A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

Fostering Creativity in New Product Development through Entrepreneurial Decision Making

Research has emphasized the importance of employees' individual entrepreneurial decision making for innovation. In this context, practised creativity as the ability to perceive and exploit creative opportunities, can be regarded as a crucial requirement for employees in new product development. We discuss the application of decision making logic as an important antecedent of practised creativity in new product development. We survey 219 employees from new product development departments of German product and service firms. Results indicate that the use of entrepreneurial decision making logic positively impacts practised creativity; comparably we find indicators that the use of causal decision making logic negatively influences creativity. The effects significantly depend on the moderating role of uncertainty. The results contribute to the literature of creativity, entrepreneurship and new product development by theoretically and empirically revealing effectuation as antecedent to practised creativity. The results open promising avenues for future research and allow the derivation of valuable guidelines for practitioners. Aligning the new product development process to support employees' entrepreneurial decision making may help generating practised creativity.     

On-line cylinder fault diagnostics for internal combustion engines

The ability to continuously monitor internal combustion engines for the existence and location of faults can improve engine reliability and reduce operating costs. The diagnostics method is based on recording the engine speed fluctuations at the flywheel and at the front end of the engine over one combustion cycle. From the speed fluctuations, the cylinder-to-cylinder variations of the net engine torque are computed. The performance deterioration of an individual cylinder is detected as a drop of computed torque. The diagnostic hardware consists of a digital engine speed data acquisition system and an embedded controller and is suited for in-vehicle installation. The method, suited for any multicylinder engine, detects the location and severity of faults during normal engine operation. Adjustments for individual engines of the same class are not required     

Differentiation of Crude Lipopolysaccharides from Escherichia coli Strains Using Fourier Transform Infrared Spectroscopy and Chemometrics

Crude phenol‐phase extracts containing bacterial lipopolysaccharides (LPS) from 5 strains of Escherichia coli were investigated to differentiate the strains using Fourier transform infrared (FTIR) spectroscopy and multivariate statistical analysis. The strains used were E. coli K12, E. coli DH5α, E. coli O157:H7, E. coli O157:H12, and E. coli O157:H19. LPS‐containing extracts were isolated from each E. coli strain using a hot phenol‐water extraction procedure. The extracts were 1st analyzed by deoxycholic acid‐polyacrylamide gel electrophoresis and visualized by silver‐staining. Analysis of the extracts from E. coli K12 and E. coli DH5α showed rough‐type LPS on the lower half of the gel, whereas E. coli O157:H7, E. coli O157:H12, and E. coli O157:H19 yielded abundant smooth LPS (high‐molecular‐weight LPS that include the O‐polysaccharides). Spectra (4000 cm^‐1 to 700 cm^‐1) of crude E. coli LPS extracts and intact cells were collected using a FTIR spectrometer. Spectral data were compressed by principle component analysis and analyzed using canonical variate analysis (CVA) of 4000 cm^‐1 to 700 cm^‐1 or 1200 cm^‐1 to 900 cm^‐1 spectral regions. CVA showed better separation between strains using LPS extracts than intact cells in the 1200 cm^‐1 to 900 cm^‐1 spectral region. The same separation trend was found using Mahalanobis distances that quantified spectral differences between the E. coli strains, providing 80% and >95% correct classifications of intact cells and LPS extracts, respectively. This article is the first to report the successful differentiation of E. coli strains at a serotype level using FTIR spectra of bacterial phenol‐phase extracts (crude LPS preparations).     

Improved Thermal Cycling Durability of Thermal Barrier Coatings Manufactured by PS-PVD

The plasma spray-physical vapor deposition (PS-PVD) process is a promising method to manufacture thermal barrier coatings (TBCs). It fills the gap between traditional thermal spray processes and electron beam physical vapor deposition (EB-PVD). The durability of PS-PVD manufactured columnar TBCs is strongly influenced by the compatibility of the metallic bondcoat (BC) and the ceramic TBC. Earlier investigations have shown that a smooth BC surface is beneficial for the durability during thermal cycling. Further improvements of the bonding between BC and TBC could be achieved by optimizing the formation of the thermally grown oxide (TGO) layer. In the present study, the parameters of pre-heating and deposition of the first coating layer were investigated in order to adjust the growth of the TGO. Finally, the durability of the PS-PVD coatings was improved while the main advantage of PS-PVD, i.e., much higher deposition rate in comparison to EB-PVD, could be maintained. For such coatings, improved thermal cycling lifetimes more than two times higher than conventionally sprayed TBCs, were measured in burner rigs at ~1250 °C/1050 °C surface/substrate exposure temperatures.     

