Maximum Number Of Cycles Research Articles

Rapid Flow Injection Electrochemical Detection of Arochlor 1242 Using Stabilized Lipid Membranes with Incorporated Sheep anti‐PCB Antibody

AbstractThis work describes a novel electrochemical biosensor based on a supported polymerized lipid film with incorporated Sheep anti‐PCB antibody for the rapid detection of arochlor 1242 in flowing solution streams. The antibody was incorporated into the lipid film during polymerization. Injections of antigen were made into flowing streams of a carrier electrolyte solution. Experiments were done in a stopped‐flow mode using lipid mixtures containing 15 % (w/w) dipalmitoylphosphatidic acid (DPPA) to provide only a single transient current signal with a magnitude related to the antigen concentration. Lipid films containing 35 % DPPA were used to examine regeneration of the active sites of antibody after complex formation by washing with the carrier electrolyte solution. Repetitive cycles of injection of antigen have shown that the maximum number of cycles is about 5.

Low voltage cycling of programmable metallization cell memory devices

Future nanoscale memory technologies must ultimately be able to operate atpower supply voltages in the order of 0.6 V or less. We have demonstratedin this work that it is possible to utilize symmetric program–erase (P–E)cycling for Ag/Ag–Ge–S/W programmable metallization cell devices at voltagesbelow 0.6 V and still maintain an OFF/ON resistance ratio well in excessor 10 over a wide range of program and erase currents (0.27, 1.6, 55 and 220 µA) as set by a series resistance. The distributions of resistance values for104 P–E cycles indicate that the margins between the highest on- and lowest off-state resistancesare sufficient for unambiguous differentiation in all but the lowest current case in which there issome overlap. In addition, there is no substantial change in switching speed for up to1.5 × 106 P–E operations, the maximum number of cycles attempted in this study.

Do Locked Compression Intramedullary Nails Improve the Biomechanical Stability of Distal Femoral Fractures?

A distal femur nail with fixed-angle locking screws intends to combine the advantages of angular stability and intramedullary stabilization in extraarticular distal femur fractures. The goal of this study was to analyze whether the locked compression distal femur nail (LCN) was biomechanically more stable than a conventional standard distal femur nail (CN). Both nails were compared on a series of 10 matched pairs of human femora. After setting a distal femur defect fracture, the intramedullary stabilized femur was axially loaded starting from 100 N, increasing in steps of 100 N after every 200 cycles with a triangular frequency of 1 Hz, until a predefined point of failure was reached. The two types of nails showed no significant difference in terms of maximum tolerated load, maximum number of cycles repeated, or axial deformation of the bone-implant construct. The mean load at failure was 2,954 N for the CN and 2,483 N for the LCN. The mean axial deformation for the conventional (14.8 mm) and locked compression nail (15.3 mm) did not differ significantly. Mode of failure was a bony fracture in all specimens predominantly involving the proximal femur. No significant difference in stability between the two compared implants could be demonstrated. The LCN showed comparable characteristics under cyclic axial loading as the conventional distal femur nail. No migration into the articular space or implant failure was observed.

On the Maximum Number of Cycles in Outerplanar and Series–Parallel Graphs

Let c(n) be the maximum number of cycles in an outerplanar graph with n vertices. We show that lim c(n)1/n exists and equals β = 1.502837 . . ., where β is a constant related to the recurrence $${x_{n+1} = 1 + x_n^2, \, x_0=1}$$. The same result holds for the larger class of series–parallel graphs.

