jiang, Hua; Fu, Weijun; Zhou, Fan; Hou, Jian

2015-03-17

To evaluate the impact of cytogenetic grouping and autologous stem cell transplantation on the prognosis of patients with multiple myeloma (MM) induced by PAD (velcade+epirubicin+dexamethasone) and TAD (thalidomide+epirubicin+dexamethasone). A total of 191 patients with a definite diagnosis of MM were enrolled from May 2008 to December 2013 into this prospective study. They were non-randomly induced by PAD (n = 132) or TAD (n = 59) plus autologous stem cell transplantation or chemotherapy. Response and survival rates were also analyzed between two groups. The overall response rates of PAD and TAD groups were 84.4% (108/128) and 69.5% (41/59) (P = 0.011) respectively. The very good partial remission (VGPR) rates were 70.3% (90/128) and 32.2% (19/59) (P TAD. After PAD induction, cytogenetic grouping may further distinguish the prognosis of MM patients. For FISH high-risk patients, their PFS is prolonged by autologous stem cell transplantation.

Is the iPad suitable for image display at American Board of Radiology examinations?

Science.gov (United States)

Toomey, Rachel J; Rainford, Louise A; Leong, David L; Butler, Marie-Louise; Evanoff, Michael G; Kavanagh, Eoin C; Ryan, John T

2014-11-01

The study aimed to determine the acceptability of the iPad 3 as a display option for American Board of Radiology (ABR) examinations. A set of 20 cases for each of nine specialties examined by the ABR was prepared. Each comprised between one and seven images and case information and had been used in previous ABR Initial Certification examinations. Examining radiologists (n = 119) at the ABR oral Initial Certification examinations reviewed sets from one or more specialties on both a 2 MP LED monitor and on the iPad 3 and rated the visibility of the salient image features for each case. The Wilcoxon signed rank test was performed to compare ratings. In addition, a thematic analysis of participants' opinions was undertaken. When all specialties were pooled, the iPad 3 ratings were significantly higher than the monitor ratings (p = 0.0217). The breast, gastrointestinal, genitourinary, and nuclear medicine specialties also returned significantly higher ratings for the visibility of relevant image features for the iPad 3. Monitor ratings were significantly higher for the vascular and interventional specialty, although no images were rated unacceptably poor on the iPad in this specialty. The relevant image features were rated more visible on the iPad 3 than on the monitors overall. The iPad 3 was well accepted by a large majority of examiners and can be considered adequate for image display for examination in most or all specialties.

Expectations of iPad use in an internal medicine residency program: is it worth the "hype"?

Science.gov (United States)

Luo, Nancy; Chapman, Christopher G; Patel, Bhakti K; Woodruff, James N; Arora, Vineet M

2013-05-08

While early reports highlight the benefits of tablet computing in hospitals, introducing any new technology can result in inflated expectations. The aim of the study is to compare anticipated expectations of Apple iPad use and perceptions after deployment among residents. 115 internal medicine residents received Apple iPads in October 2010. Residents completed matched surveys on anticipated usage and perceptions after distribution 1 month prior and 4 months after deployment. In total, 99% (114/115) of residents responded. Prior to deployment, most residents believed that the iPad would improve patient care and efficiency on the wards; however, fewer residents "strongly agreed" after deployment (34% vs 15% for patient care, PApple iOS product owners were also more likely to use the iPad in key areas. Overall, 84% of residents thought the iPad was a good investment for the residency program, and over half of residents (58%) reported that patients commented on the iPad in a positive way. While the use of tablets such as the iPad by residents is generally well received, high initial expectations highlight the danger of implementing new technologies. Education on the realistic expectations of iPad benefits may be warranted.

Ectopic expression of AtPAD4 broadens resistance of soybean to soybean cyst and root-knot nematodes.

Science.gov (United States)

Youssef, Reham M; MacDonald, Margaret H; Brewer, Eric P; Bauchan, Gary R; Kim, Kyung-Hwan; Matthews, Benjamin F

2013-04-25

The gene encoding PAD4 (PHYTOALEXIN-DEFICIENT4) is required in Arabidopsis for expression of several genes involved in the defense response to Pseudomonas syringae pv. maculicola. AtPAD4 (Arabidopsis thaliana PAD4) encodes a lipase-like protein that plays a regulatory role mediating salicylic acid signaling. We expressed the gene encoding AtPAD4 in soybean roots of composite plants to test the ability of AtPAD4 to deter plant parasitic nematode development. The transformed roots were challenged with two different plant parasitic nematode genera represented by soybean cyst nematode (SCN; Heterodera glycines) and root-knot nematode (RKN; Meloidogyne incognita). Expression of AtPAD4 in soybean roots decreased the number of mature SCN females 35 days after inoculation by 68 percent. Similarly, soybean roots expressing AtPAD4 exhibited 77 percent fewer galls when challenged with RKN. Our experiments show that AtPAD4 can be used in an economically important crop, soybean, to provide a measure of resistance to two different genera of nematodes.

Analisis Penerimaan PAD Pada Dinas Perikanan dan Peternakan Kabupaten Tebo

Directory of Open Access Journals (Sweden)

Eko Purnarianto

2016-06-01

Full Text Available Abstract. This study aims to analyze potential, efficiency, effectivity and contribution of PAD admission at Department of Fishery and Animal Husbandry in Tebo Regencyincluding the strategy establishment to increase its revenue.The analysis used is a potential formula, efficiency ratio, effectivity ratio, contributions ratio and SWOT analysis.The results shows that the potential revenue of retribution slaughterhouse (RPH, the potential sales of livestock, and potential sales fishery product are beyond the current target. The efficiency level of retribution slaughterhouse (RPH and sales of fishery product is poor, but the sales of livestock is very efficient. Effectivity level of livestock and fishery product sales are low, whileretribution slaughterhouses(RPH is not effective regarded to its potential  but in the contrary for its target. Contribution of PAD admission of Fishery and Animal Husbandry Department is very low regarded Tebo Regency PAD. The result of SWOT analysis of retribution slaughter house (RPH admission using WO (Weakness-Opportunity strategy, livestock sales using SO (Strength-Oppurtunity strategy, and fishery product sales using ST (strength-threat strategy. Keywords: Retribution SlaughterHouse (RPH, Sales of Fishery, Livestock Sales, SWOT Analysis   Abstrak. Penelitian ini bertujuan untuk menganalisis potensi, efisiensi, efektivitas dan kontribusi penerimaan PAD pada Dinas Perikanan dan Peternakan Kabupaten Teboserta menetapkan strategi untuk peningkatan penerimaan PAD. Analisis yang digunakan adalah rumus potensi, rasio efisiensi, rasio efektivitas, rasio kontribusi dan analisis SWOT.Hasil penelitian menunjukkan bahwa potensi penerimaan retribusi rumah potong hewan (RPH, potensi penjualan hasil peternakan, potensi  penjualan hasil perikanan lebih besar dari target yang telah ditetapkan. Tingkat efisiensi retribusi RPH dan penjualan hasil perikanan tidak efisien, penjualan hasil peternakan sangat efisien. Tingkat

iPad: Semantic annotation and markup of radiological images.

Science.gov (United States)

Rubin, Daniel L; Rodriguez, Cesar; Shah, Priyanka; Beaulieu, Chris

2008-11-06

Radiological images contain a wealth of information,such as anatomy and pathology, which is often not explicit and computationally accessible. Information schemes are being developed to describe the semantic content of images, but such schemes can be unwieldy to operationalize because there are few tools to enable users to capture structured information easily as part of the routine research workflow. We have created iPad, an open source tool enabling researchers and clinicians to create semantic annotations on radiological images. iPad hides the complexity of the underlying image annotation information model from users, permitting them to describe images and image regions using a graphical interface that maps their descriptions to structured ontologies semi-automatically. Image annotations are saved in a variety of formats,enabling interoperability among medical records systems, image archives in hospitals, and the Semantic Web. Tools such as iPad can help reduce the burden of collecting structured information from images, and it could ultimately enable researchers and physicians to exploit images on a very large scale and glean the biological and physiological significance of image content.

New Encryption Scheme of One-Time Pad Based on KDC

Science.gov (United States)

Xie, Xin; Chen, Honglei; Wu, Ying; Zhang, Heng; Wu, Peng

As more and more leakage incidents come up, traditional encryption system has not adapted to the complex and volatile network environment, so, there should be a new encryption system that can protect information security very well, this is the starting point of this paper. Based on DES and RSA encryption system, this paper proposes a new scheme of one time pad, which really achieves "One-time pad" and provides information security a new and more reliable encryption method.

iPad-presented social stories for young children with autism.

Science.gov (United States)

Vandermeer, Julianne; Beamish, Wendi; Milford, Todd; Lang, Wayne

2015-04-01

This study investigated the effectiveness of iPad-presented social stories in increasing the on-task behaviour of three young children with autism. A single-subject with multiple baseline across participants design was employed with three 4-year-old children to assess intervention effectiveness during structured table top activities. Observational data were digitally recorded, scored, graphed, and interpreted using 10-second interval measures over 5-min periods across baseline, intervention, and withdrawal phases. The combination of the social story together with the iPad proved to be an effective intervention for one of the three child participants. These findings confirm that the intervention may be effective with some children, but not others. Overall, this study builds on existing research that supports social stories as a promising practice. Further research into the use of iPad-presented social stories, particularly for children of varying ages, abilities, and learning styles is recommended.

Reversible adhesion switching of porous fibrillar adhesive pads by humidity.

Science.gov (United States)

Xue, Longjian; Kovalev, Alexander; Dening, Kirstin; Eichler-Volf, Anna; Eickmeier, Henning; Haase, Markus; Enke, Dirk; Steinhart, Martin; Gorb, Stanislav N

2013-01-01

We report reversible adhesion switching on porous fibrillar polystyrene-block-poly(2-vinyl pyridine) (PS-b-P2VP) adhesive pads by humidity changes. Adhesion at a relative humidity of 90% was more than nine times higher than at a relative humidity of 2%. On nonporous fibrillar adhesive pads of the same material, adhesion increased only by a factor of ~3.3. The switching performance remained unchanged in at least 10 successive high/low humidity cycles. Main origin of enhanced adhesion at high humidity is the humidity-induced decrease in the elastic modulus of the polar component P2VP rather than capillary force. The presence of spongelike continuous internal pore systems with walls consisting of P2VP significantly leveraged this effect. Fibrillar adhesive pads on which adhesion is switchable by humidity changes may be used for preconcentration of airborne particulates, pollutants, and germs combined with triggered surface cleaning.

Internal strain estimation for quantification of human heel pad elastic modulus: A phantom study.

