bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic steering controllers for general lane-following manoeuvres of passenger cars using 2-DOF robust control synthesis
Authors: You Sam-Sang , Jeong Seok-Kwon
Published: September 2004

This paper deals with the modelling and robust control synthesis of intelligent vehicles for general lateral motion in intelligent transportation system applications. The lateral vehicle dynamics for general lane following are firstly derived in a unified framework. Based on a coprime factor plant description, the two-degree-of freedom based H1 loop-shaping control scheme is presented for lane keeping and changing manoeuvres simultaneously. The resulting robust controller is generally of high order and has to be reduced for real implementation. Also, the reduced-order controller is evaluated in both the frequency- and the time-domain analysis. Finally, it is found that the proposed automatic steering controller provides robust performance and stability for a given vehicle manoeuvring in the presence of parameter variations of vehicles.
Investigation of an inertial-sensor-based dynamic position measurement system for a parallel kinematic machine
Authors: Gao Jian , Webb Phil , Gindy Nabil
Published: September 2004

The key to the positional accuracy of a Parallel Kinematic Machine (PKM) is the precision to which the lengths of the individual parallel links (or struts) can be measured. The strut length can be measured to a high degree of precision using a laser interferometer but this is expensive. Alternatively, encoders may be used to measure the relative change in length of the strut but they can only record ball screw or motor rotation, and cannot detect any deformations that may occur within the machine’s structure. In addition, only limited information on any dynamic disturbances such as vibration can be obtained. To obtain this type of data, displacement should be directly measured at the end of the strut. The use of inertial sensors offers a possible solution since they are self-contained, relatively low cost and can be easily mounted on the machine structure. However, an inherent limitation of inertial systems is the growth, with time, of errors in measured velocity and position; in the system described within this paper, they are corrected by using an external reference measurement and Kalman filtering. Through the integration of the two measurement systems, a velocity profile containing improved dynamic information can be calculated. The key steps required for the integration of the inertial and encoder measurement systems are introduced, and include the formulation of a system and measurement model and Kalman filter estimation and testing. In order to investigate the feasibility of the proposed measurement system, it was evaluated using a single PKM strut. The experimental results are presented and analysed.
Primitive maximum-length sequences and pseudo-random signals
Authors: Barker H. Anthony
Published: September 2004

Primitive maximum-length sequences in a Galois field GF(q) are defined as the simplest maximum-length sequences in the field, and their nature and properties are demonstrated. Primitive pseudo-random signals are then defined as signals generated from primitive maximum-length sequences by converting the field elements into signal levels. It is shown that the harmonic properties of a primitive pseudo-random signal define the harmonic properties of all pseudo-random signals generated from the same field with the same field element conversions. This leads to a procedure for designing pseudo-random signals with desirable properties for system identification that simply involves designing primitive pseudo-random signals with the same properties. The design procedure is described, and illustrated by primitive maximum-length sequences and pseudo-random signals in the field GF(7).
Optimization of legged robot locomotion by control of foot-force distribution
Authors: Jiang W. Y. , Liu A. M. , Howard D.
Published: September 2004

The contribution of this paper is the introduction of three new pseudo-inverse formulations for the real-time control of foot-force distribution in multi-legged walking machines. Three alternative locomotion performance objectives are proposed for the purpose of optimizing the foot-force distribution. An exhaustive search method has been used to obtain truly optimal results, which are then used for comparison with the results obtained using suboptimal pseudo-inverse formulations that are suitable for real-time control. Simulation results show that, by using the appropriate pseudo-inverse formulation, a good approximation to the corresponding optimal foot-force distribution can be obtained. Furthermore, it is clear that the friction duty factor formulation provides an excellent real-time solution for minimizing the risk of foot-slip.
Link between high-gain observer-based and parity space residuals for FDI
Authors: Christophe Cyrille , Cocquempot Vincent , Jiang Bin
Published: September 2004

This paper deals with residual generation methods for nonlinear model-based fault detection and isolation (FDI) systems. More specifically, a differential relationship between nonlinear parity space residuals (based on analytical redundancy relations) and high-gain observer-based residuals is emphasized. The first part of this paper presents the nonlinear affine state space model, which is considered to generate residuals in the following. In order to design the high-gain observer, a nonlinear transformation is used to put the model under its observable canonical form (OCF). The two residual generation approaches are detailed in the second part. The result of the paper is then established: we express explicitly a differential relationship between the two residuals and so extend in a more general framework the well known result that was established for linear and linearizable systems by input/output injection. A model of a series DC motor is considered to illustrate the theoretical result and simulations results are presented.
Quality governance for sustainable development?
Authors: Mc Lennan Anne , Ngoma Wendy Yolisa
Published: September 2004