Recurrence of haemolytic-uraemic syndrome in renal transplants: a single-centre report

BACKGROUND: The incidence of recurrence of haemolytic-uraemic syndrome (HUS) in renal allografts appears to vary by centre, with the highest rates reported from the University of Minnesota. It is possible that the high rate of HUS recurrence at this institution reflects a transplant population skewed towards patients with a form of HUS that is more likely to recur in the allograft. METHODS: This study examined whether the initial episode of HUS in the native kidneys was preceded by a diarrhoeal prodrome ('classical HUS') or not ('atypical HUS'), and evaluated transplant outcomes in 24 patients who received 36 transplants at the University of Minnesota between 31 May 1972 and 31 December 1994. RESULTS: Eighteen of the 24 patients had atypical HUS, three had classical HUS, and in three patients the presence or absence of a diarrhoeal prodrome could not be determined. Recurrent HUS, defined as microangiopathic haemolytic anaemia, thrombocytopenia, renal insufficiency, and allograft biopsy findings compatible with HUS, occurred 16 times in 14 grafts in 11 patients. Nine of these patients had atypical HUS, one had classical HUS, and in one the nature of the prodrome could not be determined. Eleven of the 14 initial recurrences took place within 2 months of transplant. Recurrence was not more frequent in patients who received cyclosporin or antilymphocyte preparations. Actuarial analysis using matched controls showed poorer graft survival in patients with a primary diagnosis of HUS (P = 0.007), due to the high frequency of graft loss in HUS patients with recurrence. CONCLUSION: Based upon these data and a review of the literature, it can be concluded that the risk of recurrence of HUS in the allograft is confined almost entirely to patients with atypical forms of HUS.     

Identification of the cellular location of internalized Escherichia coli O157:H7 in mung bean, Vigna radiata, by immunocytochemical techniques

Escherichia coli O157:H7 has been associated with numerous outbreaks involving fresh produce. Previous studies have shown that bacteria can be internalized within plant tissue and that this can be a source of protection from antimicrobial chemicals and environmental conditions. However, the types of tissue and cellular locations the bacteria occupy in the plant following internalization have not been addressed. In this study, immunocytochemical techniques were used to localize internalized E. coli O157:H7 expressing green fluorescent protein in germinated mung bean (Vigna radiata) hypocotyl tissue following contamination of intact seeds. An average of 13 bacteria per mm(3) were localized within the sampled tissue. The bacteria were found to be associated with every major tissue and corresponding cell type (cortex, phloem, xylem, epidermis, and pith). The cortical cells located on the outside of the vascular bundles contained the majority of the internalized bacteria (61%). In addition, the bacteria were localized primarily to the spaces between the cells (apoplast) and not within the cells. Growth experiments were also performed and demonstrated that mung bean plants could support the replication of bacteria to high levels (10(7) CFU per plant) following seed contamination and that these levels could be sustained over a 12-day period. Therefore, E. coli O157:H7 can be internalized in many different plant tissue types after a brief seed contamination event, and the bacteria are able to grow and persist within the plant.     