Science.gov (United States)

Holst, Karen; Liebgott, Hervé; Wilhjelm, Jens E; Nikolov, Svetoslav; Torp-Pedersen, Søren T; Delachartre, Philippe; Jensen, Jørgen A

2013-02-01

Shock absorption is the most important function of the human heel pad. However, changes in heel pad elasticity, as seen in e.g. long-distance runners, diabetes patients, and victims of Falanga torture are affecting this function, often in a painful manner. Assessment of heel pad elasticity is usually based on one or a few strain measurements obtained by an external load-deformation system. The aim of this study was to develop a technique for quantitative measurements of heel pad elastic modulus based on several internal strain measures from within the heel pad by use of ultrasound images. Nine heel phantoms were manufactured featuring a combination of three heel pad stiffnesses and three heel pad thicknesses to model the normal human variation. Each phantom was tested in an indentation system comprising a 7MHz linear array ultrasound transducer, working as the indentor, and a connected load cell. Load-compression data and ultrasound B-mode images were simultaneously acquired in 19 compression steps of 0.1mm each. The internal tissue displacement was for each step calculated by a phase-based cross-correlation technique and internal strain maps were derived from these displacement maps. Elastic moduli were found from the resulting stress-strain curves. The elastic moduli made it possible to distinguish eight of nine phantoms from each other according to the manufactured stiffness and showed very little dependence of the thickness. Mean elastic moduli for the three soft, the three medium, and the three hard phantoms were 89kPa, 153kPa, and 168kPa, respectively. The combination of ultrasound images and force measurements provided an effective way of assessing the elastic properties of the heel pad due to the internal strain estimation. Copyright © 2012 Elsevier B.V. All rights reserved.

Dietary regimens of athletes competing at the Delhi 2010 Commonwealth Games.

Science.gov (United States)

Pelly, Fiona E; Burkhart, Sarah J

2014-02-01

The aim of this study was to investigate the dietary regimens reported by athletes competing at a major international competition and report whether these were based on nutrient composition, religious beliefs, cultural eating style, food intolerance or avoidance of certain ingredients. A questionnaire was randomly distributed to 351 athletes in the main dining hall of the athletes' village over the three main meal periods during the Delhi 2010 Commonwealth Games (23rd Sept-14th Oct, 2010). The majority (n = 218, 62%) of athletes reported following one or more dietary regimens, with 50% (n = 174) following a diet based on the nutrient composition of the food. Significantly more athletes from weight category and aesthetic sports (28%, p = .005) and from power/sprint sports (41%, p = .004) followed low fat and high protein regimens respectively. Other specialized dietary regimens were followed by 33% of participants, with avoidance of red meat (13%), vegetarian (7%), Halal (6%), and low lactose regimens (5%) reported most frequently. Significantly more athletes from non-Western regions followed a vegetarian diet (p food items are available at similar events.

Padé approximations and diophantine geometry.

Science.gov (United States)

Chudnovsky, D V; Chudnovsky, G V

1985-04-01

Using methods of Padé approximations we prove a converse to Eisenstein's theorem on the boundedness of denominators of coefficients in the expansion of an algebraic function, for classes of functions, parametrized by meromorphic functions. This result is applied to the Tate conjecture on the effective description of isogenies for elliptic curves.

A fast integrated readout system for a cathode pad photon detector

Energy Technology Data Exchange (ETDEWEB)

French, M. (Rutherford Appleton Lab., Chilton (United Kingdom)); Lovell, M. (Rutherford Appleton Lab., Chilton (United Kingdom)); Chesi, E. (CERN, ECP Div., Geneva (Switzerland)); Racz, A. (CERN, ECP Div., Geneva (Switzerland)); Seguinot, J. (Coll. de France, Paris (France)); Ypsilantis, T. (Coll. de France, Paris (France)); Arnold, R. (CRN, Louis Pasteur Univ., Strasbourg (France)); Guyonnet, J.L. (CRN, Louis Pasteur Univ., Strasbourg (France)); Egger, J. (Paul Scherrer Inst., Villigen (Switzerland)); Gabathuler, K. (Paul Scherrer Inst., Villigen (Switzerland))

1994-04-01

A fast integrated electronic chain is presented to read out the cathode pad array of a multiwire photon detector for a fast RICH counter. Two VLSI circuits have been designed and produced. An analog eight channel, low noise, fast, bipolar, current preamplifier and discriminator chip serves as front-end electronics. It has an rms equivalent noise current of 10 nA (2000 e[sup -]), 50 MHz bandwidth with 10 mW of power consumption per channel. Two analogue chips are coupled to a digital 16 channels CMOS readout chip, operating at 20 MHz, that provides a pipelined delay of 1.3 [mu]s and zero suppression with a power consumption of about 6 mW per channel. Readout of a 4000 pad sector requires 3-4 [mu]s depending on the number of hit pads. The full RICH counter is made up of many of such sectors (the prototype has three fully equipped sectors), read out in parallel. The minimum time to separate successive hits on the same pad is about 70 ns. The time skew of the full chain is about 15 ns. (orig.)

Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

Science.gov (United States)

Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

2014-09-01

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence

How does the canine paw pad attenuate ground impacts? A multi-layer cushion system

Directory of Open Access Journals (Sweden)

Huaibin Miao

2017-12-01

Full Text Available Macroscopic mechanical properties of digitigrade paw pads, such as non-linear elastic and variable stiffness, have been investigated in previous studies; however, little is known about the micro-scale structural characteristics of digitigrade paw pads, or the relationship between these characteristics and the exceptional cushioning of the pads. The digitigrade paw pad consists of a multi-layered structure, which is mainly comprised of a stratified epithelium layer, a dermis layer and a subcutaneous layer. The stratified epithelium layer and dermal papillae constitute the epidermis layer. Finite element analyses were carried out and showed that the epidermis layer effectively attenuated the ground impact across impact velocities of 0.05–0.4 m/s, and that the von Mises stresses were uniformly distributed in this layer. The dermis layer encompassing the subcutaneous layer can be viewed as a hydrostatic system, which can store, release and dissipate impact energy. All three layers in the paw pad work as a whole to meet the biomechanical requirements of animal locomotion. These findings provide insights into the biomechanical functioning of digitigrade paw pads and could be used to facilitate bio-inspired, ground-contacting component development for robots and machines, as well as contribute to footwear design.

How does the canine paw pad attenuate ground impacts? A multi-layer cushion system.

Science.gov (United States)

Miao, Huaibin; Fu, Jun; Qian, Zhihui; Ren, Luquan; Ren, Lei

2017-12-15

Macroscopic mechanical properties of digitigrade paw pads, such as non-linear elastic and variable stiffness, have been investigated in previous studies; however, little is known about the micro-scale structural characteristics of digitigrade paw pads, or the relationship between these characteristics and the exceptional cushioning of the pads. The digitigrade paw pad consists of a multi-layered structure, which is mainly comprised of a stratified epithelium layer, a dermis layer and a subcutaneous layer. The stratified epithelium layer and dermal papillae constitute the epidermis layer. Finite element analyses were carried out and showed that the epidermis layer effectively attenuated the ground impact across impact velocities of 0.05-0.4 m/s, and that the von Mises stresses were uniformly distributed in this layer. The dermis layer encompassing the subcutaneous layer can be viewed as a hydrostatic system, which can store, release and dissipate impact energy. All three layers in the paw pad work as a whole to meet the biomechanical requirements of animal locomotion. These findings provide insights into the biomechanical functioning of digitigrade paw pads and could be used to facilitate bio-inspired, ground-contacting component development for robots and machines, as well as contribute to footwear design. © 2017. Published by The Company of Biologists Ltd.

The Sex Res Non Naturales and the Regimen of Health

DEFF Research Database (Denmark)

Agerholm, Frank Juul

The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle......The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle...

Relationship between person's health beliefs and diabetes self-care management regimen.

Science.gov (United States)

Albargawi, Moudi; Snethen, Julia; Al Gannass, Abdulaziz; Kelber, Sheryl

2017-12-01

To examine the relationship between the health beliefs of Saudi adults with type 2 diabetes mellitus (T2DM) and their adherence to daily diabetes self-care management regimen. A secondary aim was to examine the health beliefs of adults with a diabetic foot ulcer (DFU) and participants without a DFU. Descriptive correlational design with a convenience sample of 30 participants. Participants were recruited for this pilot study from an outpatient clinic at King Abdulaziz Medical City in Riyadh. The participants completed self-reported questionnaires about their health beliefs, daily diabetes self-care management regimen, and demographic characteristics. Hierarchical multiple regression analysis was used to test the interaction effects. Participants who reported having a high internal health locus of control (IHLoC) and a high level of self-efficacy (SE) adhered well to their foot care regimen (P = .038). The more the participants believed that God controls their health, and the higher their SE, the greater the participant's adherence to their medication regimen (P = .035). The stronger the participant's belief that following their diabetes treatment regimen will lead to good outcomes, the greater the participant's adherence to their dietary regimen for those with a low IHLoC (P = .015). Participants with a high SE and reported that their doctor is able to help them control their diabetes were more likely to follow their dietary regimen (P = .048). Participants with a DFU reported having additional health conditions besides T2DM (P = .018) and had less than a college education (P = .015). Although participants with a DFU reported that they were responsible for their diabetes (P = .21), they stated that God manages their diabetes (P = .29), and the disease can be controlled based on luck (P = .10). Participants' beliefs were found to influence their daily self-care management regimen. Further studies are needed using a larger sample. Copyright © 2017

iTE: Student Teachers Using iPad on a Second Level Initial Teacher Education Programme

Science.gov (United States)

Mac Mahon, Brendan; Grádaigh, Seán Ó.; Ghuidhir, Sinéad Ní

2016-01-01

Research on the use of iPad in initial teacher education is limited. This paper outlines a study to examine how the professional learning and pedagogical knowledge development of student teachers could be supported following 1:1 iPad deployment on a second-level initial teacher education programme in Ireland. Findings show that iPad can be…

Comparison of Models for the Steady-State Analysis of Tilting-Pad Thrust Bearings

DEFF Research Database (Denmark)

Heinrichson, Niels; Santos, Ilmar

2005-01-01

Prediction of the minimum oil film thickness and the maximum temperature on the surface of the bearing pad is crucial in the design and dimensioning of bearings. Friction loss, oil bath temperature and pad deflection are other parameters of interest. Depending on the desired information a numerical...... for the groove between pads and the oil bath temperature from energy equilibrium for the entire bearing. The main theoretical contribution of this paper is the elaboration and comparison of 7 different mathematical models of increasing complexity. The results are compared to experimental data for steady......-state operation of a 228 mm outer diameter bearing. It is found that for the given bearing a two dimensional model is sufficient to estimate the minimum oil film thickness and the maximum temperature on the pad surface. Three dimensional modelling does not improve the quality of the results....

Water Quality Survey of Splash Pads After A Waterborne Salmonellosis Outbreak--Tennessee, 2014.

