Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer.

PURPOSE: Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. PATIENTS AND METHODS: Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. RESULTS: Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. CONCLUSION: Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.

Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma

Purpose: Some phase II studies have suggested that the combination of interferons (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM) increases the antitumor activity of DTIC alone. In an attempt to confirm this hypothesis, a randomized study was performed with the further intent of observing whether low doses of recombinant interferon alfa-2a (rIFNα2a) could be as effective as intermediate doses. Patients and Methods: Two hundred sixty-six patients were randomized onto three different treatment arms: DTIC 800 mg/m 2 intravenously (IV) days 1 and 21; DTIC plus rIFNα2a 9 mIU intramuscularly (IM) daily; and DTIC plus rIFNα2a 3 mIU IM three times per week. Major prognostic factors were well balanced among the three arms. Chemotherapy was administered for a maximum of eight cycles. After 6 months of therapy, rIFNα2a was continued until disease progression at 3 mIU three times per week in responding patients who had received the combined treatment. Results: The percentage of objective responses did not differ among the three groups (20%, 28%, and 23%, respectively), although a significant prolongation of response duration was observed when rIFNα2a was added to DTIC (2.6 v 8.4 v 5.5 months, respectively). However, this improvement in response duration did not translate into an amelioration of overall survival. The addition of rIFNα2a led to the onset of flu-like syndrome, but in no case was it necessary to withdraw the treatment program and no toxic deaths or life-threatening toxicities were reported. Conclusion: In this study, rIFNα2a significantly prolonged response duration, whereas no effects on response rate and survival were observed; rIFNα2a 3 mIU appeared to be equally effective and better tolerated than 9 mIU.

Determination of ammonia based on the electro-oxidation of hydroquinone in dimethylformamide or in the room temperature ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide

The results detail a novel methodology for the electrochemical determination of ammonia based on its interaction with hydroquinone in DMF. It has been shown that ammonia reversibly removes protons from the hydroquinone molecules, thus facilitating the oxidative process with the emergence of a new wave at less positive potentials. The analytical utility of the proposed methodology has been examined with a linear range from 10 to 95 ppm and corresponding limit-of-detection of 4.2 ppm achievable. Finally, the response of hydroquinone in the presence of ammonia has been examined in the room temperature ionic liquid 1-ethyl-3-methylimidazolium bis(trifluormethylsulfonyl)imide, [EMIM][N(Tf)(2)]. Analogous voltammetric waveshapes to that observed in DMF were obtained, thereby confirming the viability of the method in either DMF or [EMIM][N(Tf)(2)] as solvent. (C) 2003 Elsevier B.V. All rights reserved.

Age-related changes in energy efficiency of gait, activity, and participation in children with cerebral palsy

Aim
The aim of this study was to use a prospective longitudinal study to describe age-related trends in energy efficiency during gait, activity, and participation in ambulatory children with cerebral palsy (CP).

Method
Gross Motor Function Measure (GMFM), Paediatric Evaluation of Disability Inventory (PEDI), and Lifestyle Assessment Questionnaire-Cerebral Palsy (LAQ-CP) scores, and energy efficiency (oxygen cost) during gait were assessed in representative sample of 184 children (112 male; 72 female; mean age 10y 9mo; range 4–16y) with CP. Ninety-four children had unilateral spastic CP, 84 bilateral spastic CP, and six had other forms of CP. Fifty-seven were classified as Gross Motor Function Classification System (GMFCS) level I, 91 as level II, 22 as level III, and 14 as level IV). Assessments were carried out on two occasions (visit 1 and visit 2) separated by an interval of 2 years and 7 months. A total of 157 participants returned for reassessment.

Results
Significant improvements in mean raw scores for GMFM, PEDI, and LAQ-CP were recorded; however, mean raw oxygen cost deteriorated over time. Age-related trends revealed gait to be most inefficient at the age of 12 years, but GMFM scores continued to improve until the age of 13 years, and two PEDI subscales to age 14 years, before deteriorating (p<0.05). Baseline score was consistently the single greatest predictor of visit 2 score. Substantial agreement in GMFCS ratings over time was achieved (?lw=0.74–0.76).

Interpretation
These findings have implications in terms of optimal provision and delivery of services for young people with CP to maximize physical capabilities and maintain functional skills into adulthood.

A Reliability Assessment Approach for the Urban Energy System and Its Application in Energy Hub Planning

With the increasing utilization of combined heat and power plants (CHP), electrical, gas, and thermal systems are becoming tightly integrated in the urban energy system (UES). However, the three systems are usually planned and operated separately, ignoring their interactions and coordination. To address this issue, the coupling point of different systems in the UES is described by the energy hub model. With this model, an integrated load curtailment method is proposed for the UES. Then a Monte Carlo simulation based approach is developed to assess the reliability of coordinated energy supply systems. Based on this approach, a reliability-optimal energy hub planning method is proposed to accommodate higher renewable energy penetration. Numerical studies indicate that the proposed approach is able to quantify the UES reliability with different structures. Also, optimal energy hub planning scheme can be determined to ensure the reliability of the UES with high renewable penetration.

Specifying and analysing networks of processes in CSPt (or in search of associativity)

In proposing theories of how we should design and specify networks of processes it is necessary to show that the semantics of any language we use to write down the intended behaviours of a system has several qualities. First in that the meaning of what is written on the page reflects the intention of the designer; second that there are no unexpected behaviours that might arise in a specified system that are hidden from the unsuspecting specifier; and third that the intention for the design of the behaviour of a network of processes can be communicated clearly and intuitively to others. In order to achieve this we have developed a variant of CSP, called CSPt, designed to solve the problems of termination of parallel processes present in the original formulation of CSP. In CSPt we introduced three parallel operators, each with a different kind of termination semantics, which we call synchronous, asynchronous and race. These operators provide specifiers with an expressive and flexible tool kit to define the intended behaviour of a system in such a way that unexpected or unwanted behaviours are guaranteed not to take place. In this paper we extend out analysis of CSPt and introduce the notion of an alphabet diagram that illustrates the different categories of events that can arise in the parallel composition of processes. These alphabet diagrams are then used to analyse networks of three processes in parallel with the aim of identifying sufficient constraints to ensure associativity of their parallel composition. Having achieved this we then proceed to prove associativity laws for the three parallel operators of CSPt. Next, we illustrate how to design and construct a network of three processes that satisfy the associativity law, using the associativity theorem and alphabet diagrams. Finally, we outline how this could be achieved for more general networks of processes.

Estimating Effective Slowdown of Tasks in Energy-Aware Clouds

Consolidation consists in scheduling multiple virtual machines onto fewer servers in order to improve resource utilization and to reduce operational costs due to power consumption. However, virtualization technologies do not offer performance isolation, causing applications’ slowdown. In this work, we propose a performance enforcing mechanism, composed of a slowdown estimator, and a interference- and power-aware scheduling algorithm. The slowdown estimator determines, based on noisy slowdown data samples obtained from state-of-the-art slowdown meters, if tasks will complete within their deadlines, invoking the scheduling algorithm if needed. When invoked, the scheduling algorithm builds performance and power aware virtual clusters to successfully execute the tasks. We conduct simulations injecting synthetic jobs which characteristics follow the last version of the Google Cloud tracelogs. The results indicate that our strategy can be efficiently integrated with state-of-the-art slowdown meters to fulfil contracted SLAs in real-world environments, while reducing operational costs in about 12%.