Threaded Screw Head Inserts Improve Locking Plate Biomechanical Properties

The purpose of this study was to determine if the stiffness and fatigue life of locking one third tubular plates are enhanced by placing a locking screw head to fill the empty hole of the plate. We hypothesize that both the stiffness and fatigue life of the plates will be improved at physiologically relevant loads by filling the empty center hole of each plate. The mechanical stiffness and fatigue life of plates with an open versus filled center hole were assessed through finite element analysis and experimentally using a synthetic bone model under four-point bending. Two plate manufacturers were evaluated, Synthes (n) and Stryker (r). Five-hole one third tubular plates were mechanically cycled with and without filling the central screw hole while load, displacement, and number of cycles were collected. Stiffness was calculated and cycles to failure and mode of failure were monitored. Five plates were evaluated for the filled (F) and open (O) configurations for the n and r plates. Finite element analysis indicated that filling the hole resulted in reduction in maximum stress at the periphery of the center hole by a factor of 2.43 and 2.29 for the n and r plates, respectively. Experimentally, a fourfold improvement was observed in fatigue life of the Synthes plates when a screw head was used to fill the central screw hole (P < 0.005; nF = 45,450 cycles versus nO = 10,305 cycles). The Stryker plates reached the maximum number of cycles (1 million) without fatigue failure in both O and F configurations. Improved bending stiffness was noted for both the n and r plates when the central hole was filled compared with open. For the Stryker plate, this increase was statistically significant (P < 0.011). The methodology proposed in this study for extending fatigue life and increasing stiffness of locking plates can potentially be extended to any locking plate. Adding a screw head or screw heads to open holes in locking plates adds little additional time or expense and no morbidity to the procedure but can have substantial effects on the mechanical properties of the implant, particularly in lower-profile plates that are initially less rigid and robust.

Bounds for chromatic number in terms of even-girth and booksize

The even-girth of any graph G is the smallest length of any even cycle in G . For any two integers t , k with 0 ≤ t ≤ k − 2 , we denote the maximum number of cycles of length k such that each pair of cycles intersect in exactly a unique path of length t by b t , k ( G ) . This parameter is called the ( t , k ) -booksize of G . In this paper we obtain some upper bounds for the chromatic and coloring numbers of graphs in terms of even-girth and booksize. We also prove some bounds for graphs which contain no cycle of length t where t is a small and fixed even integer.

Adequacy of Published Oncology Randomized Controlled Trials to Provide Therapeutic Details Needed for Clinical Application

Randomized controlled trials (RCTs) improve clinical care through evidence-based results. Guidelines exist for RCT result reporting, but specific details of therapeutic administration promote clinical application and reproduction of the trial design. We assess the reporting methodology in RCTs published in major oncology journals. Ten essential elements of RCT reporting were identified and included drug name, dose, route, cycle length, maximum number of cycles, premedication, growth factor support, patient monitoring parameters, and dosing adjustments for hematologic and organ-specific toxicity. All therapy-based oncology RCTs published between 2005 and 2008 in the New England Journal of Medicine (NEJM), Journal of Clinical Oncology (JCO), Journal of the National Cancer Institute (JNCI), Blood, and Cancer were analyzed for inclusion of these 10 elements. Of 339 identified articles, 262 were included in the final analysis (165 from JCO, 31 from NEJM, 27 from Cancer, 20 from JNCI, and 19 from Blood). Premedication, growth factor support, and dose adjustments for toxicities were each reported less than half of the time. Only 30 articles (11%) met the main objective of complete data reporting (ie, all 10 essential elements) and was highest in JNCI (5/20; 25%), followed by Cancer (5/27; 18%), JCO (18/165; 11%), Blood (1/19; 5%), and NEJM (1/31; 3%). The presence of an online appendix did not substantially improve complete reporting. RCTs published in major oncology journals do not consistently report essential therapeutic details necessary for translation of the trial findings to clinical practice. Potential solutions to improve reporting include modification of submission guidelines, use of online appendices, and providing open access to trial protocols.

Pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in accordance with the licensed indication, based upon the evidence submission from Eli Lilly Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The majority of the efficacy evidence described in the manufacturer's submission is derived from a phase III open-label randomised controlled trial (RCT) known as the JMDB trial. The trial achieved its primary objective to demonstrate non-inferiority of pemetrexed/cisplatin to gemcitabine/cisplatin for overall survival in all patients with NSCLC. Because no other studies were found comparing pemetrexed/cisplatin with any other relevant comparator, additional efficacy evidence was presented from two phase III RCTs comparing gemcitabine/cisplatin with gemcitabine/carboplatin and docetaxel/cisplatin. The manufacturer's submission reported from its indirect comparisons' analysis that median overall survival and progression-free survival and tumour response rates were more favourable for pemetrexed/cisplatin than for any other comparator. The manufacturer did not identify any published cost-effectiveness analyses of pemetrexed for the first-line treatment of patients with NSCLC. Therefore economic evidence was derived solely from a de novo economic model developed by the manufacturer. A Markov model was developed to evaluate the cost-effectiveness of pemetrexed/cisplatin compared to gemcitabine/cisplatin, docetaxel/cisplatin and gemcitabine/carboplatin. The clinical data used in the economic evaluation were primarily generated from the JMDB trial, with additional data from the two further trials used in the indirect comparisons analysis. The ERG identified a series of problems with this economic model. As a result, three different versions of the model were submitted to NICE and considered by the ERG. The ICERs estimated by this final version of the model ranged from 8056 pounds to 33,065 pounds per QALY, depending on the comparator, the population and the application of a continuation rule. The ERG considered that the model required extensive modification and redesign, and should be subjected to thorough validation against the JMDB trial results. A full quality audit was also required as it was likely that further model inconsistencies may be present that had not yet been identified. The manufacturer subsequently included evidence in the form of three cost effectiveness analyses (two models and an 'in-trial' analysis), stating that a thorough validation process had been followed according to the NICE request. The very short time available to the ERG to consider the new evidence precluded a comprehensive assessment. Instead, the ERG chose to present a simple exploratory analysis combining its own survival projections with key cost estimates obtained from the JMDB trial individual patient data. Compared to gemcitabine, this resulted in ICERs ranging from 17,162 pounds to 30,142 pounds per QALY, depending on the patient population, the maximum number of cycles of chemotherapy and whether a cycle based efficacy adjustment was applied or not. The guidance issued by NICE in September 2009 states that pemetrexed in combination with cisplatin is recommended as an option for the first-line treatment of patients with locally advanced or metastatic NSCLC only if the histology of the tumour has been confirmed as adenocarcinoma or large-cell carcinoma.

Pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in accordance with the licensed indication, based upon the evidence submission from Eli Lilly Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The majority of the efficacy evidence described in the manufacturer’s submission is derived from a phase III open label randomised controlled trial (RCT) known as the JMDB trial. The trial achieved its primary objective to demonstrate non-inferiority of pemetrexed/cisplatin to gemcitabine/cisplatin for overall survival in all patients with NSCLC. Because no other studies were found comparing pemetrexed/cisplatin with any other relevant comparator, additional efficacy evidence was presented from two phase III RCTs comparing gemcitabine/cisplatin with gemcitabine/carboplatin and docetaxel/cisplatin. The manufacturer’s submission reported from its indirect comparisons’ analysis that median overall survival and progression-free survival and tumour response rates were more favourable for pemetrexed/cisplatin than for any other comparator. The manufacturer did not identify any published cost-effectiveness analyses of pemetrexed for the first-line treatment of patients with NSCLC. Therefore economic evidence was derived solely from a de novo economic model developed by the manufacturer. A Markov model was developed to evaluate the cost-effectiveness of pemetrexed/cisplatin compared to gemcitabine/cisplatin, docetaxel/cisplatin and gemcitabine/carboplatin. The clinical data used in the economic evaluation were primarily generated from the JMDB trial, with additional data from the two further trials used in the indirect comparisons analysis. The ERG identified series problems with this economic model. As a result, three different versions of the model were submitted to NICE and considered by the ERG. The ICERs estimated by this final version of the model ranged from £8056 to £33,065 per QALY, depending on the comparator, the population and the application of a continuation rule. The ERG considered that the model required extensive modification and redesign, and should be subjected to thorough validation against the JMDB trial results. A full quality audit was also required as it was likely that further model inconsistencies may be present that had not yet been identified. The manufacturer subsequently included evidence in the form of three cost effectiveness analyses (two models and an ‘in-trial’ analysis), stating that a thorough validation process had been followed according to the NICE request. The very short time available to the ERG to consider the new evidence precluded a comprehensive assessment. Instead, the ERG chose to present a simple exploratory analysis combining its own survival projections with key cost estimates obtained from the JMDB trial individual patient data. Compared to gemcitabine, this resulted in ICERs ranging from £17,162 to £30,142 per QALY, depending on the patient population, the maximum number of cycles of chemotherapy and whether a cycle based efficacy adjustment was applied or not. The guidance issued by NICE in September 2009 states that pemetrexed in combination with cisplatin is recommended as an option for the first-line treatment of patients with locally advanced or metastatic NSCLC only if the histology of the tumour has been confirmed as adenocarcinoma or large-cell carcinoma.