The meanings of public administration, inclusive governance and sustainable development in a globalized context are reviewed in order to explore how public administration can ensure sustainable development in the contexts of limited resources, poverty and inequality. The key argument is that sustainable development will remain an imaginary exercise unless attention is given to building institutional capacity. The discussion moves beyond an examination of the role of the state in facilitating sustainable development to explore options for service delivery that address poverty and exclusion. Of key importance in exploring the theme of quality governance for sustainable development is the role of government in supporting institutions and building institutional capacity. This strategy would need to be targeted not simply at the institutions of the state - schools, hospitals and agencies - but also at the institutions of civil society. A reinvestment in public institutions may ensure sustainability in the context of limited resources.
Measuring performance under a landscape approach to biodiversity conservation: the case of USAID/Madagascar
Authors: Medley Kimberly E.
Published: September 2004

Under a ‘landscape approach’ to biodiversity conservation, USAID/Madagascar integrates by design concerns for forest resources and humans in five target ecoregions. This paper examines relationships between its strategic framework and how the mission reports results from development interventions between 1998 and 2002 in protected areas, multipurpose forests and agricultural lands. Development activities focused on expanding parks and reducing negative impacts by local communities. In contrast, a proposal for ecological monitoring provides opportunities for information sharing and consultation among stakeholders about biodiversity conditions under different land uses. The study recommends strengthening incentives for community participation by measuring positive change across human-modified landscapes.
Early Hospital Discharge Followed by Outpatient Management Versus Continued Hospitalization of Children With Cancer, Fever, and Neutropenia at Low Risk for Invasive Bacterial Infection
Authors: Santolaya María E. , Alvarez Ana M. , Avilés Carmen L. , Becker Ana , Cofré José , Cumsille Miguel A. , O'Ryan Miguel L. , Payá Ernesto , Salgado Carmen , Silva Pamela , Tordecilla Juan , Varas Mónica , Villarroel Milena , Viviani Tamara , Zubieta Marcela
Published: September 2004

Purpose

To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection (IBI).

Patients and Methods

Children presenting with febrile neutropenia at six hospitals in Santiago, Chile, were categorized as high or low risk for IBI. Low-risk children were randomly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution. Outcome and cost were determined for each episode and compared between both groups using predefined definitions and questionnaires.

Results

A total of 161 (41%) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk, of which 149 were randomly assigned to ambulatory (n = 78) or hospital-based (n = 71) treatment. In both groups, mean age (ambulatory management, 55 months; hospital-based management, 66 months), sex, and type of cancer were similar. Outcome was favorable in 74 (95%) of 78 ambulatory-treated children and 67 (94%) of 71 hospital-treated children (P = NS). Mean cost of an episode was US $638 (95% CI, $572 to $703) and US $903 (95% CI, $781 to $1,025) for the ambulatory and hospital-based groups, respectively (P = .003).

Conclusion

For children with febrile neutropenia at low risk for IBI, ambulatory management is safe and significantly cost saving compared with standard hospitalized therapy.
Systematic Review of the Staging Performance of18F-Fluorodeoxyglucose Positron Emission Tomography in Esophageal Cancer
Authors: van Westreenen H.L. , Westerterp M. , Bossuyt P.M.M. , Pruim J. , Sloof G.W. , van Lanschot J.J.B. , Groen H. , Plukker J.Th.M.
Published: September 2004

Purpose

Despite the increasing number of publications concerning18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for staging of esophageal cancer and the increasing availability of this novel diagnostic modality, its exact role in preoperative staging of these tumors is still unknown. The aim of this study was to systematically review the literature regarding the diagnostic performance of FDG-PET in preoperative staging of patients with esophageal cancer, and to calculate summary estimates of its sensitivity and specificity.

Methods

The databases of PubMed, Embase, and Cochrane were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed.

Results

Twelve studies met the inclusion criteria. The studies had several design deficiencies. Pooled sensitivity and specificity for the detection of locoregional metastases were 0.51 (95% CI, 0.34 to 0.69) and 0.84 (95% CI, 0.76 to 0.91), respectively. For distant metastases, pooled sensitivity and specificity were 0.67 (95% CI, 0.58 to 0.76) and 0.97 (95% CI, 0.90 to 1.0), respectively.

Conclusion

FDG-PET showed moderate sensitivity and specificity for the detection of locoregional metastases, and reasonable sensitivity and specificity in detection of distant lymphatic and hematogenous metastases.
Impact of the Percentage of Positive Prostate Cores on Prostate Cancer–Specific Mortality for Patients With Low or Favorable Intermediate-Risk Disease
Authors: D'Amico Anthony V. , Renshaw Andrew A. , Cote Kerri , Hurwitz Mark , Beard Clair , Loffredo Marian , Chen Ming-Hui
Published: September 2004

Purpose

We investigated whether pretreatment factors predicted time to prostate cancer–specific mortality (PCSM) after conventional-dose and conformal radiation therapy (CRT).

Patients and Methods

Between 1988 and 2002, 421 patients with low (prostate-specific antigen [PSA] level ≤ 10 ng/mL and biopsy Gleason score ≤ 6) or favorable intermediate-risk (PSA > 10 to 15 ng/mL or biopsy Gleason score 3 + 4, but not both factors) disease underwent CRT (median dose, 70.4 Gy). Cox regression multivariable analysis was performed to determine whether the PSA level, Gleason score, T category, or the percentage of positive cores (% PC) predicted time to PCSM after CRT. After a median follow-up of 4.5 years, 117 (28%) patients have died.