Science.gov (United States)

Clayton, Joshua L; Manners, Judy; Miller, Susan; Shepherd, Craig; Dunn, John R; Schaffner, William; Jones, Timothy F

2017-06-01

Waterborne outbreaks of salmonellosis are uncommon. The Tennessee Department of Health investigated a salmonellosis outbreak of 10 cases with the only common risk factor being exposure to a single splash pad. Risks included water splashed in the face at the splash pad and no free residual chlorine in the water system. We surveyed water quality and patron behaviors at splash pads statewide. Of the 29 splash pads participating in the water quality survey, 24 (83%) used a recirculating water system. Of the 24, 5 (21%) water samples were tested by polymerase chain reaction and found to be positive for E. coli, Giardia, norovirus, or Salmonella. Among 95 patrons observed, we identified common high-risk behaviors of sitting on the fountain or spray head and putting mouth to water. Water venue regulations and improved education of patrons are important to aid prevention efforts.

Introduction to PAC/PAD

International Nuclear Information System (INIS)

Mahnke, H.E.

1988-01-01

Both methods, Perturbed Angular Correlation (PAC) utilizing radioactive probes and Perturbed Angular Distribution (PAD) following nuclear reactions measure hyperfine interaction parameters and allow to study magnetism on a rather local scale. While both techniques are based on the same theory the underlying concepts are quite different. Examples on local moments, influence of the nearest-neighbor to the magnetic field in ferromagnets, knight shift in nonmagnetic materials, and magnetism in high-temperature superconductors and related oxides illustrate the recent developments within the methods and the improvements in their sensitivity and resolution. (orig.)

An efficient 2D 11B–11B solid-state NMR spectroscopy strategy for monitoring covalent self-assembly of boronic acid-derived compounds: the transformation and unique architecture of bortezomib molecules in the solid state

Czech Academy of Sciences Publication Activity Database

Brus, Jiří; Czernek, Jiří; Urbanová, Martina; Kobera, Libor; Jegorov, A.

2017-01-01

Roč. 19, č. 1 (2017), s. 487-495 ISSN 1463-9076 R&D Projects: GA ČR(CZ) GA14-03636S; GA ČR(CZ) GA16-04109S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : NMR crystalography * bortezomib * solid-state self-assembly Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.123, year: 2016

Exploring integral controllers in actively-lubricated tilting-pad journal bearings

DEFF Research Database (Denmark)

Salazar, Jorge Andrés González; Santos, Ilmar

2015-01-01

investigation of integral controllers for feedback-controlled lubrication with the aim of: a) presetting the static journal center and consequently exploring the changes of bearing dynamic properties; b) obtaining an integral controller capable of re-positioning the static journal eccentricity for matching......Active tilting-pad journal bearings with radial oil injection combine good stability properties of conventional tilting-pad journal bearings with the capability of improving their dynamic properties even more by control techniques. The main contribution of this work is the experimental...

Development of a high resolution plantar pressure monitoring pad based on fiber Bragg grating (FBG) sensors.

Science.gov (United States)

Suresh, R; Bhalla, S; Hao, J; Singh, C

2015-01-01

High importance is given to plantar pressure monitoring in the field of biomedical engineering for the diagnosis of posture related ailments associated with diseases such as diabetes and gonarthrosis. This paper presents the proof-of-concept development of a new high resolution plantar pressure monitoring pad based on fiber Bragg grating (FBG) sensors. In the proposed configuration, the FBG sensors are embedded within layers of carbon composite material (CCM) in turn conforming to an arc shape. A total of four such arc shaped sensors are instrumented in the pad at the locations of the forefoot and the hind foot. As a test of the pad, static plantar pressure is monitored on normal subjects under various posture conditions. The pad is evaluated both as a standalone platform as well as a pad inserted inside a standard shoe. An average pressure sensitivity of 1.2 pm/kPa and a resolution of approximately 0.8 kPa is obtained in this special configuration. The pad is found to be suitable in both configurations- stand-alone pad as well as an insert inside a standard shoe. The proposed set up offers a cost-effective high resolution and accurate plantar pressure measurement system suitable for clinical deployment. The novelty of the developed pressure pad lies in its ability to be used both as platform type as well as inserted in-sole type sensor system.

Plasma cell leukemia

DEFF Research Database (Denmark)

Fernández de Larrea, C; Kyle, R A; Durie, B G M

2013-01-01

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic......-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10(9)/l) of plasma cells in the peripheral blood. It is proposed that the thresholds...... regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding...

Crystal structures of two transcriptional regulators from Bacillus cereus define the conserved structural features of a PadR subfamily.

Directory of Open Access Journals (Sweden)

Guntur Fibriansah

Full Text Available PadR-like transcriptional regulators form a structurally-related family of proteins that control the expression of genes associated with detoxification, virulence and multi-drug resistance in bacteria. Only a few members of this family have been studied by genetic, biochemical and biophysical methods, and their structure/function relationships are still largely undefined. Here, we report the crystal structures of two PadR-like proteins from Bacillus cereus, which we named bcPadR1 and bcPadR2 (products of gene loci BC4206 and BCE3449 in strains ATCC 14579 and ATCC 10987, respectively. BC4206, together with its neighboring gene BC4207, was previously shown to become significantly upregulated in presence of the bacteriocin AS-48. DNA mobility shift assays reveal that bcPadR1 binds to a 250 bp intergenic region containing the putative BC4206-BC4207 promoter sequence, while in-situ expression of bcPadR1 decreases bacteriocin tolerance, together suggesting a role for bcPadR1 as repressor of BC4206-BC4207 transcription. The function of bcPadR2 (48% identical in sequence to bcPadR1 is unknown, but the location of its gene just upstream from genes encoding a putative antibiotic ABC efflux pump, suggests a role in regulating antibiotic resistance. The bcPadR proteins are structurally similar to LmrR, a PadR-like transcription regulator in Lactococcus lactis that controls expression of a multidrug ABC transporter via a mechanism of multidrug binding and induction. Together these proteins define a subfamily of conserved, relatively small PadR proteins characterized by a single C-terminal helix for dimerization. Unlike LmrR, bcPadR1 and bcPadR2 lack a central pore for ligand binding, making it unclear whether the transcriptional regulatory roles of bcPadR1 and bcPadR2 involve direct ligand recognition and induction.

On the simplifications for the thermal modeling of tilting-pad journal bearings under thermoelastohydrodynamic regime

DEFF Research Database (Denmark)

Cerda Varela, Alejandro Javier; Fillon, Michel; Santos, Ilmar

2012-01-01

formulation for inclusion of the heat transfer effects between oil film and pad surface. Such simplified approach becomes necessary when modeling the behavior of tilting-pad journal bearings operating on controllable lubrication regime. Three different simplified heat transfer models are tested, by comparing...... are strongly dependent on the Reynolds number for the oil flow in the bearing. For bearings operating in laminar regime, the decoupling of the oil film energy equation solving procedure, with no heat transfer terms included, with the pad heat conduction problem, where the oil film temperature is applied......The relevance of calculating accurately the oil film temperature build up when modeling tilting-pad journal bearings is well established within the literature on the subject. This work studies the feasibility of using a thermal model for the tilting-pad journal bearing which includes a simplified...

Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study.

Directory of Open Access Journals (Sweden)

Jennifer Vandooren

Full Text Available Gelatinase B or matrix metalloproteinase-9 (MMP-9 (EC 3.4.24.35 is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM, the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2 activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations.

Engaging Primary School Students in Mathematics: Can iPads Make a Difference?

Science.gov (United States)

Hilton, Annette

2018-01-01

Research on the impact of the integration of technologies such as iPads on primary students' attitudes and engagement in mathematics is limited. Further, there have been claims that teachers' pedagogical choices can strongly influence the effectiveness of iPads for engaging students in mathematics. This paper presents an investigation of the…

Establishment of Approximate Analytical Model of Oil Film Force for Finite Length Tilting Pad Journal Bearings

Directory of Open Access Journals (Sweden)

Yongliang Wang

2015-01-01

Full Text Available Tilting pad bearings offer unique dynamic stability enabling successful deployment of high-speed rotating machinery. The model of dynamic stiffness, damping, and added mass coefficients is often used for rotordynamic analyses, and this method does not suffice to describe the dynamic behaviour due to the nonlinear effects of oil film force under larger shaft vibration or vertical rotor conditions. The objective of this paper is to present a nonlinear oil force model for finite length tilting pad journal bearings. An approximate analytic oil film force model was established by analysing the dynamic characteristic of oil film of a single pad journal bearing using variable separation method under the dynamic π oil film boundary condition. And an oil film force model of a four-tilting-pad journal bearing was established by using the pad assembly technique and considering pad tilting angle. The validity of the model established was proved by analyzing the distribution of oil film pressure and the locus of journal centre for tilting pad journal bearings and by comparing the model established in this paper with the model established using finite difference method.

Foam pad of appropriate thickness can improve diagnostic value of foam posturography in detecting postural instability.

Science.gov (United States)

Liu, Bo; Leng, Yangming; Zhou, Renhong; Liu, Jingjing; Liu, Dongdong; Liu, Jia; Zhang, Su-Lin; Kong, Wei-Jia

2018-04-01

The present study investigated the effect of foam thickness on postural stability in patients with unilateral vestibular hypofunction (UVH) during foam posturography. Static and foam posturography were performed in 33 patients (UVH group) and 30 healthy subjects (control group) with eyes open (EO) and closed (EC) on firm surface and on 1-5 foam pad(s). Sway velocity (SV) of center of pressure, standing time before falling (STBF) and falls reaction were recorded and analyzed. (1) SVs had an increasing tendency in both groups as the foam pads were added under EO and EC conditions. (2) STBFs, only in UVH group with EC, decreased with foam thickness increasing. (3) Significant differences in SV were found between the control and UVH group with EO (except for standing on firm surface, on 1 and 2 foam pad(s)) and with EC (all surface conditions). (4) Receiver operating characteristic curve analysis showed that the SV could better reflect the difference in postural stability between the two groups while standing on the 4 foam pads with EC. Our study showed that diagnostic value of foam posturography in detecting postural instability might be enhanced by using foam pad of right thickness.

Cask crush pad analysis using detailed and simplified analysis methods

International Nuclear Information System (INIS)

Uldrich, E.D.; Hawkes, B.D.