Fatigue strength and failure mechanism for the aluminium wrought alloy EN AW 6056 in the VHCF-region and influence of notches and compressive residual stresses

The fatigue strength and the transition of failure mechanism from the high cycle fatigue (HCF) to the very high cycle fatigue regime (VHCF) for EN AW 6056 were investigated at mechanically polished, smooth specimens. Fatigue tests were conducted with a servohydraulic testing machine and a resonant frequency machine at room temperature. Tests run up to a maximum number of cycles N=2⋅108.The results reveal that the fatigue strength decreases with increasing number of cycles, which is known for materials with facecentred cubic lattice. In the very high cycle regime the crack initiation sites of the smooth specimens were internal. Fracture surface and microstructure of the crack initiation sites were investigated by means of scanning electron microscope (SEM), energy dispersive X-ray analysis (EDX), electron back scatter diffraction analysis (EBSD) and metallographic methods. The influence of notches was investigated at slightly notched (Kt=1.75) and sharp notched (screws M10, Kt=4.7) specimens. The influence of compressive residual stresses was investigated by a comparison of precision-turned and shot-peened, slightly notched specimens as well as screws of with thread rolling before heat treatment and thread rolling after heat treatment. The fatigue strength of the specimens without compressive residual stresses decreases with increasing number of cycles. The fatigue strength of the specimens with compressive residual stresses shows a horizontal SN-curve after a point of deflection. The crack initiation sites of the notched specimens were always at the root of the notch independent of the compressive residual stresses and the number of cycles.

A Randomized Phase 2 Study of Sapacitabine, An Oral Nucleoside Analogue, in Older Patients with Myelodysplastic Syndrome (MDS) Refractory to Hypomethylating Agents.

Abstract 1758Poster Board I-784 IntroductionSapacitabine is a novel nucleoside analogue with a unique ability to cause irreparable single-strand DNA breaks and induce G2 cell cycle arrest. It is orally administered and has demonstrated promising anti-leukemic activity against relapsed or refractory AML and MDS in a phase 1 trial. We are conducting a multi-center, open-label, randomized phase 2 study to evaluate 3 dose regimens of this drug in older patients with MDS refractory to hypomethylating agents. The primary objective is to evaluate 1-year survival rate. The study uses a selection design to identify a dose regimen which produces a better 1-year survival rate in the event that all three dose regimens are active. There is an early stopping rule for excessive toxicity. The planned sample size consists of 60 patients or 20 patients in each arm. Patients and MethodsEligible patients must be ≥60 years with MDS and an IPSS score of intermediate -2 or high - risk who have been previously treated with hypomethylating agents, ECOG 0-2, creatinine '1.5 x ULN, total bilirubin or direct bilirubin '1.5 x ULN and ALT '2.5 x ULN or '5 x ULN if the liver is involved by leukemic blasts. Patients were randomized 1:1:1 to receive one of the 3 dose regimens: 200 mg b.i.d. x 7 days every 3-4 weeks (Arm A), 300 mg b.i.d. x 7 days every 3-4 weeks (Arm B), or 400 mg b.i.d. x 3 days per week x 2 weeks every 3-4 weeks (Arm C). There is no limit on the maximum number of cycles. The primary efficacy endpoint is 1-year survival. Secondary efficacy endpoints include the rate of CR, CRp, PR, CRi or hematological improvement (HI) and their corresponding response durations. ResultsAs of August 2009, 39 older patients with MDS refractory to hypomethylating agents have been treated and had ≥ 30 days of follow-up. There are 13 patients on each arm. Median age was 73 and 79% of patients were 70 years or older. Baseline bone marrow contained 5-10% blasts in 20 patients (51%), 11-20% blasts in 16 patients (41%) and 21-30% blasts in 2 patients (5%). The median number of cycles was 2 and 33% of patients received ≥ 4 cycles. Overall response rate is 23% (1 CR and 8 major HIs): 23% (Arm A), 38% (Arm B) and 8% (Arm C). Median time to response is 1-2 cycles (range 1-5). One death occurred within 30 days of randomization and the death was considered to be unrelated to sapacitabine. According to interim safety data, common adverse events (all grades, regardless of causality) included fatigue, nausea, diarrhea, constipation, anemia, neutropenia and alopecia, most of which were mild to moderate in intensity. ConclusionSapacitabine appears to be safe across all 3 dose regimens. Based on interim data, the highest overall response rate was observed on the 7-day high dose regimen (Arm B). Updated data will be presented at the meeting. DisclosuresChiao:Cyclacel: Employment.