Results

The % PC was the only significant predictor (Cox P ≤ .03). The relative risk of PCSM after CRT for patients with ≥ 50% as compared with less than 50% PC was 10.4 (95% CI, 1.2 to 87; Cox P = .03), 6.1 (95% CI, 1.3 to 28.6; Cox P = .02), and 12.5 (95% CI, 1.5 to 107; Cox P = .02) in men with a PSA ≤ 10 and Gleason score ≤ 6, PSA ≤ 10 and Gleason score ≤ 7, and PSA ≤ 15 and Gleason score ≤ 6, respectively. By 5 years after CRT, 5% to 9% compared with less than 1% (log-rank P ≤ .01) of these patients experienced PCSM if they had ≥ 50% compared with less than 50% PC, respectively.

Conclusion

CRT dose-escalation techniques, the addition of hormonal therapy, or both should be considered in the management of patients with low or favorable intermediate-risk disease and ≥ 50% PC.
Randomized Comparison of Power Doppler Ultrasound-Directed Excisional Biopsy With Standard Excisional Biopsy for the Characterization of Lymphadenopathies in Patients With Suspected Lymphoma
Authors: Picardi Marco , Gennarelli Nicola , Ciancia Rosanna , De Renzo Amalia , Gargiulo Giovanna , Ciancia Giuseppe , Sparano Lucianna , Zeppa Pio , Martinelli Vincenzo , Pettinato Guido , Lobello Roberto , Pane Fabrizio , Rotoli Bruno
Published: September 2004

Purpose

The sensitivity of lymph node excisional biopsy requires validation. Power Doppler ultrasound (US) helps predict the malignant status of lymphadenopathies. We used power Doppler US to select for biopsy the lymph node most suspected of malignancy.

Patients and Methods

One hundred fifty-two patients having lymphadenopathies with clinical suspicion of lymphoma were divided into two well-matched groups and randomly assigned to undergo either standard or power Doppler US-directed lymph node excisional biopsy.

Results

Histology showed a malignancy in 64% of patients in the standard group (lymphoma, 49 patients; carcinoma, two patients) and in 87% of patients in the US-assisted group (lymphoma, 62 patients; carcinoma, one patient). There were significantly fewer biopsy-related complications in the assisted group than in the standard group. During the follow-up of the patients with lymph nodes reported as being reactive, 14 of 29 patients in the standard group were rebiopsied and were found to have lymphoma (13 patients) or carcinoma at the subsequent lymph node histology, whereas none of the patients in the assisted group (nine patients) required a second biopsy. Thus, biopsy provided false-negative results for malignancy in 21% of patients affected by lymphoma in the standard group and never in the assisted group (P < .01).

Conclusion

Power Doppler US is an accurate tool for screening lymphadenopathies to be removed by excisional biopsy in patients with suspected lymphoma.
Effect of Doxorubicin Plus Cyclophosphamide on Left Ventricular Ejection Fraction in Patients With Breast Cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial
Authors: Perez Edith A. , Suman Vera J. , Davidson Nancy E. , Kaufman Peter A. , Martino Silvana , Dakhil Shaker R. , Ingle James N. , Rodeheffer Richard J. , Gersh Bernard J. , Jaffe Allan S.
Published: September 2004

Purpose

To evaluate changes in left ventricular ejection fraction (LVEF) after four cycles of adjuvant doxorubicin plus cyclophosphamide (AC) in women with human epidermal growth factor receptor 2–positive (node-positive or node-negative) breast cancer enrolled onto the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial.

Patients and Methods

Patients were randomly assigned to receive standard doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) every 3 weeks for four cycles followed by (1) weekly paclitaxel for 12 weeks; (2) weekly paclitaxel for 12 weeks, then weekly trastuzumab for 52 weeks; or (3) weekly paclitaxel plus trastuzumab for 12 weeks, then weekly trastuzumab for 40 weeks. LVEF was monitored before and after AC.

Results

Of the 1,576 eligible patients who completed AC, 1,458 had pre- and post-AC LVEF measurements taken using the same methodology (multiple-gated acquisition in 1,153 patients and echocardiogram in 305 patients). Among these 1,458 patients, 745 (51.1%) had ≤ 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had ≤ 15% decrease in LVEF and LVEF that decreased to or below the LLN; and 37 patients (2.5%) had an LVEF decrease of more than 15%. There was grade 2 LVEF toxicity in 96 (6.6%) of the 1,458 patients.

