Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma

PURPOSE: The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS: Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses. RESULTS: Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks. CONCLUSION: At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.     

A comparative study of interval and conventional training in thoroughbred racehorses

Eight horses with previous racing experience were used in a comparative study of training methods for Thoroughbred racehorses. They were randomly assigned to two groups of four horses each. One group was trained using an interval training method (IT) and the other using conventional training (CT) methods. Peak heart rates, heart rate recovery curves, peak plasma lactate levels, plasma lactate clearance rates and run times were used to evaluate differences in the training methods. Peak heart rates, heart rate recovery curves, and run times were not significantly different between the groups. However, higher lactate production and increased plasma lactate clearance by the IT group demonstrated an increased anaerobic capacity.     

Parameterization of the MISO IFC rate region: the case of partial channel state information

We study the achievable rate region of the multipleinput single-output (MISO) interference channel (IFC), under the assumption that all receivers treat the interference as additive Gaussian noise. We assume the case of two users, and that the channel state information (CSI) is only partially known at the transmitters. Our main result is a characterization of Paretooptimal transmit strategies, for channel matrices that satisfy a certain technical condition. Numerical examples are provided to illustrate the theoretical results.     

Effect of acid deposition on quantity and quality of dissolved organic matter in soil-water

The aim of this study was to explore how acid deposition may affect the concentration and quality of dissolved organic matter (DOM) in soil-water. This was done by a small-scale acidification experiment during two years where 0.5 × 0.5 m(2) plots were artificially irrigated with water with different sulfuric acid content, and soil-water was sampled using zero-tension lysimeters under the O-horizon. The DOM was characterized using absorbance, fluorescence, and size exclusion chromatography analyses. Our results showed lower mobility of DOM in the high acid treatment. At the same time, there was a significant change in the DOM quality. Soil-water in the high acid treatment exhibited DOM that was less colored, less hydrophobic, less aromatic, and of lower molecular weight, compared to the low acid treatment. This supports the hypothesis that reduction in sulfur deposition is an important driver behind the ongoing brownification of surface waters in many regions.     

Film-forming capability in rough surface EHL investigated using contact resistance

Highly loaded machine elements such as gears and cams have a non-smooth surface topography that is created during manufacturing. It is well known that the film-building properties of such surfaces may be different from those that are perfectly smooth. The capability to form a separating film may also be altered in time due to run-in phenomena. In this study, a smooth steel ball was loaded against rough steel discs and run under pure rolling as well as sliding conditions. Several different steel surfaces were tested under nominal EHL conditions, where the contact was monitored by means of its electrical resistance and capacitance. Each surface was first run in for 15 min, followed by a sweep-in speed determining the lift-off curve. Electrical contact measurements were continuously conducted during run in as well as lift-off. Fully formulated gear oil and its base fluid were used as test lubricants. Results show that run in of a surface seems to be a competition between conformation of surface topography and tribofilm formation. At the tested conditions, the formation of a tribofilm is dependent on the initial surface topography and is created rapidly causing less metal–metal contact. This film also seems to effectively prohibit changes in surface topography causing less structural run in than expected.     

Methods of measuring susceptibility of anaerobic bacteria to trovafloxacin, including quality control parameters

Three methods approved by the National Committee for Clinical Laboratory Standards for testing the susceptibility of anaerobic bacteria were used to evaluate the fluoroquinolone, trovafloxacin. The methods gave essentially comparable results with 126 anaerobes and with three quality control strains. A collaborative study defined the quality control range for trovafloxacin MICs. Trovafloxacin had good in vitro activity against the more common anaerobes (MIC 90 < = or 2.0 micrograms/ml).     

Location and co-location in retail: a probabilistic approach using geo-coded data for metropolitan retail markets

In this paper, we employ geo-coded data at a fine spatial resolution for Sweden’s metropolitan areas to assess retail co-location. Retail clusters and their place in urban space are assessed from several angles. The probability of a specific type of retail unit to be established in a 250 by 250 m square is modelled as a function of (i) the presence of other similar retail establishments, (ii) the presence of stores that belong to other retail sectors and (iii) other characteristics of the square area, and its access to demand in the pertinent urban landscape. The analysis clarifies which types of retail clusters one can expect to find in a metropolitan region, as well as their relationship to the urban landscape. We analyse three distinct types of stores: clothing, household appliances, and specialized stores. Stores with high intensities of interaction are co-located, and predominantly located close to the urban cores, consistent with predictions from bid rent theory and central place theory. We further document negative location tendencies between shops that sell frequently purchased products and shops that sell durables. Moreover, our results highlight the importance of demand in the close surroundings, which is particularly strong for small-scale establishments.     

Space-time finite elements for a simplified thermo-metallurgical problem relevant to casting

The non-linear thermo-metallurgical problem, relevant for the cooling of a molten metal including the macro-segregation that occurs during the cooling process, is studied here. Due to the strong non-linearities involved in phase transformations, it is necessary to use a fine resolution in space-time in a finite element approximation in order to meet accuracy requirements. We derive space-time FE-methods based on the discontinuous and continuous Galerkin method in time for the energy equation. This formulation integrates the stored energy exactly for a given heat flux. When macro-segregation is incorporated into the model, the problem can be formulated in such a way that the phase-transition drives a flow of species. In addition, diffusion is possible throughout the domain. The model can be further rewritten using a potential approach. By this approach for modelling macro-segregation, we are able to obtain discretizations that guarantee that the balance equations are satisfied, and it is possible to solve the phase-transition problem either as a field problem or as a local problem (defined by a local evolution rule).