A Randomized Phase 2 Study of Sapacitabine, An Oral Nucleoside Analogue, in Elderly Patients with AML Previously Untreated or in First Relapse.

Abstract 1061Poster Board I-83 Introduction:Sapacitabine is a novel nucleoside analogue with a unique ability to cause irreparable single-strand DNA breaks and induce G2 cell cycle arrest. It is orally administered and has demonstrated promising anti-leukemic activity against relapsed or refractory AML and MDS in a phase 1 trial. We are conducting a multi-center, open-label, randomized phase 2 study to evaluate 3 dose regimens of this drug in elderly AML. The primary objective is to evaluate 1-year survival rate. The study uses a selection design to identify a dose regimen which produces a better 1-year survival rate in the event that all three dose regimens are active. The planned sample size consists of 60 patients or 20 patients in each arm. The study also uses a Bayesian continuous monitoring rule to stop accrual in one or more arms of the study in the event that a dose regimen does not have a sufficient number of responses. Patients and Methods:Eligible patients must be ≥70 years with AML previously untreated or in first relapse, ECOG 0-2, creatinine ≤ 1.5 x ULN, total bilirubin or direct bilirubin ≤ 1.5 x ULN and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if the liver is involved by leukemic blasts. Patients were randomized 1:1:1 to receive one of the 3 dose regimens: 200 mg b.i.d. x 7 days every 3-4 weeks (Arm A), 300 mg b.i.d. x 7 days every 3-4 weeks (Arm B), or 400 mg b.i.d. x 3 days per week x 2 weeks every 3-4 weeks (Arm C). There is no limit on the maximum number of cycles. The primary efficacy endpoint is 1-year survival. Secondary efficacy endpoints include the rate of CR, CRp, PR, CRi or hematological improvement (HI) and their corresponding response durations. Results:Between December 2007 and October 2008, 60 elderly patients with AML were enrolled and treated. Median age was 77 and 35% of patients were 80 years or older. Fifty-one patients had previously untreated AML and 9 patients had AML in 1st relapse. The majority of the patients (87%) had intermediate/unfavorable risk karyotypes and 45% of AML were preceded by an antecedent hematological disease (AHD). As of August 2009, 9 patients are still on study. The median number of cycles was 3 and 18 patients (30%) received ≥ 6 cycles. Four patients (7%) discontinued treatment for unacceptable toxicity. The overall response rate is 45% on Arm A (10% CR, 35% PR/major HI), 25% on Arm B (10% CR/CRp, 15% PR/major HI), 35% on Arm C (25% CR, 10% major HI). Median time to response is 3 cycles (range 1-9). Eight deaths of all causes occurred within 30 days of randomization and one death was considered to be possibly related to sapacitabine. According to interim safety data, common adverse events (all grades, regardless of causality) included fatigue, nausea, diarrhea, anemia, febrile neutropenia, thrombocytopenia and peripheral edema, most of which were mild to moderate in intensity. Conclusion:Sapacitabine is safe and active across all 3 dose regiments with the highest CR rate observed on the 3-day dose regimen (Arm C). Mature 1-year survival data will be presented at the meeting. Disclosures:Kantarjian:Cyclacel, Inc.: Research Funding. Garcia-Manero:Cyclacel, Inc.: Research Funding. Chiao:Cyclacel, Inc.: Employment, Equity Ownership.

Dacetuzumab (SGN-40), Lenalidomide, and Weekly Dexamethasone in Relapsed or Refractory Multiple Myeloma: Multiple Responses Observed in a Phase 1b Study.