Conclusion

Standard AC chemotherapy is associated with frequent decreases in LVEF, which are noted when measured 3 weeks after completion of the fourth cycle. Patients are being observed to determine the long-term significance of this and the potential impact on subsequent treatment options.
Biology of Gastrointestinal Stromal Tumors
Authors: Corless Christopher L. , Fletcher Jonathan A. , Heinrich Michael C.
Published: September 2004

Once a poorly defined pathologic oddity, in recent years, gastrointestinal stromal tumor (GIST) has emerged as a distinct oncogenetic entity that is now center stage in clinical trials of kinase-targeted therapies. This review charts the rapid progress that has established GIST as a model for understanding the role of oncogenic kinase mutations in human tumorigenesis. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT tyrosine kinase. In a series of 322 GISTs (including 140 previously published cases) studied by the authors in detail, mutations in the KIT gene occurred with decreasing frequency in exons 11 (66.1%), 9 (13%), 13 (1.2%), and 17 (0.6%). In the same series, a subset of tumors had mutations in the KIT-related kinase gene PDGF receptor alpha (PDGFRA), which occurred in either exon 18 (5.6%) or 12 (1.5%). The remainder of GISTs (12%) were wild type for both KIT and PDGFRA. Comparative studies of KIT-mutant, PDGFRA-mutant, and wild-type GISTs indicate that there are many similarities between these groups of tumors but also important differences. In particular, the responsiveness of GISTs to treatment with the kinase inhibitor imatinib varies substantially depending on the exonic location of the KIT or PDGFRA mutation. Given these differences, which have implications both for the diagnosis and treatment of GISTs, we propose a molecular-based classification of GIST. Recent studies of familial GIST, pediatric GIST, and variant forms of GIST related to Carney's triad and neurofibromatosis type 1 are discussed in relationship to this molecular classification. In addition, the role of mutation screening in KIT and PDGFRA as a diagnostic and prognostic aid is emphasized in this review.
Residual Tumor Resection After High-Dose Chemotherapy in Patients With Relapsed or Refractory Germ Cell Cancer
Authors: Rick O. , Bokemeyer C. , Weinknecht S. , Schirren J. , Pottek T. , Hartmann J.T. , Braun T. , Rachud B. , Weißbach L. , Hartmann M. , Siegert W. , Beyer J.
Published: September 2004

Purpose

To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT).

Patients and Methods

Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment.

Results

Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis.

Conclusion

Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.
Deleted in Colon Cancer Protein Expression in Colorectal Cancer Metastases: A Major Predictor of Survival in Patients With Unresectable Metastatic Disease Receiving Palliative Fluorouracil-Based Chemotherapy
Authors: Aschele Carlo , Debernardis Domizia , Lonardi Sara , Bandelloni Roberto , Casazza Stefania , Monfardini Silvio , Gallo Luigi
Published: September 2004

Purpose

To determine whether deleted in colon cancer (DCC) protein expression in colorectal cancer (CRC) metastases could predict outcome to palliative fluorouracil (FU)-based chemotherapy and to assess whether it is similar to that observed in the corresponding primary tumors.

Patients and Methods

DCC protein expression was assessed immunohistochemically on archival specimens of CRC metastases from 42 patients homogeneously treated by methotrexate-modulated bolus FU alternated to 6-S-leucovorin–modulated infused FU and was retrospectively correlated with patient characteristics and clinical outcome. In a subset analysis, DCC immunoreactivity was compared between metastatic CRC and the corresponding primary tumors and regional lymph node metastases.

Results

Positive immunoreactivity for DCC was found in 45% of patients. Eighteen (78%) of 23 patients for whom multiple samples were available displayed a similar pattern of expression in distant metastases and primary tumors. The median survival time was 14.3 months in patients without DCC expression and 21.4 months in patients with DCC-positive tumors (log-rank test, P = .04); the 2-year survival rates were 8.5% and 42.5%, respectively. Response rates to chemotherapy were not significantly different between the two groups. By multivariate analysis, DCC protein expression maintained its prognostic value and showed to be the single best predictor of survival, with a relative risk of 2.16.

Conclusion

Our results indicate that expression of the DCC protein in CRC metastases is similar to that observed in the corresponding primary tumors and represents a dominant predictor of survival in patients with unresectable, advanced CRC who are undergoing palliative FU-based chemotherapy.
Bone Mineral Density Among Premenopausal Women With Early Breast Cancer in a Randomized Trial of Adjuvant Endocrine Therapy
Authors: Sverrisdóttir Á. , Fornander T. , Jacobsson H. , von Schoultz E. , Rutqvist L.E.
Published: September 2004

Purpose

To examine the effects on bone mineral density of 2 years of treatment with a luteinizing hormone-releasing hormone (LHRH) agonist alone or in combination with tamoxifen or tamoxifen alone in premenopausal breast cancer.

Patients and Methods

We recruited 89 women from two centers in Stockholm participating in a randomized multicenter trial of three different endocrine approaches in the adjuvant setting (Zoladex in Premenopausal Patients Trial). The women were assigned to receive the LHRH agonist goserelin with or without tamoxifen, tamoxifen alone, or no endocrine therapy. The treatment was given for 2 years. We measured total-body bone density before start of treatment and at 12, 24, and 36 months.