1997-01-01

A crush pad has been designed and analyzed to absorb the kinetic energy of a hypothetically dropped spent nuclear fuel shipping cask into a 44-ft. deep cask unloading pool at the Fluorinel and Storage Facility (FAST). This facility, located at the Idaho Chemical Processing Plant (ICPP) at the Idaho national Engineering and Environmental Laboratory (INEEL), is a US Department of Energy site. The basis for this study is an analysis by Uldrich and Hawkes. The purpose of this analysis was to evaluate various hypothetical cask drop orientations to ensure that the crush pad design was adequate and the cask deceleration at impact was less than 100 g. It is demonstrated herein that a large spent fuel shipping cask, when dropped onto a foam crush pad, can be analyzed by either hand methods or by sophisticated dynamic finite element analysis using computer codes such as ABAQUS. Results from the two methods are compared to evaluate accuracy of the simplified hand analysis approach

Launch Pad Escape System Design (Human Spaceflight)

Science.gov (United States)

Maloney, Kelli

2011-01-01

A launch pad escape system for human spaceflight is one of those things that everyone hopes they will never need but is critical for every manned space program. Since men were first put into space in the early 1960s, the need for such an Emergency Escape System (EES) has become apparent. The National Aeronautics and Space Administration (NASA) has made use of various types of these EESs over the past 50 years. Early programs, like Mercury and Gemini, did not have an official launch pad escape system. Rather, they relied on a Launch Escape System (LES) of a separate solid rocket motor attached to the manned capsule that could pull the astronauts to safety in the event of an emergency. This could only occur after hatch closure at the launch pad or during the first stage of flight. A version of a LES, now called a Launch Abort System (LAS) is still used today for all manned capsule type launch vehicles. However, this system is very limited in that it can only be used after hatch closure and it is for flight crew only. In addition, the forces necessary for the LES/LAS to get the capsule away from a rocket during the first stage of flight are quite high and can cause injury to the crew. These shortcomings led to the development of a ground based EES for the flight crew and ground support personnel as well. This way, a much less dangerous mode of egress is available for any flight or ground personnel up to a few seconds before launch. The early EESs were fairly simple, gravity-powered systems to use when thing's go bad. And things can go bad very quickly and catastrophically when dealing with a flight vehicle fueled with millions of pounds of hazardous propellant. With this in mind, early EES designers saw such a passive/unpowered system as a must for last minute escapes. This and other design requirements had to be derived for an EES, and this section will take a look at the safety design requirements had to be derived for an EES, and this section will take a look at

Hand hygiene regimens for the reduction of risk in food service environments.

Science.gov (United States)

Edmonds, Sarah L; McCormack, Robert R; Zhou, Sifang Steve; Macinga, David R; Fricker, Christopher M

2012-07-01

Pathogenic strains of Escherichia coli and human norovirus are the main etiologic agents of foodborne illness resulting from inadequate hand hygiene practices by food service workers. This study was conducted to evaluate the antibacterial and antiviral efficacy of various hand hygiene product regimens under different soil conditions representative of those in food service settings and assess the impact of product formulation on this efficacy. On hands contaminated with chicken broth containing E. coli, representing a moderate soil load, a regimen combining an antimicrobial hand washing product with a 70% ethanol advanced formula (EtOH AF) gel achieved a 5.22-log reduction, whereas a nonantimicrobial hand washing product alone achieved a 3.10log reduction. When hands were heavily soiled from handling ground beef containing E. coli, a wash-sanitize regimen with a 0.5% chloroxylenol antimicrobial hand washing product and the 70% EtOH AF gel achieved a 4.60-log reduction, whereas a wash-sanitize regimen with a 62% EtOH foam achieved a 4.11-log reduction. Sanitizing with the 70% EtOH AF gel alone was more effective than hand washing with a nonantimicrobial product for reducing murine norovirus (MNV), a surrogate for human norovirus, with 2.60- and 1.79-log reductions, respectively. When combined with hand washing, the 70% EtOH AF gel produced a 3.19-log reduction against MNV. A regimen using the SaniTwice protocol with the 70% EtOH AF gel produced a 4.04-log reduction against MNV. These data suggest that although the process of hand washing helped to remove pathogens from the hands, use of a wash-sanitize regimen was even more effective for reducing organisms. Use of a high-efficacy sanitizer as part of a wash-sanitize regimen further increased the efficacy of the regimen. The use of a well-formulated alcohol-based hand rub as part of a wash-sanitize regimen should be considered as a means to reduce risk of infection transmission in food service facilities.

The iPad: tablet technology to support nursing and midwifery student learning: an evaluation in practice.

Science.gov (United States)

Brown, Janie; McCrorie, Pamela

2015-03-01

This research explored the impact of tablet technology, in the form of Apple iPads, on undergraduate nursing and midwifery students' learning outcomes. In simulated clinical learning environments, first-year nursing students (n = 30) accessed apps and reference materials on iPads. Third-year nursing students (n = 88) referred to clinical guidelines to aid their decision making when problem solving. First-year midwifery students (n = 25) filmed themselves undertaking a skill and then immediately played back the video file. A total of 45 students completed an online questionnaire that allowed for qualitative comments. Students reported finding the use of iPads easy and that iPads provided point-of-care access to resources, ensuring an evidence-based approach to clinical decision making. iPads reportedly improved student efficiency and time management, while improving their ability to provide patient education. Students who used iPads for the purpose of formative self-assessment appreciated the immediate feedback and opportunity to develop clinical skills.

Menstrual pad, a cervical cancer screening tool, a population-based study in rural India.

Science.gov (United States)

Budukh, Atul; Palayekar, Vrushali; Maheshwari, Amita; Deodhar, Kedar; Purwar, Pallavi; Bagal, Sonali; Vadigoppula, Ashok; Lokhande, Manoj; Panse, Nandkumar; Dikshit, Rajesh; Badwe, Rajendra

2017-07-12

In the rural areas of India, women generally use a piece of old cloth as a menstrual device. The aim of this study was to detect human papilloma virus (HPV) from menstrual blood on the menstrual pad and assess whether this could be a useful screening tool for cervical cancer. In Jamkhed area of rural Maharashtra, (population A), we collected menstrual pads from women who provided consent in the 30-50 year age group. The women who had provided menstrual pads underwent HC2 testing. We standardized the method for extracting DNA by PCR from the menstrual pad. The women who tested HPV positive, on the basis of HC2/PCR testing, underwent colposcopy. In the rural population of Pune area of Maharashtra state (population B), menstrual pads were collected. HPV was tested using the PCR method. HPV-positive women and a few HPV-negative women, selected randomly, underwent colposcopy and HC2 testing. In population A, 164 women provided their used menstrual pads and also underwent an HC2 screening test. Of these, six (3.2%) cases were reported as HPV positive. In population B, 365 women provided their used menstrual pads for HPV testing, of which 18 (4.9%) cases were diagnosed as HPV positive. The women who tested HPV positive, on the basis of PCR testing, and 10% randomly selected HPV-negative cases (37) and 18 women who voluntary requested testing underwent colposcopy and HC2 testing. The sensitivity of menstrual pad HPV testing compared with gold standard HC2 testing was 83% [95% confidence interval (CI): 0.47-0.97], 67% (95% CI: 0.30-0.91) and specificity was 99% (95% CI: 0.96-0.99), 88% (95% CI: 0.77-0.94) in population A and population B, respectively. The sensitivity of diagnosing CIN lesion was 83% (95% CI: 0.44-0.97) and specificity was 95% (95% CI: 0.91-0.97). On the basis of the sensitivity and specificity results, and the completely noninvasive, simple and convenient method of detecting HPV, menstrual pad might be considered a cervical cancer screening tool in rural

Eruptive furunculosis following the soak and smear regimen.

Science.gov (United States)

Martires, Kathryn; Sukhdeo, Kumar; Meinhardt, Eric

2015-02-18

The 'soak and smear' regimen is a highly effective method for localised topical therapy employed by dermatologists for widespread inflammatory skin conditions. The regimen involves application of topical medication under occlusion after soaking in water. Complications from this treatment method are rare. We present a case of multiple, generalised methicillin-resistant Staphylococcus aureus (MRSA)-positive furuncles arising in a patient as an unexpected consequence of therapy. The case highlights an unanticipated risk of a commonly employed treatment amid an epidemic of MRSA in the community. 2015 BMJ Publishing Group Ltd.

Solar panel assembly and support pad

Energy Technology Data Exchange (ETDEWEB)

Hawley, W.W.

1980-10-07

A solar panel assembly is described comprising at least one solar panel, support means for carrying said panel, and at least one support pad having a base plate, upstanding longitudinal sides, and spaced apart flange means for connection to said support means, said upstanding sides and opposed flange means defining an interior volume for receiving and holding weighting material.

Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

Science.gov (United States)

Fouda, Usama M; Sayed, Ahmed M

2011-12-01

To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

Developing C# Apps for iPhone and iPad using MonoTouch

CERN Document Server

Costanich, Bryan

2011-01-01

Developing C# Applications for iPhone and iPad using MonoTouch shows you how to use your existing C# skills to write apps for the iPhone and iPad. Fortunately, there's MonoTouch, Novell's .NET library that allows C# developers to write C# code that executes in iOS. Furthermore, MonoTouch allows you to address all the unique functions of the iPhone, iPod Touch, and iPad. And the big plus: You needn't learn any Objective-C to master MonoTouch!. Former Microsoft engineer and published app-store developer Bryan Costanich shows you how to use the tools you already know to create native apps in iOS

Optimal Padding for the Two-Dimensional Fast Fourier Transform

Science.gov (United States)

Dean, Bruce H.; Aronstein, David L.; Smith, Jeffrey S.

2011-01-01

One-dimensional Fast Fourier Transform (FFT) operations work fastest on grids whose size is divisible by a power of two. Because of this, padding grids (that are not already sized to a power of two) so that their size is the next highest power of two can speed up operations. While this works well for one-dimensional grids, it does not work well for two-dimensional grids. For a two-dimensional grid, there are certain pad sizes that work better than others. Therefore, the need exists to generalize a strategy for determining optimal pad sizes. There are three steps in the FFT algorithm. The first is to perform a one-dimensional transform on each row in the grid. The second step is to transpose the resulting matrix. The third step is to perform a one-dimensional transform on each row in the resulting grid. Steps one and three both benefit from padding the row to the next highest power of two, but the second step needs a novel approach. An algorithm was developed that struck a balance between optimizing the grid pad size with prime factors that are small (which are optimal for one-dimensional operations), and with prime factors that are large (which are optimal for two-dimensional operations). This algorithm optimizes based on average run times, and is not fine-tuned for any specific application. It increases the amount of times that processor-requested data is found in the set-associative processor cache. Cache retrievals are 4-10 times faster than conventional memory retrievals. The tested implementation of the algorithm resulted in faster execution times on all platforms tested, but with varying sized grids. This is because various computer architectures process commands differently. The test grid was 512 512. Using a 540 540 grid on a Pentium V processor, the code ran 30 percent faster. On a PowerPC, a 256x256 grid worked best. A Core2Duo computer preferred either a 1040x1040 (15 percent faster) or a 1008x1008 (30 percent faster) grid. There are many industries that

Imaging findings of Hoffa's fat pad herniation

Energy Technology Data Exchange (ETDEWEB)

Chauvin, Nancy A.; Khwaja, Asef [The Children' s Hospital of Philadelphia, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Epelman, Monica [Nemours Children' s Hospital, Department of Medical Imaging, Orlando, FL (United States); Callahan, Michael J. [Harvard Medical School, Department of Radiology, Boston Children' s Hospital, Boston, MA (United States)

2016-04-15

We report the radiologic findings of herniation of Hoffa's fat pad through a defect in the lateral patellar retinaculum in young children who presented with painless masses visible by ultrasound (US) only with flexion of the knee. Six children, between the ages of 1-8 years, presented with an anterolateral knee mass that was not tender and was only seen and palpable with knee flexion. An US was performed in all patients, magnetic resonance imaging (MRI) in 2 patients and knee radiographs in 1 patient. US imaging displayed focal herniation of Hoffa's fat pad within the infrapatellar region through a defect of the lateral retinaculum, visible only during dynamic imaging when the knee was in flexion. MRI performed in knee extension did not demonstrate a mass; however, it revealed a focal defect in the lateral retinaculum in the region of the abnormality. Radiographs were normal. Focal herniation of Hoffa's fat pad is an uncommon cause of an anterolateral knee mass in young children. When a knee mass is only identified in flexion, focal fat herniation through a defect in the retinaculum should be suspected and a dynamic US should be performed. (orig.)