Recurrence of steroid-resistant nephrotic syndrome in kidney transplants is associated with increased acute renal failure and acute rejection

We performed 73 kidney transplants in 51 patients with steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerular sclerosis (FSG) ages 18.4 +/- 12.8 (mean +/- SD) years. Recurrence of SRNS, defined by rapid onset of proteinuria, hypoalbuminemia and/or > 95% epithelial cell foot process effacement with or without the presence of FSG, occurred in 26 grafts in 16 patients. Acute renal failure (ARF) occurred in 16 of 26 (61.5%) grafts with recurrence versus 7 of 47 (14.9%) grafts without recurrence (P < 0.0001). ARF occurred in 4 of 9 (44.4%) living-related donor (LRD) recipients with recurrence and 3 of 21 (12.5%) LRD recipients without recurrence (NS). ARF in cadaver donor (CAD) recipients with recurrence was 12 of 17 (70.5%) versus 4 of 23 (17.4%) without recurrence (P < 0.0001). ARF was also higher in LRD or CAD with recurrence than in a control group of non-SRNS patients matched for age, sex and time of transplantation. Graft survival at one year was lower in patients with recurrence and ARF [4 of 16 (25%)] compared to patients with recurrence and no ARF [9 of 11 (82%), P < 0.01]. There was no difference in graft survival in patients without recurrence who did or did not have ARF. One or more acute rejection episodes occurred in all 16 patients with ARF and recurrence, in all 7 patients with ARF without recurrence, and in 7 of 10 patients with recurrence without ARF compared with only 11 of 40 (28%) of patients with neither recurrence nor ARF (P < 0.0001, < 0.001 and < 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

European survey on post-consumer poly(ethylene terephthalate) (PET) materials to determine contamination levels and maximum consumer exposure from food packages made from recycled PET.

Typical contamination and the frequency of misuse of poly(ethylene terephthalate) (PET) bottles are crucial parameters in the risk assessment of post-consumer recycled (PCR) PET intended for bottle-to-bottle recycling for direct food contact applications. Owing to the fact that misuse of PET bottles is a rare event, sustainable knowledge about the average concentration of hazardous compounds in PCR PET is accessible only by the screening of large numbers of samples. In order to establish average levels of contaminants in PET source materials for recycling, PET flakes from commercial washing plants (689 samples), reprocessed pellets (38) and super-clean pellets (217) were collected from 12 European countries between 1997 and 2001. Analysis of these materials by headspace gas chromatography revealed average and maximum levels in PCR PET of 18.6 and 86.0 mg kg-1 for acetaldehyde and 2.9 and 20 mg kg-1 for limonene, respectively. Acetaldehyde and limonene are typical compounds derived from PET itself and from prior PET bottle contents (flavouring components), respectively. Maximum levels in PCR PET of real contaminants such as misuse chemicals like solvents ranged from 1.4 to 2.7 mg kg-1, and statistically were shown to result from 0.03 to 0.04% of recollected PET bottles that had been misused. Based on a principal component analysis of the experimental data, the impact of the recollecting system and the European Union Member State where the post-consumer PET bottles had been collected on the nature and extent of adventitious contaminants was not significant. Under consideration of the cleaning efficiency of super-clean processes as well as migration from the bottle wall into food, it can be concluded that the consumer will be exposed at maximum to levels < 50 ng total misuse chemicals day-1. Therefore, PCR PET materials and articles produced by modern superclean technologies can be considered to be safe in direct food applications in the same way as virgin food-grade PET.     

A fuzzy logic controller for an ABS braking system

Anti-blocking system (ABS) brake controllers pose unique challenges to the designer: a) For optimal performance, the controller must operate at an unstable equilibrium point, b) Depending on road conditions, the maximum braking torque may vary over a wide range, c) The tire slippage measurement signal, crucial for controller performance, is both highly uncertain and noisy, d) On rough roads, the tire slip ratio varies widely and rapidly due to tire bouncing, and e) The braking system contains transportation delays which limit the control system bandwidth. A digital controller design was chosen which combines a fuzzy logic element and a decision logic network. The controller identifies the current road condition and generates a command braking pressure signal, based on current and past readings of the slip ratio and brake pressure. The controller detects wheel blockage immediately and avoids excessive slipping. The ABS system performance is examined on a quarter vehicle model with nonlinear elastic suspension. The parallelity of the fuzzy logic evaluation process ensures rapid computation of the controller output signal, requiring less time and fewer computation steps than controllers with adaptive identification. The robustness of the braking system is investigated on rough roads and in the presence of large measurement noise. This paper describes design criteria, and the decision and rule structure of the control system. The simulation results present the system's performance on various road types and under rapidly changing road conditions