Results

After 2 years of treatment, there was a significant loss of bone mineral density (mean change, −5%; P < .001) in the women receiving goserelin alone. The combined goserelin and tamoxifen treatment, as well as tamoxifen alone, resulted in a lesser but statistically significant decline in bone mineral density (mean change, −1.4%; P = .02; and −1.5%; P < .001). One year after cessation of treatment, the goserelin group alone showed a partial recovery from bone loss (mean change, 1.5%; P = .02).

Conclusion

Two years of ovarian ablation from goserelin treatment caused a significant reduction in bone mineral density but there was a partial recovery from the bone loss 1 year after cessation of treatment. The addition of tamoxifen seems to partially counteract the demineralizing effects of goserelin.
Phase II Trial of Bortezomib for Patients With Advanced Renal Cell Carcinoma
Authors: Kondagunta G. Varuni , Drucker Beverly , Schwartz Lawrence , Bacik Jennifer , Marion Stephanie , Russo Paul , Mazumdar Madhu , Motzer Robert J.
Published: September 2004

Purpose

To assess the efficacy and toxicity of bortezomib (Velcade; Milennium Pharmaceuticals Inc, Cambridge, MA; formerly PS-341) in patients with metastatic renal cell carcinoma (RCC).

Patients and Methods

Thirty-seven patients with metastatic RCC were treated with bortezomib. The first 25 patients enrolled onto the trial were treated with a dose of 1.5 mg/m2. The dose was decreased to 1.3 mg/m2 for the subsequent 12 patients, because more than 50% of the patients treated at the higher dose required dose reductions. Bortezomib was given by intravenous administration on a twice-weekly schedule for 2 weeks followed by 1 week without treatment until progression or unacceptable toxicity occurred. Twenty-three patients (62%) previously had undergone nephrectomy, and 19 patients (51%) had previously been treated with cytokine therapy.

Results

Of the 37 assessable patients, the best response was a partial response in four patients (11%; 95% CI, 3% to 25%) and stable disease in 14 patients (38%; 95% CI, 23% to 55%). The four patients with partial response experienced response durations of 8, 8+, 15+, and 20+ months. Grade 2 or 3 sensory neuropathy was present in 10 patients (53%) overall. One patient in the 1.5 mg/m2 group had grade 3 sensory neuropathy; no grade 3 sensory neuropathy was seen in the 1.3 mg/m2 group.

Conclusion

The results of this trial suggest that bortezomib has an antitumor effect in individual patients with metastatic RCC. The small proportion of patients who achieved a partial response does not support routine use in metastatic RCC. Efforts to identify the molecular profile associated with clinical response or combination therapy with interferon alfa or other novel agents, may be considered.
Irinotecan Plus Gemcitabine Results in No Survival Advantage Compared With Gemcitabine Monotherapy in Patients With Locally Advanced or Metastatic Pancreatic Cancer Despite Increased Tumor Response Rate
Authors: Rocha Lima Caio M. , Green Mark R. , Rotche Robert , Miller Wilson H. , Jeffrey G. Mark , Cisar Laura A. , Morganti Adele , Orlando Nicoletta , Gruia Gabriela , Miller Langdon L.
Published: September 2004

Purpose

This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer.

Patients and Methods

IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety.

Results

In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% CI, 4.7 to 7.5 months) and 6.6 months for GEM (95% CI, 5.2 to 7.8 months; log-rank P = .789). Tumor response rates were 16.1% (95% CI, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% CI, 1.9% to 8.6%) for GEM (χ2 P < .001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P = .352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar.

Conclusion

IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival.
TheArabidopsis thalianaSNF2 homolog AtBRM controls shoot development and flowering
Authors: Farrona Sara , Hurtado Lidia , Bowman John L. , Reyes José C.
Published: September 2004

Chromatin remodeling is essential for the reprogramming of transcription associated with development and cell differentiation. The SWI/SNF complex was the first chromatin remodeling complex characterized in yeast and Drosophila. In this work we have characterized an Arabidopsis thaliana homolog of Brahma, the ATPase of the Drosophila SWI/SNF complex. As its Drosophila counterpart, Arabidopsis thalianaBRAHMA (AtBRM) is a nuclear protein present in a high molecular mass complex. Furthermore, the N terminus of AtBRM interacts, in the two-hybrid system, with CHB4 (AtSWI3C), an Arabidopsis homolog of the yeast SWI/SNF complex subunit SWI3. The AtBRM gene is primarily expressed in meristems,organ primordia and tissues with active cell division. Silencing of the expression of the AtBRM gene by RNA interference demonstrated that AtBRM is required for vegetative and reproductive development. The AtBRM silenced plants exhibited a reduction in overall plant size with small and curled leafs, as well as a reduction in the size of the inflorescence meristem. In the absence of AtBRM, Arabidopsis flowers have small petals and stamens, immature anthers, homeotic transformations and reduced fertility. The AtBRM silenced plants flower earlier than wild-type plants both under inductive and non-inductive photoperiods. Furthermore, levels of CO, FT and SOC1 transcripts were up-regulated under non-inductive conditions suggesting that AtBRM is a repressor of the photoperiod-dependent flowering pathway.
An in vivo comparative study of sonic, desert and Indian hedgehog reveals that hedgehog pathway activity regulates epidermal stem cell homeostasis
Authors: Adolphe Christelle , Narang Monica , Ellis Tammy , Wicking Carol , Kaur Pritinder , Wainwright Brandon
Published: September 2004