Evaluation of the Thermal Effects in Tilting Pad Bearing

Directory of Open Access Journals (Sweden)

G. B. Daniel

2013-01-01

Full Text Available The analysis of thermal effects is of expressive importance in the context of rotordynamics to evaluate the behavior of hydrodynamic bearings because these effects can influence their dynamic characteristics under specific operational conditions. For this reason, a thermohydrodynamic model is developed in this work, in which the pressure distribution in the oil film and the temperature distribution are calculated together. From the pressure distribution, the velocity distribution field is determined, as well as the viscous dissipation, and consequently, the temperature distribution. The finite volume method is applied to solve the Reynolds equation and the energy equation in the thermohydrodynamic model (THD. The results show that the temperature is higher as the rotational speed increases due to the shear rate of the oil film. The maximum temperature in the bearing occurs in the overloaded pad, near the outlet boundary. The experimental tests were performed in a tilting pad journal bearing operating in a steam turbine to validate the model. The comparison between the experimental and numerical results provides a good correlation. The thermohydrodynamic lubrication developed in this assignment is promising to consistently evaluate the behavior of the tilting pad journal bearing operating in relatively high rotational speeds.

Imaging findings of Hoffa's fat pad herniation

International Nuclear Information System (INIS)

Chauvin, Nancy A.; Khwaja, Asef; Epelman, Monica; Callahan, Michael J.

2016-01-01

We report the radiologic findings of herniation of Hoffa's fat pad through a defect in the lateral patellar retinaculum in young children who presented with painless masses visible by ultrasound (US) only with flexion of the knee. Six children, between the ages of 1-8 years, presented with an anterolateral knee mass that was not tender and was only seen and palpable with knee flexion. An US was performed in all patients, magnetic resonance imaging (MRI) in 2 patients and knee radiographs in 1 patient. US imaging displayed focal herniation of Hoffa's fat pad within the infrapatellar region through a defect of the lateral retinaculum, visible only during dynamic imaging when the knee was in flexion. MRI performed in knee extension did not demonstrate a mass; however, it revealed a focal defect in the lateral retinaculum in the region of the abnormality. Radiographs were normal. Focal herniation of Hoffa's fat pad is an uncommon cause of an anterolateral knee mass in young children. When a knee mass is only identified in flexion, focal fat herniation through a defect in the retinaculum should be suspected and a dynamic US should be performed. (orig.)

40 CFR 270.26 - Special part B information requirements for drip pads.

Science.gov (United States)

2010-07-01

... residuals. (14) A description of how each drip pad, including appurtenances for control of run-on and run..., detailed plans and an engineering report describing how the requirements of § 264.90(b)(2) of this chapter will be met. (c) Detailed plans and an engineering report describing how the drip pad is or will be...

iPad Deployment in a Diverse Urban High School: A Formative Experiment

Science.gov (United States)

Frey, Nancy; Fisher, Douglas; Lapp, Diane

2015-01-01

We explore the use of iPads in a diverse urban high school and the ways in which teachers and students were supported to integrate these tools into their instruction. We provided 4 English teachers with 20 iPads with little or no professional development about how to integrate them into their instruction. Using a formative experiment design, we…

iPads in K-12 Schools: A Grounded Theory Study of Value

Science.gov (United States)

Townsend, Mary Beth

2017-01-01

This qualitative grounded theory study investigated the value of iPads in K-12 schools when used in one-to-one ratios. The purpose of the study was to understand the perspectives of teachers using iPads in one-to-one ratios for teaching and learning in the classroom and administrators responsible for the implementation of these devices. The…

Expectations of iPad Use in an Internal Medicine Residency Program: Is It Worth the “Hype”?

Science.gov (United States)

Luo, Nancy; Chapman, Christopher G; Patel, Bhakti K; Woodruff, James N

2013-01-01

Background While early reports highlight the benefits of tablet computing in hospitals, introducing any new technology can result in inflated expectations. Objective The aim of the study is to compare anticipated expectations of Apple iPad use and perceptions after deployment among residents. Methods 115 internal medicine residents received Apple iPads in October 2010. Residents completed matched surveys on anticipated usage and perceptions after distribution 1 month prior and 4 months after deployment. Results In total, 99% (114/115) of residents responded. Prior to deployment, most residents believed that the iPad would improve patient care and efficiency on the wards; however, fewer residents “strongly agreed” after deployment (34% vs 15% for patient care, PiPad for placing orders post call and during admission (71% vs 44% post call, P=.01, and 16% vs 0% admission, P=.04). Previous Apple iOS product owners were also more likely to use the iPad in key areas. Overall, 84% of residents thought the iPad was a good investment for the residency program, and over half of residents (58%) reported that patients commented on the iPad in a positive way. Conclusions While the use of tablets such as the iPad by residents is generally well received, high initial expectations highlight the danger of implementing new technologies. Education on the realistic expectations of iPad benefits may be warranted. PMID:23656727

"I Have an iPad. Now What?" Using Mobile Devices in University Physical Education Programs

Science.gov (United States)

Rosenthal, Maura B.; Eliason, Susan K.

2015-01-01

In response to an iPad initiative at a mid-sized New England university, all faculty, junior and senior undergraduates, and graduate students were required to have iPads by the first day of class in the fall semester of 2013. Goals of the initiative focused on preparing future teachers to use the iPad as a teaching and learning tool so they could…

Pad printing as a film forming technique for polymer solar cells

Energy Technology Data Exchange (ETDEWEB)

Krebs, Frederik C. [Risoe National Laboratory for Sustainable Energy, Technical University of Denmark, Frederiksborgvej 399, DK-4000 Roskilde (Denmark)

2009-04-15

Pad printing as a technique for preparing the active layer in polymer solar cells is presented. The technique employs a silicone rubber stamp to pick up the motif from a gravure plate and transfer it to the substrate. The strengths and limitations of pad printing are discussed and polymer solar cells prepared by pad printing are presented. Devices were prepared on indium tin oxide substrates but in principle the entire photovoltaic device comprising front and back electrodes, barrier layers and active layer could be printed with no need for vacuum steps. The device geometry comprises a spin coated transparent zinc oxide front electrode, a pad printed active layer based on a bulk heterojunction of the thermocleavable polymer poly(3-(2-methylhexyloxycarbonyl)thiophene-co-thiopene) (P3MHOCT) and zinc oxide nanoparticles, spin coated PEDOT:PSS and finally a manually cast thermally cured silver paste back electrode. The P3MHOCT was converted to poly(3-carboxy-dithiophene) (P3CT) in situ by heating the film to 200 C for a brief period. The entire printing and device preparation was carried out in the ambient atmosphere and the devices obtained had a good stability in air during storage and operation. (author)

Compression Pad Cavity Heating Augmentation on Orion Heat Shield

Science.gov (United States)

Hollis, Brian R.

2011-01-01

An experimental study has been conducted to assess the effects of compression pad cavities on the aeroheating environment of the Project Orion Crew Exploration Vehicle heat shield. Testing was conducted in Mach 6 and 10 perfect-gas wind tunnels to obtain heating measurements in and around the compression pads cavities using global phosphor thermography. Data were obtained over a wide range of Reynolds numbers that produced laminar, transitional, and turbulent flow within and downstream of the cavities. The effects of cavity dimensions on boundary-layer transition and heating augmentation levels were studied. Correlations were developed for transition onset and for the average cavity-heating augmentation.

View and Manage Your Photos on the iPad

CERN Document Server

Biersdorfer, J

2010-01-01

One of the iPad's big pluses is its beautiful, high-resolution display. That makes it a perfect way to stroll down memory lane-from the comfort of your armchair. View and Manage Your Photos on the iPad: The Mini Missing Manual shows you how to import, organize, and enjoy your photos using clear, jargon-free explanations and step-by-step instructions. You'll learn to create slideshows complete with your own soundtrack and transitions, connect your tablet to a big-screen TV so you can gather the family around, turn your slab into a digital picture frame (a great idea when you recharge your 'Pa

Best iPad Apps The Guide for Discriminating Downloaders

CERN Document Server

Meyers, Peter

2010-01-01

What really wows iPad fans is when their touchscreen does what's impossible on other gadgets: the finger-painting app that turns a cross-country flight into a moving art class, the mini music studio (two-dozen instruments strong, each with motion-induced warble effects), and the portable fireworks display that you sculpt by swiping. Problem is, with tens of thousands of apps available for your iPad, who knows what to download? You can try to sort through a gazillion customer reviews with a mix of 5- and 1-star ratings, but that's a head-hurting time-waster. The stakes are getting higher, too

Cefazolin-containing poly(ε-caprolactone sponge pad to reduce pin tract infection rate in rabbits

Directory of Open Access Journals (Sweden)

Hirotaka Mutsuzaki

2014-04-01

Full Text Available In our previous study, a fibroblast growth factor-2 (FGF-2–apatite composite layer coated on titanium screws effectively prevented pin tract infection in rabbits because of enhanced wound healing; however, the FGF-2–apatite composite layers did not completely prevent pin tract infection. Thus, we recently developed a poly(ε-caprolactone (PCL sponge pad embedded with cefazolin sodium (+CEZ, which has a fast-acting bactericidal effect. The pad is placed on the skin around the screws. The purpose of this study was to determine the anti-infective efficacy of the +CEZ pad on the pin–skin interface of the FGF-2–apatite-coated titanium screws. The +CEZ pads were prepared by mixing PCL and CEZ in 1,4-dioxane, followed by freeze-drying and compaction. They were analyzed regarding their surface structure, in vitro CEZ release profile, and bactericidal activity. The FGF-2–apatite-coated screws were implanted percutaneously in bilateral rabbit proximal tibial metaphyses—with and without the +CEZ pad—for 4 weeks (n = 20. The + CEZ pads consisted of a porous matrix of PCL in which CEZ was embedded. The CEZ-release profile showed an initial burst on Day 1 and a sustained release lasting for 30 days. The +CEZ pad retained its bactericidal activity against Staphylococcus aureus after preincubation on an agar plate for 7 days. Based on visual inspection, the pin tract infection rate was successfully reduced from 72.2% to 15.0% with the +CEZ pad (p < 0.05, which reduced the bacterial count, especially S. aureus (p < 0.05. The histological inflammation rate of the soft tissues was also significantly lower with the +CEZ pad than without it (p < 0.05. The pin tract infection rate was reduced to one-fifth with the +CEZ pad. Using it as described improves infection resistance during percutaneous implantation.

Some of the factors influencing the Heel Pad Compressibility Index (HPCI): a literature search

DEFF Research Database (Denmark)

Matteoli, Sara; Wilhjelm, Jens E.; Torp-Pedersen, Soren T.