Abstract 2870Poster Board II-846 Background:Dacetuzumab (SGN-40) is a humanized monoclonal antibody that targets CD40. In prior phase 1 studies, antitumor activity was demonstrated with dacetuzumab monotherapy in patients with non-Hodgkin lymphoma and stabilization of disease was noted in multiple myeloma (MM) patients. Preclinical data demonstrate that the addition of lenalidomide to dacetuzumab markedly enhances dacetuzumab-mediated ADCC and apoptosis in both MM cell lines and patient isolates through modulation of NK cell activity. Methods:A phase 1b, dose-escalation study of dacetuzumab, lenalidomide, and low-dose dexamethasone has been initiated in patients with relapsed or refractory MM. Patients were enrolled in a 3+3 dose-escalation scheme and were given cohort-specific doses of weekly IV dacetuzumab (4, 8, or 12 mg/kg) in addition to oral lenalidomide (25 mg, Days 1-21 every 28 days), and weekly oral dexamethasone (40 mg). At the conclusion of dose escalation, the highest tolerated dose combination was used to treat an expansion cohort, approximately half of whom were lenalidomide-naïve. The maximum number of cycles permitted was 8, or 2 cycles beyond a complete response (CR). Results:Thirty-six patients from 8 centers were enrolled and treated, 15 patients in 3 dose-escalation cohorts and 21 patients in the expansion cohort at the 12 mg/kg dacetuzumab dose level. The median age of patients was 65 years (range 48-83) with a median of 3.4 years since diagnosis (range 1-11); patients were heavily pretreated (median of 4 prior systemic regimens [range 2-14]). The median number of cycles received was 4 (range 1-8), although 14 patients remain on treatment. The most common adverse events (AEs) in the study were fatigue (47%), neutropenia (28%), thrombocytopenia (25%), diarrhea (22%), constipation (19%), and headache (19%), the majority of which were Grade 1 or 2 in severity. Two patients discontinued treatment due to dose-limiting toxicity (DLT) during Cycle 1: one patient developed Grade 3 herpes zoster (4 mg/kg); a second patient developed Grade 4 renal failure requiring dialysis (12 mg/kg). This patient had IgA myeloma with a rising M-protein and deteriorating kidney function at study entry; the patient's renal function eventually improved and dialysis was no longer required. Another patient discontinued treatment due to a serious AE that was not considered a DLT (tumor lysis syndrome). Of 33 patients who have had Investigator-assessed response evaluations according to the European Group for Bone Marrow and Transplantation criteria, 13 patients (39%) achieved an objective response (1 CR, 12 partial responses [PR]); other responses were 4 (12%) minimal responses (MR), 10 patients (30%) had stable disease (SD), 2 patients (6%) had progressive disease (PD), and 4 patients (12%) were not evaluable. Responses that occurred among lenalidomide-naïve patients (n=18) were 1 CR, 9 PR, 1 MR, 3 SD, 2 PD, and 2 not evaluable. Among patients who have previously received lenalidomide (n=18), the responses were 3 PR, 3 MR, 7 SD, and 2 not evaluable; additionally, 3 patients who are receiving treatment have not yet been assessed for response. Conclusion:The combination regimen of dacetuzumab, lenalidomide, and low-dose dexamethasone was generally well tolerated at all doses studied. Evidence of anti-myeloma activity with this combination is encouraging as antitumor activity was observed in patients with MM who have previously received lenalidomide as well as lenalidomide-naïve patients. Disclosures:Agura:Seattle Genetics, Inc.: Research Funding. Off Label Use: Dacetuzumab is an investigational agent. Niesvizky:Proteolix: Research Funding, data monitoring committee; Seattle Genetics, Inc: Research Funding; Millenium: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau. Matous:Seattle Genetics, Inc.: Research Funding; Celgene: Honoraria, Speakers Bureau. Munshi:Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics, Inc.: Research Funding. Hussein:Seattle Genetics, Inc.: Research Funding. Parameswaran:Seattle Genetics, Inc.: Research Funding. Tarantolo:Seattle Genetics, Inc.: Research Funding. Whiting:Seattle Genetics, Inc.: Employment, Equity Ownership. Drachman:Seattle Genetics, Inc.: Employment, Equity Ownership. Zonder:Pfizer: Consultancy; Seattle Genetics, Inc.: Research Funding; Millennium: Research Funding; Amgen: Consultancy; Celgene: Speakers Bureau.

On the maximum number of cycles in outerplanar and series-parallel graphs

Abstract Let c ( n ) be the maximum number of cycles in an outerplanar graph with n vertices. We show that lim c ( n ) 1 / n exists and equals β = 1.502837 … , where β is a constant related to the recurrence x n + 1 = 1 + x n 2 , x 0 = 1 . The same result holds for the larger class of series-parallel graphs.