Despite the well-characterised role of sonic hedgehog (Shh) in promoting interfollicular basal cell proliferation and hair follicle downgrowth, the role of hedgehog signalling during epidermal stem cell fate remains largely uncharacterised. In order to determine whether the three vertebrate hedgehog molecules play a role in regulating epidermal renewal we overexpressed sonic(Shh), desert (Dhh) and Indian (Ihh) hedgehog in the basal cells of mouse skin under the control of the human keratin 14 promoter. We observed no overt epidermal morphogenesis phenotype in response to Ihh overexpression, however Dhh overexpression resulted in a range of embryonic and adult skin manifestations indistinguishable from Shh overexpression. Two distinct novel phenotypes were observed amongst Shh and Dhh transgenics, one exhibiting epidermal progenitor cell hyperplasia with the other displaying a complete loss of epidermal tissue renewal indicating deregulation of stem cell activity. These data suggest that correct temporal regulation of hedgehog activity is a key factor in ensuring epidermal stem cell maintenance. In addition, we observed Shh and Dhh transgenic skin from both phenotypes developed lesions reminiscent of human basal cell carcinoma (BCC), indicating that BCCs can be generated despite the loss of much of the proliferative (basal) compartment. These data suggest the intriguing possibility that BCC can arise outside the stem cell population. Thus the elucidation of Shh (and Dhh)target gene activation in the skin will likely identify those genes responsible for increasing the proliferative potential of epidermal basal cells and the mechanisms involved in regulating epidermal stem cell fate.
Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages
Authors: Mustonen Tuija , Ilmonen Maritta , Pummila Marja , Kangas Aapo T. , Laurikkala Johanna , Jaatinen Risto , Pispa Johanna , Gaide Olivier , Schneider Pascal , Thesleff Irma , Mikkola Marja L.
Published: September 2004

Organs developing as appendages of the ectoderm are initiated from epithelial thickenings called placodes. Their formation is regulated by interactions between the ectoderm and underlying mesenchyme, and several signalling molecules have been implicated as activators or inhibitors of placode formation. Ectodysplasin (Eda) is a unique signalling molecule in the tumour necrosis factor family that, together with its receptor Edar, is necessary for normal development of ectodermal organs both in humans and mice. We have shown previously that overexpression of the Eda-A1 isoform in transgenic mice stimulates the formation of several ectodermal organs. In the present study, we have analysed the formation and morphology of placodes using in vivo and in vitro models in which both the timing and amount of Eda-A1 applied could be varied. The hair and tooth placodes of K14-Eda-A1transgenic embryos were enlarged, and extra placodes developed from the dental lamina and mammary line. Exposure of embryonic skin to Eda-A1 recombinant protein in vitro stimulated the growth and fusion of placodes. However, it did not accelerate the initiation of the first wave of hair follicles giving rise to the guard hairs. Hence, the function of Eda-A1 appears to be downstream of the primary inductive signal required for placode initiation during skin patterning. Analysis of BrdU incorporation indicated that the formation of the epithelial thickening in early placodes does not involve increased cell proliferation and also that the positive effect of Eda-A1 on placode expansion is not a result of increased cell proliferation. Taken together, our results suggest that Eda-A1 signalling promotes placodal cell fate during early development of ectodermal organs.
β-actin is required for mitochondria clustering and ROS generation in TNF-induced, caspase-independent cell death
Authors: Li Jinquan , Li Qinxi , Xie Changchuan , Zhou Huamin , Wang Yuqian , Zhang Na , Shao Hanjuan , Chan Siu Chiu , Peng Xuanxian , Lin Sheng-Cai , Han Jiahuai
Published: September 2004