2009-01-01

The human heel pad is a complex structure that features non-linear visco-elastic characteristics as the majority of the human soft tissues. The biomechanical aspects of the heel pad are still under investigation and the influence of subject factors such as age, weight, gender, height, race......, and body activity have been reported. The aim of this paper is to study the literature in order to identify the influence of subject factors and diseases on the heel pad compressibility index....

Quadriceps fat pad edema: significance on magnetic resonance images of the knee

International Nuclear Information System (INIS)

Shabshin, Nogah; Schweitzer, Mark E.; Morrison, William B.

2006-01-01

While clinically reading magnetic resonance (MR) images of the knees we have occasionally noted edema within the suprapatellar fat pad, with mass effect both on the suprapatellar joint recess posteriorly, and on the quadriceps tendon anteriorly. This MR appearance is analogous to Hoffa's disease described in the infrapatellar fat pad. We sought to evaluate the frequency and pattern of this finding and to provide clinical and histological correlation. The suprapatellar (quadriceps) fat pad was evaluated in 770 consecutive MR examinations (on 1.5 T and 0.3 T) in 736 patients (353 females and 383 males, age range 5-86 years, mean 44.3 years). The MR images were retrospectively evaluated by two observers in consensus for the presence of quadriceps fat pad edema with mass effect. In 46 patients who had intravenous administration of gadolinium, the presence of enhancement was also evaluated. Clinical correlation was performed in abnormal cases; in one patient, 1-year follow-up MRI was evaluated and in one patient a percutaneous biopsy as well as 2-year clinical follow-up was performed. Thirty-two (4.2%) knees in 29 patients showed quadriceps fat pad edema and mass effect. In five of these patients imaging of the contralateral knee was also performed and four of these showed symmetric edema. Another five cases had gadolinium-enhanced images with prominent enhancement. Most patients had clinical symptoms of meniscal tears (n=16, 55%) or anterior knee pain (n=8, 27.6%). (orig.)

Assessment of the Apple iPad as a low-vision reading aid.

Science.gov (United States)

Morrice, E; Johnson, A P; Marinier, J-A; Wittich, W

2017-06-01

PurposeLow-vision clients frequently report having problems with reading. Using magnification, reading performance (as measured by reading speed) can be improved by up to 200%. Current magnification aids can be expensive or bulky; therefore, we explored if the Apple iPad offers comparable performance in improving reading speeds, in comparison with a closed-circuit television (CCTV) video magnifier, or other magnification devices.MethodsWe recruited 100 participants between the ages of 24-97 years, with low vision who were literate and cognitively capable, of whom 57 had age-related macular degeneration. To assess reading, participants read standardized iReST texts and were tested for comprehension. We compared reading speed on the Apple iPad (10 inch) with that of the CCTV, home magnification devices, and baseline measures.ResultsAll assistive devices improved reading rates in comparison to baseline (P1), however, there was no difference in improvement across devices (P>0.05, Hedge's gread, on average, 30 words per minute faster than first time iPad users, whereas CCTV experience did not influence reading speed.ConclusionsIn our sample, the Apple iPad was as effective as currently used technologies for improving reading rates. Moreover, exposure to, and experience with the Apple iPad might increase reading speed with that device. A larger sample size, however, is needed to do subgroup analysis on who would optimally benefit from each type of magnification device.

Bortezomib prevents acute doxorubicin ovarian insult and follicle demise, improving the fertility window and pup birth weight in mice.

Directory of Open Access Journals (Sweden)

Elon C Roti Roti

Full Text Available Increasing numbers of female patients survive cancer, but succumb to primary ovarian insufficiency after chemotherapy. We tested the hypothesis that Bortezomib (Bort protects ovaries from doxorubicin (DXR chemotherapy by treating female mice with Bort 1 hour prior to DXR. By preventing DXR accumulation in the ovary, Bort attenuated DXR-induced DNA damage in all ovarian cell types, subsequent γH2AFX phosphorylation, and resulting apoptosis in preantral follicles. Bort pretreatment extended the number of litters per mouse, improved litter size and increased pup weight following DXR treatment, thus increasing the duration of post-chemotherapy fertility and improving pup health. As a promising prophylactic ovoprotective agent, Bort does not interfere with cancer treatment, and is currently used as a chemotherapy adjuvant. Bort-based chemoprotection may preserve ovarian function in a non-invasive manner that avoids surgical ovarian preservation, thus diminishing the health complications of premature menopause following cancer treatment.

Novel electrochemical approach to study corrosion mechanism of Al-Au wire-bond pad interconnections

DEFF Research Database (Denmark)

Elisseeva, O. V.; Bruhn, A.; Cerezo, J.

2013-01-01

A gold-aluminium material combination is typically employed as an interconnection for microelectronic devices. One of the reliability risks of such devices is that of corrosion of aluminium bond pads resulting from the galvanic coupling between an aluminium bond pad and a gold wire. The research...... presented in this manuscript focuses on studying bond pad corrosion by selecting an appropriate model system and a dedicated set of electrochemical and analytical experimental tools. Taking into account the complex three-dimensional structure and the small dimensions of Au-Al interconnections (around 50......-100 μm), a dedicated and novel experimental approach was developed. Au-Al covered silicon chips were developed under clean room conditions. Three-dimensional electrodes were mimicked as flat, two-dimensional bond pad model systems, allowing the use of microelectrochemical local probe techniques. Thin...

Characterisation of Silicon Pad Diodes

CERN Document Server

Hodson, Thomas Connor

2017-01-01

Silicon pad sensors are used in high luminosity particle detectors because of their excellent timing resolution, radiation tolerance and possible high granularity. The effect of different design decisions on detector performance can be investigated nondestructively through electronic characterisation of the sensor diodes. Methods for making accurate measurements of leakage current and cell capacitance are described using both a standard approach with tungsten needles and an automated approach with a custom multiplexer and probing setup.

Comparison of therapist implemented and iPad-assisted interventions for children with autism.

Science.gov (United States)

Lee, Allyson; Lang, Russell; Davenport, Katy; Moore, Melissa; Rispoli, Mandy; van der Meer, Larah; Carnett, Amarie; Raulston, Tracy; Tostanoski, Amy; Chung, Clare

2015-04-01

This study compares intervention delivered by a therapist to intervention delivered using an iPad for two children with autism. Further, this study evaluates the influence of choice between the conditions. Time on-task, challenging behaviour, session duration and correct responses were compared across conditions in an alternating treatment design. The effect of choice was evaluated in an ABAB design. The iPad was associated with shorter intervention sessions, more time on-task and less challenging behaviour for one participant. There was no difference between conditions for the second participant. Both participants selected the iPad when given the choice and, although the effect of choice was modest, choosing was associated with more time on-task and less challenging behaviour. These data suggest that iPad-assisted intervention can be as effective as therapist-implemented intervention. Further, even for children for whom no differences between the interventions exist, offering a choice may be beneficial.

Head First iPhone and iPad Development A Learner's Guide to Creating Objective-C Applications for the iPhone and iPad

CERN Document Server

Pilone, Dan

2011-01-01

Let's say you have a killer app idea for iPhone and iPad. Where do you begin? Head First iPhone and iPad Development will help you get your first application up and running in no time. You'll not only learn how to design for Apple's devices, you'll also master the iPhone SDK tools -- including Interface Builder, Xcode, and Objective-C programming principles -- to make your app stand out. Whether you're a seasoned Mac developer who wants to jump into the App store, or someone with strong object-oriented programming skills but no Mac experience, this book is a complete learning experience for

Dealing with large-scale supply lines when introducing new regimens.

Science.gov (United States)

Malati, Christine; Rosenfeld, Joshua; Mowafy, Sherif; Rittmiller, Trevor; Kuritsky, Joel; Crowley, John

2017-07-01

As programs plan the introduction of a new antiretroviral as part of a regimen for HIV treatment, supply chain considerations need to be taken into account. The key to success is balancing the introduction of a new regimen with the phasing out of an old regimen in a manner that does not result in either a shortage or an excess supply of either product while ensuring that patients continue receiving their medications. This necessitates that country programs, donors, and procurement entities possess an appreciation of the global antiretroviral market and understand the dynamics that the manufacturing of new antiretrovirals will have on the transition. Supply, demand, and financial considerations affect the capacity of the supply chain to facilitate a successful antiretroviral transition. Although this commentary draws on United States Agency for International Development experiences under the President's Emergency Plan for AIDS Relief from earlier antiretroviral treatment shifts, the approaches are applicable to other institutions and to future transitions. Three approaches were employed: ensuring the engagement of all key stakeholders in transition planning and execution, including clinicians, advocacy groups, supply chain professionals, ministry, and donors; conducting and updating regularly the national quantification and supply plans for all regimens; and introducing antiretroviral products into programs from regional warehouses based on firm orders. Extensive planning and accounting for supply chain factors is essential to ensuring a smooth transition to a new regimen and to enable the global antiretroviral market to respond adequately.

ImagePAD, a Novel Counting Application for the Apple iPad®, Used to Quantify Axons in the Mouse Optic Nerve

Science.gov (United States)

Templeton, Justin P.; Struebing, Felix L.; Lemmon, Andrew; Geisert, Eldon E.

2014-01-01

The present article introduces a new and easy to use counting application for the Apple iPad. The application “ImagePAD” takes advantage of the advanced user interface features offered by the Apple iOS® platform, simplifying the rather tedious task of quantifying features in anatomical studies. For example, the image under analysis can be easily panned and zoomed using iOS-supported multi-touch gestures without losing the spatial context of the counting task, which is extremely important for ensuring count accuracy. This application allows one to quantify up to 5 different types of objects in a single field and output the data in a tab-delimited format for subsequent analysis. We describe two examples of the use of the application: quantifying axons in the optic nerve of the C57BL/6J mouse and determining the percentage of cells labeled with NeuN or ChAT in the retinal ganglion cell layer. For the optic nerve, contiguous images at 60× magnification were taken and transferred onto an Apple iPad®. Axons were counted by tapping on the touch-sensitive screen using ImagePAD. Nine optic nerves were sampled and the number of axons in the nerves ranged from 38872 axons to 50196 axons with an average of 44846 axons per nerve (SD = 3980 axons). PMID:25281829

Microstructural evaluation of interfacial intermetallic compounds in Cu wire bonding with Al and Au pads

International Nuclear Information System (INIS)

Kim, Hyung Giun; Kim, Sang Min; Lee, Jae Young; Choi, Mi Ri; Choe, Si Hyun; Kim, Ki Hong; Ryu, Jae Sung; Kim, Sangshik; Han, Seung Zeon; Kim, Won Yong; Lim, Sung Hwan