A randomized trial of gemcitabine (G) versus G plus cisplatin in chemotherapy-naive advanced pancreatic adenocarcinoma: The GIP-1 (Gruppo Italiano Pancreas— GOIM/GISCAD/GOIRC) study

4504 Background: Single-agent gemcitabine (G) remains standard treatment for advanced pancreatic adenocarcinoma (APC). The GIP-1 randomized phase III trial (clinicaltrials.gov ID NCT00813696 ) was performed to compare the combination of cisplatin (P) and G vs. G alone as 1st-line treatment. Methods: Patients (pts) with locally advanced and/or metastatic pancreatic adenocarcinoma, age 18–75, Karnofsky Performance Status (KPS) ≥50, were randomized to receive G (arm A) or G+P (arm B). In arm A, G was administered at 1000 mg/m2 weekly for 7 consecutive wks, and, after a 2-week rest, on day 1, 8, 15 every 4 wks. In Arm B, P 25 mg/m2 weekly (with the exception of day 22) was added to G, same dose used in Arm A (Colucci et al, Cancer 2002; 94:902–10). No maximum number of cycles was planned. Primary endpoint was overall survival (OS). Clinical benefit (CB), objective response rate (ORR), progression-free survival (PFS), toxicity and quality of life were secondary endpoints. To have 80% power of detecting a 0.74 Hazard Ratio (HR) of death (corresponding to increase in median OS from 4.8 to 6.5 months, with bilateral alpha=0.05, 400 pts were planned and 355 deaths were required for final analysis. Results: From April 2002 to April 2007, 400 pts were enrolled (A:199, B; 201) in 46 Italian Institutions. Median age was 63 yrs (range 35–75), 59% were males, 84% stage IV, 83% KPS≥80. After a median follow-up of 38.2 months and 357 deaths, median OS was 8.3 vs 7.2 months in arm A and B, respectively (HR 1.10, 95% CI 0.89–1.35, p=0.38). Median PFS was 3.9 vs 3.8 months in arm A and B, respectively (HR 0.97, 95% CI 0.80–1.19, p=0.80). ORR was 10.1% in arm A and 12.9% in B (p=0.37). CB response was experienced by 23.0% and 15.1% (Arm A vs B, p=0.057). Patients assigned to combination arm experienced more anaemia (all grades: 50% vs 39%, G3: 5% vs 1%), more neutropenia (all grades: 44% vs 36%, G3&amp;4: 25% vs 14%) and more thrombocytopenia (all grades: 57% vs 29%, G3&amp;4: 16% vs 5%). No relevant differences were seen in non-haematological toxicity. Conclusions: Weekly combination of P and G, compared to single-agent G as 1st-line treatment of APC, failed to demonstrate any improvement in OS, PFS, ORR and clinical benefit. No significant financial relationships to disclose.

Fatigue behaviour of dental composite materials

Objective The intent of the project was to evaluate the fatigue behavior of particle and fiber filled dental composites that are fabricated either directly or indirectly using a notched specimen with respect to the number of cycles until failure. Methods The materials were five dental composites, three normally cured in the oral cavity (Restolux, Renew and Filtek Supreme), direct processing, and two laboratory produced (BelleGlass, and Tescera), indirect processing. The specimens were 3 mm × 3 mm × 25 mm bars with a 0.75 or 1.0 mm notch in the mid-span of the bars, polished with 320 grit SiC paper and aged for 6 months in air, distilled water, artificial saliva, and a 50/50 mixture of ethanol and distilled water. Testing was performed with a stress mean range of 5–49 MPa, the maximum number of cycles was 100,000, and the number of cycles to failure was recorded. Results For the specimens that failed, BelleGlass, Restolux, and Tescera were able to withstand a higher cyclic loaded stress than Renew and Filtek. The 50/50 by volume mixture of water and ethanol resulted in the lowest resistance to fatigue for all materials. Conclusions Of the dental composite materials investigated, the indirect processed and those with large particle fillers (higher weight percent filler) had better cyclic fatigue resistance than micro- and nano-particle fillers (lower weight percent filler).