Tumor necrosis factor (TNF)-α induces caspase-independent cell death in the fibrosarcoma cell line L929. This cell death has a necrotic phenotype and is dependent on production of reactive oxygen species (ROS) in the mitochondria. To identify genes involved in this TNF-induced, ROS-dependent cell death pathway, we utilized retrovirus insertion-mediated random mutagenesis to generate TNF-resistant L929 cell lines and we subsequently identified genes whose mutations are responsible for the TNF-resistant phenotype. In one such resistant line, β-actin was disrupted by viral insertion, and subsequent reconstitution of β-actin expression levels in the mutant line Actinmut restored its sensitivity to TNF. Resistance to TNF in Actinmut cells is signal specific since the sensitivity to other death stimuli is either unchanged or even increased. Comparable NF-κB activation and p38 phosphorylation in TNF-treated wild-type and Actinmut cells also indicates that reduced expression of actin only selectively blocked some of the TNF-induced cellular changes. Actin cleavage involved in apoptosis does not occur in TNF-treated L929 cell death, as in HeLa cells. Consistent over-expression of a caspase-cleaved product, a 15 kDa actin fragment, had no effect on TNF-induced necrosis of L929 cell. By contrast, TNF-induced mitochondria clustering and ROS production were dramatically reduced in Actinmut cells, indicating that actin-deficiency-mediated TNF resistance is most likely due to impaired mitochondrial responses to TNF stimulation. Our findings suggest that a full complement of actin is required for transduction of a cell death signal to mitochondria in TNF-treated L929 cells.
Stresses in rotating cross-ply laminated hollow cylinders with arbitrary thickness
Authors: Chen W Q , Lee Kang Yong
Published: September 2004

The stress analysis of a rotating finite cross-ply laminated composite hollow cylinder with two ends simply supported is conducted with the Coriolis acceleration effect involved. The state-space approach is employed together with the layerwise method as well as the Fourier expansion technique. The analysis is completely based on the exact elasticity equations so that hollow cylinders with arbitrary thickness can be readily dealt with. Numerical comparison with exact solution of a rotating infinite hollow cylinder without the Coriolis effect shows good agreement.
Finite element bending behaviour of composite hyperbolic paraboloidal shells with various edge conditions
Authors: Sahoo S , Chakravorty D
Published: September 2004

A general finite element procedure with an eight-noded isoparametric curved quadratic element is presented to investigate the static behaviour of laminated composite hyperbolic paraboloidal shells bounded by straight edges (commonly called hypar shells). Numerical results are obtained for uniformly loaded laminated composite hypar shells with six practical boundary conditions, where the edges are differently restrained. Eight different types of lamination including single layered and multi-layered, cross-ply and angle-ply, symmetric and antisymmetric stacking orders are chosen. The numerical results of different shell actions of 48 combinations are furnished to estimate their relative performances. The authors further propose typical comparative performance matrix to study the relative efficiencies of different stacking combinations, which will be a great help in design.
Failure model for composite materials under quasi-static crushing conditions
Authors: Morthorst M , Horst P
Published: September 2004

This paper presents a failure model to simulate the crushing mechanisms of fabric composite materials. In order to realize delamination processes and resulting lamina bending modes a multi-layered discretization is applied which is composed of shell and solid elements representing the laminate plies and the resin phase. The differentiation between the two phases enables the implementation of both in-plane failure and delamination fracture criteria and appropriate parametric degradation functions. To verify the fracture and degradation model, quasi-static tests with various compression directions have been carried out. The tests were performed using truncated conical shells of different specimen geometries fabricated with glass/epoxy prepreg. Among a qualitative comparison of the experimental and simulated failure behaviour the numerical model parameters are mainly obtained by curve fitting based on the measured load characteristics. The numerical simulations compare well with the experimental results, proving the applicability of the model for fabric composites under various loading conditions.
On static and fatigue strength determination of carbon fibre/epoxy composites Part 1: Experiments
Authors: Xiong J. J , Shenoi R. A , Wang S. P , Wang W. B
Published: September 2004

This work seeks to investigate the static and fatigue properties and the failure mechanisms of T300/QY8911 carbon-fibre-reinforced composite laminates with different layups to optimize the stacking sequence effect. Three different layups have been studied, namely, [45/02/-45/902/-45/0/45/90]s, [45/-45/0/-45/0/45/90/45/0/-45]s and [45/0/-45/0/-45/0/45/0/90/0]s. The results for static strength and fatigue residual strength under different fatigue stress amplitudes are evaluated and compared with each other. The damage and failure mechanisms of the composite laminates are discussed. It is observed that all tension-tension fatigue damage patterns of the notched laminates are similar while the tension-tension fatigue properties vary with the laminate layup. The reduction of stress concentration caused by the tension-tension fatigue damage leads to an improvement of the residual strength of the notched specimens in contrast to their static strength properties. The damage mechanics of the notched laminates under compression-compression loading are more complex than those of the tension-tension fatigue specimens; their damage patterns are influenced by the test clamping fixture, the layup, the size of specimens and the diameter of the hole. The residual strengths are lower than those of the specimens without fatigue damage. It is verified that in a high-temperature and moisture environment, there is a decrease in static compression strength. The results of this study provide an insight into fatigue damage development in composites and constitute a fundamental basis for the development of a strain-based residual strength model.
Approximate prediction methods for notch stresses and strains under elastic-plastic and creep conditions
Authors: Hyde T H , Sabesan R , Leen S. B
Published: September 2004