2014-01-01

A comparative study on the difference in interfacial behavior of thermally aged Cu wire bonding with Al and Au pads was conducted using transmission electron microscopy. During high-temperature lifetime testing of Cu wire bonding with Al and Au pads at 175 °C for up to 2000 h, different growth rates and growth characteristics were investigated in the Cu–Al intermetallic compounds (IMCs), including CuAl 2 , CuAl and Cu 9 Al 4 , and in the Cu–Au IMCs, including (Au,Cu), Cu 3 Au and (Cu,Au). Because of the lower growth rates and greater ductility of Cu–Au IMCs compared to those of Cu–Al IMCs, the Cu wire bonding with the Au pad showed relatively better thermal aging properties of bond pull strength and ball shear strength than those with the Al pad counterpart. In this study, the coherent interfaces were found to retard the growth of IMCs, and a variety of orientation relationships between wire, pad and interfacial IMCs were identified

High-pitch metal-on-glass technology for pad pitch adaptation between detectors and readout electronics

CERN Document Server

Ullán, Miguel; Campabadal, Francesca; Fleta, Celeste; Garcia, Carmen; Gonzalez, Francisco; Bernabeu, Jose

2004-01-01

Modern high-energy physics and astrophysics strip detectors have increased channel density to levels at which their connection with readout electronics has become very complex due to high pad pitch. Also, direct wire bonding is prevented by the fact that typically detector's pad pitch and electronics' pad pitch do not match. A high- pitch metal-on-glass technology is presented, that allows pad pitch adaptation between detectors and readout electronics. It consists of high-density metal lines on top of an insulating glass substrate. A photoresist layer is deposited covering the metal tracks for passivation and protection The technology is tested for conductivity, bondability, bonding pull force, peel off, and radiation hardness, and it is an established technology in the clean room of the CNM Institute in Barcelona. This technology has been chosen by the ATLAS Collaboration for the pad pitch adapters (PPA) of the SCT Endcap Modules, by a Compton camera project, and by other HEP groups for interconnection betwe...

Do foot pad scores measure Turkey welfare

NARCIS (Netherlands)

Hocking, P.M.; Harkness, A.; Veldkamp, Teun; Vinco, L.J.

2017-01-01

The main aim of the project was to assess the painfulness of different levels of foot pad dermatitis (FPD) in turkeys. Three different analgesics (butorphanol, carprofen and meloxicam) were used to assess their effect on behaviour. Video recordings were taken when the birds were treated with either

Study on the prevention of spragging in a tilting pad journal bearing using the variation of preload

International Nuclear Information System (INIS)

Yang, Seong Heon; Park, Chul Hyun; Ha, Hyun Cheon; Kim, Chae Sil

2001-01-01

Tilting pad journal bearings have been widely used in a high speed rotating machinery, such as steam turbines and gas turbines, owing to their inherent stability characteristics. However, some peculiar fatigue failure in the babbitt metal due to spragging has been continuously occurred at the leading edge of the upper pads. The spragging is defined as the pad vibration initiated on the upper unloaded pads in tilting pad journal bearing. This paper describes both several kinds of bearing failure related with spragging and the theoretical investigation on the prevention of the spragging phenomenon using the variation of preload. Results show that positive preload(m>0.5) assures all pads remain statically loaded under all operating conditions. For the change of design parameter to prevent spragging, thermo-hydrodynamic lubrication and rotor dynamic analysis were performed to verify temperature limitation on bearing and vibration problems on rotor bearing system

Wet adhesion with application to tree frog adhesive toe pads and tires

International Nuclear Information System (INIS)

Persson, B N J

2007-01-01

Strong adhesion between solids with rough surfaces is only possible if at least one of the solids is elastically very soft. Some lizards and spiders are able to adhere (dry adhesion) and move on very rough vertical surfaces due to very compliant surface layers on their attachment pads. Flies, bugs, grasshoppers and tree frogs have less compliant pad surface layers, and in these cases adhesion to rough surfaces is only possible because the animals inject a wetting liquid into the pad-substrate contact area, which generates a relative long-range attractive interaction due to the formation of capillary bridges. In this presentation I will discuss some aspects of wet adhesion for tree frogs and give some comments related to tire applications

Wet adhesion with application to tree frog adhesive toe pads and tires

Energy Technology Data Exchange (ETDEWEB)

Persson, B N J [IFF, FZ-Juelich, 52425 Juelich (Germany)

2007-09-19

Strong adhesion between solids with rough surfaces is only possible if at least one of the solids is elastically very soft. Some lizards and spiders are able to adhere (dry adhesion) and move on very rough vertical surfaces due to very compliant surface layers on their attachment pads. Flies, bugs, grasshoppers and tree frogs have less compliant pad surface layers, and in these cases adhesion to rough surfaces is only possible because the animals inject a wetting liquid into the pad-substrate contact area, which generates a relative long-range attractive interaction due to the formation of capillary bridges. In this presentation I will discuss some aspects of wet adhesion for tree frogs and give some comments related to tire applications.

Using iPad-Based Mobile Learning to Teach Creative Engineering within a Problem-Based Learning Pedagogy

Science.gov (United States)

Li, Yulong; Wang, Lixun

2018-01-01

This case study, noting the increasing interest in iPad-based mobile learning research and aware of the current dearth of engineering talent in the UK, aims to contribute to a still sparse area of research that links iPad use to engineering education. To achieve this, the study investigates the integration of iPad-based mobile learning…

iPad® Use in Children and Young Adults with Autism Spectrum Disorder: An Observational Study

Science.gov (United States)

King, Amie M.; Thomeczek, Melissa; Voreis, Grayce; Scott, Victoria

2014-01-01

This exploratory study was conducted to describe how children and young adults with autism spectrum disorder (ASD) are currently using iPads® and applications, to explore the role of education professionals on iPad® and application use, and to determine potential research needs regarding iPad® use in children with ASD. Naturalistic observations…

Analysis of a hypothetical dropped spent nuclear fuel shipping cask impacting a floor mounted crush pad

International Nuclear Information System (INIS)

Hawkes, B.D.; Uldrich, E.D.

1998-03-01

A crush pad has been designed and analyzed to absorb the kinetic energy of a hypothetically dropped spent nuclear fuel shipping cask into a 44-ft. deep cask unloading pool at the Idaho Chemical Processing Plant. The 110-ton Large Cell Cask was assumed to be accidentally dropped onto the parapet of the unloading pool, causing the cask to tumble through the pool water and impact the floor mounted crush pad with the cask's top corner. The crush pad contains rigid polyurethane foam, which was modeled in a separate computer analysis to simulate the manufacturer's testing of the foam and to determine the foam's stress and strain characteristics. This computer analysis verified that the foam was accurately represented in the analysis to follow. A detailed non-linear, dynamic finite element analysis was then performed on the crush pad and adjacent pool structure to assure that a drop of this massive cask does not result in unacceptable damage to the storage facility. Additionally, verification was made that the crush pad adequately protects the cask from severe impact loading. At impact, the cask has significant vertical, horizontal and rotational velocities. The crush pad absorbs much of the energy of the cask through plastic deformation during primary and secondary impacts. After the primary impact with the crush pad, the cask still has sufficient energy to rebound and rotate until it impacts the pool wall. An assessment is made of the damage to the crush pad and pool wall and of the impact loading on the cask

The role of the iPad in collaborative learning in a large-enrollment first-year physics module

Science.gov (United States)

van der Ventel, Brandon; Newman, Richard; Botes, Lise; Goldberg, Alan

2016-07-01

The role of the iPad was investigated in the possible enhancement of collaborative learning within a tutorial setting in a large-enrollment first-year physics module. Every tutorial session was divided into an ‘iPad group’ and a ‘non-iPad group’. A set of core apps was chosen to facilitate discussion within the group. In order to maintain parity across the two groups, all the tutorial questions had to be refitted into a form suitable for use with the iPad. The results of a survey done after each tutorial indicates that, qualitatively, the iPad significantly enhanced the learning experience and strongly contributed to discussion within the group.

iPads and LCDs show similar performance in the detection of pulmonary nodules

Science.gov (United States)

McEntee, Mark F.; Lowe, Joanna; Butler, Marie Louise; Pietrzyk, Mariusz; Evanoff, Michael G.; Ryan, John; Brennan, Patrick C.; Rainford, Louise A.

2012-02-01

In February 2011 the University of Chicago Medical School distributed iPads to its trainee doctors for use when reviewing clinical information and images on the ward or clinics. The use of tablet computing devices is becoming widespread in medicine with Apple™ heralding them as "revolutionary" in medicine. The question arises, just because it is technical achievable to use iPads for clinical evaluation of images, should we do so? The current work assesses the diagnostic efficacy of iPads when compared with LCD secondary display monitors for identifying lung nodules on chest x-rays. Eight examining radiologists of the American Board of Radiology were involved in the assessment, reading chest images on both the iPad and the an off-the-shelf LCD monitor. Thirty chest images were shown to each observer, of which 15 had one or more lung nodules. Radiologists were asked to locate the nodules and score how confident they were with their decision on a scale of 1-5. An ROC and JAFROC analysis was performed and modalities were compared using DBM MRMC. The results demonstrate no significant differences in performance between the iPad and the LCD for the ROC AUC (p<0.075) or JAFROC FOM (p<0.059) for random readers and random cases. Sample size estimation showed that this result is significant at a power of 0.8 and an effect size of 0.05 for ROC and 0.07 for JAFROC. This work demonstrates that for the task of identifying pulmonary nodules, the use of the iPad does not significantly change performance compared to an off-the-shelf LCD.

A pilot trial of the iPad tablet computer as a portable device for visual acuity testing.

Science.gov (United States)

Zhang, Zhao-tian; Zhang, Shao-chong; Huang, Xiong-gao; Liang, Ling-yi

2013-01-01

We evaluated the accuracy of an app for the iPad tablet computer (Eye Chart Pro) as a portable method of visual acuity (VA) testing. A total of 120 consecutive patients (240 eyes) underwent visual acuity test with an iPad 2 and a conventional light-box chart. The logMAR VA results from the iPad were significantly higher than those from the light-box (P iPad chart and the light-box chart, with 95% limits of agreement of -0.14 to 0.19. Two groups of patients were defined: in Group 1 there were 182 eyes with VA better than 0.1 according to the light-box VA test. The median logMAR VA by the iPad was 0.54 and by the light-box chart it was 0.52; there was no significant difference between them (P = 0.69). In Group 2 there were 58 eyes with VA equal to or worse than 0.1 according to the light-box VA test. The median logMAR VA by the iPad was 1.26 and was 1.10 by the light box; the result from the iPad was significantly lower (P iPad is reliable for VA testing only when the Snellen VA is better than 0.1 (20/200).

Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

Directory of Open Access Journals (Sweden)

Catriona Elizabeth Mactier

2012-10-01

Full Text Available Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

Cleansing the colon in gallium-67 scintigraphy: a prospective comparison of regimens

International Nuclear Information System (INIS)

Novetsky, G.J.; Turner, D.A.; Ali, A.; Raynor, W.J.; Fordham, E.W.