Fatigue Behaviors of Ultra Fine Wires of &amp;beta;-Type and &amp;alpha;-Type Titanium Alloys

Fatigue behaviors of ultra fine wires of � -type Ti-14Mo-3Nb-1.5Zr alloy and � -type Ti-10Zr alloy and � -type CP (commercially pure) titanium with diameters in the range of 35–100 mm were investigated by rotating-bending fatigue testing in 1 mass% lactic acid solution maintained at 310 K. The maximum number of cycles during fatigue testing was 10 7 . The � -type Ti-14Mo-3Nb-1.5Zr alloy wires showed a clear fatigue limit. On the other hand, the � -type Ti-10Zr alloy wire and � -type CP titanium wire did not show a clear fatigue limit, and their fatigue strengths gradually decreased with decreasing maximum bending stress. The fatigue limit of a � -type Ti-14Mo-3Nb-1.5Zr alloy wire with a polished surface was greater than 50% of its tensile strength, while the fatigue limits of titanium wires with as-drawn surfaces were less than 50% of their tensile strengths. Surface defects that were introduced during the cold drawing process of the wires might act as crack origins of the fatigue fracture. Therefore, surface polishing is an effective technique for improving fatigue properties of titanium wires. The elution of metallic ions from the wires into the 1 mass% lactic acid solution was suppressed at a very low level during fatigue testing of all the investigated titanium wires. [doi:10.2320/matertrans.MF200920]

An Extremal Characterization of Projective Planes

In this article, we prove that amongst all $n$ by $n$ bipartite graphs of girth at least six, where $n = q^2 + q + 1 \ge 157$, the incidence graph of a projective plane of order $q$, when it exists, has the maximum number of cycles of length eight. This characterizes projective planes as the partial planes with the maximum number of quadrilaterals.

Electropolymerized tyrosine-based thin films: Selective cell binding via peptide recognition to novel electropolymerized biomimetic tyrosine RGDY films

We have created thin films by cyclic voltammetry (CV) electropolymerizations of the following phenolic functional group-based monomers: phenol; tyrosineamide; the tetrapeptide RGDY-containing the integrin membrane adhesion protein recognition tripeptide RGD; RDGY, a nonsense control tetrapeptide; and 1:3 mixtures of tyrosineamide with the two tetrapeptide monomers. The film formation process and description of the film properties were obtained by repetitive CV cycling using the oscillating quartz frequency shift, Δ f, and motional resistance shift, Δ R, parameters obtained with the electrochemical quartz crystal microbalance technique. Only the poly(phenol) film exhibited close chain packing-based self-limiting behavior, where all film synthesis ceased after approximately 7 CV cycles. All other films continued to form by electropolymerization with successive CV cycles out to the maximum cycle number (30 cycles) we measured. All of the films exhibited little energy dissipation behavior. Using the quartz crystal microbalance, we next compared the time course of cell attachment with the washed films and demonstrated that cells bound best to films in the following order: RGDY sense peptide:tyrosineamide films > RDGY nonsense peptide:tyrosineamide films = tyrosineamide films > phenol films. Cell enumeration after washing and trypsinization revealed firm protein-based cell attachment to the underlying extracellular matrix for the RGDY-containing films. These sense peptide films bound and retained two- to fivefold as many cells as the other films, with cells exhibiting a normal morphology. These results suggest the operation of specific cell attachment to the electropolymerized films via the RGD binding site for cellular integrin membrane proteins. The electropolymerization method we studied here forms a cassette system for creating electropolymerized films tailored to specific attachment of different cell types by varying the electropolymerized Y(tyrosine)-containing recognition peptide.

Heating systems with PLC and frequency control

In this work, medium capacity controlled heating system is designed and constructed. The programming method of control of heating process is achieved by means of integrated programmable logic controller (PLC) and frequency inverter (FI). The PLC main function is to determine the required temperatures levels and the related time intervals of the heating hold time in the furnace. FI is used to control the dynamic change of temperature between various operating points. The designed system shows the capability for full control of temperature from zero to maximum for any required range of time in case of increasing or decreasing the temperature. All variables of the system will be changed gradually until reaching their needed working points. An experimental study was performed to investigate the effect of tempering temperature and tempering time on hardness and fatigue resistance of 0.4% carbon steel. It was found that increasing tempering temperature above 550 °C or tempering time decreases the hardness of the material. It was also found that there is a maximum number of cycles to which the specimen can survive what ever the applied load was.