This paper describes general techniques for predicting notch stresses and strains under elastic-plastic and creep conditions. A linear interpolation method, usually used in creep analysis, is adapted for use in predicting elastic-plastic stresses and strains and the Neuber and the Molski-Glinka methods, usually used in elastic-plastic analyses, are adapted to predict peak creep stresses at notches in components. The accuracy of the methods is assessed by comparing predictions based on them with results obtained from elastic-plastic and creep finite element analyses.
Elastic strains around cracked cold-expanded fastener holes measured using the synchrotron X-ray diffraction technique
Authors: Stefanescu D , Steuwer A , Owen R A , Nadri B , Edwards L , Fitzpatrick M. E , Withers P. J
Published: September 2004

In this work, the capability of the synchrotron X-ray diffraction technique to measure changes in the residual strains caused by fatigue crack growth from cold-expanded holes in an aluminium alloy plate has been investigated. The measurement technique was validated by comparing the synchrotron measurements around uncracked holes with those obtained on similar specimens using the neutron diffraction and Sachs' techniques. Measurements were performed with and without superimposed tensile mechanical loading and the results compared with analytical results. The improved spatial resolution of the synchrotron technique relative to the other methods has allowed the strain fields around a fatigue crack growing from a cold-expanded hole to be evaluated in the unloaded state and at two loading levels. Only at the higher load does the crack appear to open along its full length.
Strains in steel bars of reinforced concrete elements subjected to repeated loads
Authors: Fantilli A P , Vallini P
Published: September 2004

To evaluate the strains in a steel bar of a reinforced concrete structure under repeated loads, a mechanical model is proposed. More precisely, a reinforcing bar embedded in a concrete cylinder subjected to uniaxial actions is modelled. In the proposed one-dimensional approach, both the nonlinear fracture mechanics of concrete and the bond-slip between the two materials are taken into account, since they affect the structural response of several reinforced concrete structures in the serviceability conditions and in the ultimate limit state. When cyclic actions are applied and previous cracks close up again, the interaction between the fictitious crack model of concrete in tension and the bond-slip near the crack is investigated. During the unloading phase of each cycle, only through refinement of the damage effects, with regard to the classical bond and cohesive models, can the hysteretic behaviour of the reinforced concrete structures be modelled. The strains in the bar, computed with the proposed model, seem to be in good agreement with those measured in the tests made by Bresler and Bertero.
Re-etched grids for large-strain measurement in fine-blanking
Authors: Leung Y. C , Chan L. C , Tang C. Y , Lee T. C
Published: September 2004

This paper presents an experimental remeshing process for the large strain analysis of fine-blanking. The research is to be carried out mainly because the severe and localized deformation of fine-blanking greatly obstructs the measurement of strains. In order to solve this problem, a new experimental remeshing process was developed to measure the strain in the major deformation areas of fine-blanking. Without this newly developed process, a more intensive and practical strain analysis of fine-blanking could not have been achieved. Therefore, a study of this remeshing process, with a step increment of 20 per cent, until the total punch penetration is 80 per cent of the material's thickness, is to be performed to verify its effectiveness. Low-carbon steel sheets of JISG3101 were used to split blanks. As a consequence, findings showed that an increase in the total punch penetration will clearly induce an exponential increase in the effective strain, and the severity of deformation will be augmented with the increase in the total punch penetration.
Stress concentration at crossholes in thick cylindrical vessels
Authors: Makulsawatudom P , Mackenzie D , Hamilton R
Published: September 2004

Elastic stress concentration factors (SCFs) for internally pressurized thick cylindrical vessels with radial and offset circular and elliptical crossholes are presented. Three forms of intersection between the crosshole and main bore are considered: plain, chamfered and blend radiused. The minimum SCF was found to occur for the plain intersection configuration, with the peak stress at the crotch corner between the main bore and crosshole on the longitudinal plane of symmetry. Incorporating a chamfer or blend radius at the intersection reduces the stress concentration at the main bore but introduces higher peak stress elsewhere in the chamfer or blend region.
On static and fatigue strength determination of carbon fibre/epoxy composites Part 2: Theoretical formulation
Authors: Xiong J. J , Shenoi R. A , Wang S. P , Wang W. B
Published: September 2004

This paper outlines a practical model to evaluate fatigue residual strength for reliability-based design. A new formulation is presented for a fatigue-driven residual strength surface based on controlling fatigue strain. The parameter determination formulae of the residual strength surface are established to deal with the test data effectively and easily. Finally, the model is applied to experimental data, demonstrating the practical and effective use of the proposed model. It is shown that fatigue-driven residual strength can be obtained realistically according to the small sample test data using the new formulae.
An integrated approach for measuring near-surface and subsurface residual stress in engineering components
Authors: Stefanescu D , Truman C. E , Smith D. J
Published: September 2004

This paper presents measurements performed using an integrated centre hole drilling-deep hole drilling technique on two components: a butt-welded plate and a rail. The results were compared with those available from other measurement techniques and with finite element (FE) simulations of the residual stresses. It was found that incremental centre hole drilling and deep hole drilling worked well as complementary techniques. Subsurface deep hole drilling measurements performed in the welded plate at two locations produced very similar results and evidence of good repeatability. The present experimental results were found to be in reasonable agreement with other measurements and FE predictions of residual stresses.