1981-01-01

Colonic accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. Although various modes of cleansing the colon prior to scintigraphy have been suggested, there is controversy over their efficacy and none have been tested prospectively. Three hundred nine patients undergoing gallium-67 scintigraphy were randomly assigned to one of four cleansing regimens: (1) a high fiber diet (78 patients); (2) castor oil (76); (3) milk of magnesia and cascara (76); and (4) no preparation (79). Patient compliance rates for the four regimens were 17%, 32%, 36%, and 46%, respectively. After noncompliant patients were excluded, gallium-67 scintigrams were graded for colonic activity on a scale of 0-3 by three independent, experienced observers. Gallium-67 activity in the colon was significantly less after adminstration of castor oil than after no prepartion (p = 0.083). Regimen 3 did not produce significantly better results than regimen 4 (p = 0.42). A major impediment to the success of any cleansing regimen seems to be poor compliance of patients

Smoking is associated with increased levels of extracellular peptidylarginine deiminase 2 (PAD2) in the lungs

DEFF Research Database (Denmark)

Damgaard, Dres; Friberg Bruun Nielsen, Michael; Quisgaard Gaunsbaek, Maria

2015-01-01

lavage (BAL) fluid from smokers, but intracellularly located PAD cannot be responsible for citrullination of extracellular self-antigens. We aimed to establish a link between smoking and extracellular PAD2 in the lungs. METHODS: BAL fluid samples were obtained from 13 smokers and 11 nonsmoking controls...... fluids from smokers as compared to non-smokers (p=0.018). The PAD2 content correlated with the overall CRP levels (p=0.009) and cell count (p=0.016). CONCLUSIONS: This first demonstration of increased levels of extracellular PAD2 in the lungs of smokers supports the hypothesis that smoking promotes...

49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

Science.gov (United States)

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Brake actuators, slack adjusters, linings/pads and..., slack adjusters, linings/pads and drums/rotors. (a) General requirements. Brake components must be... same size. (c) Slack adjusters. The effective length of the slack adjuster on each end of an axle must...

Thermal–Hydrodynamic Behaviour of Coated Pivoted Pad Thrust Bearings: Comparison between Babbitt, PTFE and DLC

Directory of Open Access Journals (Sweden)

Konstantinos Katsaros

2018-05-01

Full Text Available The hydrodynamic lubrication and thermal analysis of tilting pad thrust bearings has been a major subject for many studies in the field of tribology. There is only a limited number of studies regarding thrust bearings with coated surfaces. The purpose of this study is to build a parametric, iterative algorithm in order to perform a complete thermal and hydrodynamic lubrication analysis for pivoted pad thrust bearings with coatings. The analytical model is mainly based on the energy, continuity and Navier–Stokes equations, which are solved numerically with the Semi-Implicit Method for Pressure Linked Equations Consistent (SIMPLEC method. The analysis focuses on a single pivoted pad of the thrust bearing. The thermal properties of the coating material are taken into account and the resulting thermal and flow fields are solved. The basic hydrodynamic and tribological characteristics are calculated for an uncoated, a Babbitt coated, a PTFE coated and a diamond like carbon (DLC coated pivoted pad thrust bearing. The pressure and the film thickness distribution, as well as the load capacity and the frictional forces, are determined for several pad positions and velocities of the rotor. A mineral oil lubricant is used to estimate the shear thinning or thickening effects on the pad tribological performance. The results indicate that pads coated with PTFE and DLC show lower friction forces compared to the common steel and Babbitt applications. At the same time, the DLC coating seems to affect the bearing’s flow and thermal fields less than the PTFE, making it more suitable for thrust bearings applications.

190-C Facility <90 Day Storage Pad training plan

International Nuclear Information System (INIS)

Little, N.C.

1996-12-01

This is the Environmental Restoration Contractor (ERC) team training plan for the 190-C Facility <90 Day Storage Pad of Hazardous Waste. It is intended to meet the requirements of Washington Administrative Code (WAC) 173-303-330 and the Hanford Dangerous Waste Permit. Training unrelated to compliance with WAC 173-303-330 is not addressed in this training plan. WAC 173-303-330(1)(d)(ii, v, vi) requires that personnel be familiarized, where applicable, with waste feed cut-off systems, response to ground-water contamination incidents, and shutdown of operations. These are not applicable to 190-C Facility <90 Day Storage Pad, and are therefore not covered in this training plan

Design charts for arbitrarily pivoted, liquid-lubricated flat-sector-pad thrust bearing

Science.gov (United States)

Etsion, I.

1977-01-01

A flat, sector-shaped geometry for a liquid-lubricated thrust bearing is analyzed considering both the pitch and roll of the pad. Results are presented in design charts that enable a direct approach to the design of point- and line-pivoted, tilting pad bearings. A comparison is made with the Mitchell bearing approximation and it is found that this approximation always overestimates load capacity.

Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians.

Science.gov (United States)

Nappi, Rossella E; Kaunitz, Andrew M; Bitzer, Johannes

2016-01-01

The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices.

Accumulation of Arsenic and Mercury in Different Bio-bed Padding Materials

Directory of Open Access Journals (Sweden)

LIU Tian-yu

2016-07-01

Full Text Available In order to study the accumulation and distribution of As, Hg in different bio-bed padding materials while implementing bio-bed raising method, three kinds of bio-bed padding materials were well designed, which consisted of sawdust(S, sawdust + rice husk(SR and sawdust + rice husk + straw(SRS. For a year and a half, the contents of As, Hg at different depth were measured when four groups of fattening pig breeding had finished to analyze the accumulation and distribution of As, Hg in different bio-bed padding materials, which could provide a theoretical basis for follow-up application of bio-bed padding materials in agriculture. The results showed that, the accumulation of As and Hg, at different levels, occurred during four pig-raising cycles. When 4 groups of fattening pig breeding finished, the largest accumulation of As and Hg occurred in SRS bio-beds, respectively reached 1921.7 mg per sty and 21.1 mg per sty. The As and Hg contents of S, SR,SRS were 2.921, 2.190, 2.621 mg·kg-1 and 0.048, 0.036, 0.042 mg·kg-1, respectively, which met the China's Organic Fertilizer Agriculture Standards(NY 525-2012, and Farmland Environmental Quality Evaluation Standards For Edible Agricultural Products(HJ/T 332-2006.

Launch Pad Coatings for Smart Corrosion Control

Science.gov (United States)

Calle, Luz M.; Hintze, Paul E.; Bucherl, Cori N.; Li, Wenyan; Buhrow, Jerry W.; Curran, Jerome P.; Whitten, Mary C.

2010-01-01

Corrosion is the degradation of a material as a result of its interaction with the environment. The environment at the KSC launch pads has been documented by ASM International (formerly American Society for Metals) as the most corrosive in the US. The 70 tons of highly corrosive hydrochloric acid that are generated by the solid rocket boosters during a launch exacerbate the corrosiveness of the environment at the pads. Numerous failures at the pads are caused by the pitting of stainless steels, rebar corrosion, and the degradation of concrete. Corrosion control of launch pad structures relies on the use of coatings selected from the qualified products list (QPL) of the NASA Standard 5008A for Protective Coating of Carbon Steel, Stainless Steel, and Aluminum on Launch Structures, Facilities, and Ground Support Equipment. This standard was developed to establish uniform engineering practices and methods and to ensure the inclusion of essential criteria in the coating of ground support equipment (GSE) and facilities used by or for NASA. This standard is applicable to GSE and facilities that support space vehicle or payload programs or projects and to critical facilities at all NASA locations worldwide. Environmental regulation changes have dramatically reduced the production, handling, use, and availability of conventional protective coatings for application to KSC launch structures and ground support equipment. Current attrition rate of qualified KSC coatings will drastically limit the number of commercial off the shelf (COTS) products available for the Constellation Program (CxP) ground operations (GO). CxP GO identified corrosion detection and control technologies as a critical, initial capability technology need for ground processing of Ares I and Ares V to meet Constellation Architecture Requirements Document (CARD) CxP 70000 operability requirements for reduced ground processing complexity, streamlined integrated testing, and operations phase affordability

KONTRIBUSI TAMAN WISATA ALAM BANTIMURUNG TERHADAP PENDAPATAN ASLI DAERAH (PAD KABUPATEN MAROS

Directory of Open Access Journals (Sweden)

Nur Fitri Syam

2017-06-01

Full Text Available Fitri Nur Syam, 2016. "The Contribution of the Nature Park Bantimurung Against Local Revenue (PAD Maros". Thesis Supervised by Dr. H. A. Arifuddin Mane, SE, M.Si, SH, MH as a supervisor I and Drs.Syamsuddin Djafar SE., M.Si as Supervisor II. This study aims to determine the magnitude Contributions Levy Park Nature Bantimurung to local revenue (PAD Maros. The research was conducted at the Department of Tourism and Maros. Data used in the thesis, is derived from PAD report Maros 2011-2013 period and some literature review. Data analysis method used is descriptive analysis method is to describe how much the contribution levy Bantimurung Against Nature Park Local Revenue Maros. Based on the results of the analysis that the value of PAD acceptance Maros continuously increased from 2011 to 2015. On the other hand, the value of levy receipts TWAB fluctuate, ie from 2011 to 2012 has increased the amount of Rp 2,596,094,700, an increase amounting to 57.65%, whereas from 2012 to 2013 the value of the levy TWAB decreased by Rp 1,977,385,700, or decreased (-27.8%. Selanjutanya, from 2013 to 2014 the value of retribution TWAB rise again, but the increase is small with only Rp 1,538,205,400, an increase of 30.03%. But from 2014 to 2015 the value of retribution decreased again by Rp 227 134 100 or decreased (-3.4%. In general, the value of the contribution to the PAD TWAB Maros from 2011-2015 epidemic is still relatively small, even declining since 2013. From the calculation of value contribution TWAB retribution against PAD Maros years 2011-2015 shows that the greatest value of the contribution that only happens in 2012 which reached 8.26%, while the value of the contribution of three years thereafter relatively small, especially in 2015 which only amounted to 4.61%.

Analysing the protective potential of padded soccer goalkeeper shorts.

Science.gov (United States)

Schmitt, K U; Nusser, M; Derler, S; Boesiger, P

2010-05-01

In this study, the potential of currently available padded soccer goalkeeper shorts to prevent hip injuries sustained in side jumps was investigated. Within the scope of this study, a survey among professional and amateur goalkeepers, trainers and the medical staff was performed. In addition, commercially available shorts were impact-tested using an artificial hip model. The results were compared with requirements established for hip protectors for elderly. The results of the survey found that contusions and abrasions were observed most often for all players. Fractures and arthritis were only reported by amateur players, whereas bursitis was more frequently observed by professional players. Amateurs have a significantly higher risk of injury than professional players, and the higher injury risk during training is significantly higher compared with the injury risk during a match. No difference of the injury risk was found between goalkeepers wearing padded shorts and those who did not. Impact tests indicated a wide range of performance of the currently available products. The padded shorts generally reduce impact forces, but mostly perform poorly. Only shorts that were made of visco-elastic foam fulfilled the basic requirements requested for hip protectors for elderly. The quality of most of the currently available goalkeeper shorts needs to be improved to effectively prevent hip injury sustained in side jumps.