Phase I study of high-dose epirubicin and vinorelbine in previously untreated non-small-cell lung cancer stage IIIB-IV.

The aim of the study was to determine the maximum tolerated dose (MTD) for the combination of high-dose epirubicin and vinorelbine in chemotherapy-naive patients with inoperable non-small-cell lung cancer (NSCLC). Twenty-one patients with stage IIIB and IV NSCLC were treated in a single-centre study with escalating doses of epirubicin and vinorelbine given on an outpatient basis. The first dose level comprised epirubicin 100 mg m-2 on day 1 and vinorelbine 20 mg m-2 (days 1 and 8) given intravenously every 3 weeks. Escalating doses for epirubicin and vinorelbine were respectively 120 (day 1) and 20 (days 1 and 8), 120 (day 1) and 25 (days 1 and 8) and 135 (day 1) and 25 (days 1 and 8) mg m-2. Inclusion criteria were age < or = 75 years, ECOG performance score < or = 2 and normal renal, hepatic and bone marrow functions. Dose-limiting toxicities were thrombocytopenia grade II and neutropenia grade III on day 8, febrile neutropenia, and neutropenia lasting > 7 days. No dose-limiting toxicity (DLT) was observed at the first dose level; at the 135/25 mg m-2 dose level three out of six patients had a DLT which was considered as unacceptable. The only non-haematological toxicity reaching grade III was nausea/vomiting. One patient showed cardiac toxicity. No neurotoxicity and no treatment-related deaths were seen. The maximum tolerated dose of epirubicin and vinorelbine is 135 mg m-2 (day 1) and 25 mg m-2 (days 1 and 8) respectively, causing mainly haematological toxicity. The recommended dose of epirubicin and vinorelbine for phase II studies is found to be 120 mg m-2 and 20 mg m-2 respectively

Similarities between digits’ movements in grasping, touching and pushing

In order to find out whether the movements of single digits are controlled in a special way when grasping, we compared the movements of the digits when grasping an object with their movements in comparable single-digit tasks: pushing or lightly tapping the same object at the same place. The movements of the digits in grasping were very similar to the movements in the single-digit tasks. To determine to what extent the hand transport and grip formation in grasping emerges from a synchronised motion of individual digits, we combined movements of finger and thumb in the single-digit tasks to obtain hypothetical transport and grip components. We found a larger peak grip aperture earlier in the movement for the single-digit tasks. The timing of peak grip aperture depended in the same way on its size for all tasks. Furthermore, the deviations from a straight line of the transport component differed considerably between subjects, but were remarkably similar across tasks. These results support the idea that grasping should be regarded as consisting of moving the digits, rather than transporting the hand and shaping the grip

Drifting snow measurements on the Greenland Ice Sheet and their application for model evaluation

This paper presents autonomous drifting snow observations performed on the Greenland Ice Sheet in the fall of 2012. High-frequency snow particle counter (SPC) observations at ~ 1 m above the surface provided drifting snow number fluxes and size distributions; these were combined with meteorological observations at six levels. We identify two types of drifting snow events: katabatic events are relatively cold and dry, with prevalent winds from the southeast, whereas synoptic events are short lived, warm and wet. Precipitating snow during synoptic events disturbs the drifting snow measurements. Output of the regional atmospheric climate model RACMO2, which includes the drifting snow routine PIEKTUK-B, agrees well with the observed near-surface climate at the site, as well as with the frequency and timing of drifting snow events. Direct comparisons with the SPC observations at 1 m reveal that the model overestimates the horizontal snow transport at this level, which can be related to an overestimation of saltation and the typical size of drifting snow particles

A new method for tracking of motor skill learning through practical application of Fitts’ law

This article is made available through the Brunel Open Access Publishing Fund.A novel upper limb motor skill measure, task productivity rate (TPR) was developed integrating speed and spatial error, delivered by a practical motor skill rehabilitation task (MSRT). This prototype task involved placement of 5 short pegs horizontally on a spatially configured rail array. The stability of TPR was tested on 18 healthy right-handed adults (10 women, 8 men, median age 29 years) in a prospective single-session quantitative within-subjects study design. Manipulations of movement rate 10% faster and slower relative to normative states did not significantly affect TPR, F(1.387, 25.009) = 2.465, p = .121. A significant linear association between completion time and error was highest during the normative state condition (Pearson's r = .455, p < .05). Findings provided evidence that improvements in TPR over time reflected motor learning with possible changes in coregulation behavior underlying practice under different conditions. These findings extend Fitts’ law theory to tracking of practical motor skill using a dexterity task, which could have potential clinical applications in rehabilitation

Partitioning of melt energy and meltwater fluxes in the ablation zone of the west Greenland ice sheet

We present four years (August 2003–August 2007) of surface mass balance data from the ablation zone of the west Greenland ice sheet along the 67&amp;deg; N latitude circle. Sonic height rangers and automatic weather stations continuously measured accumulation/ablation and near-surface climate at distances of 6, 38 and 88 km from the ice sheet margin at elevations of 490, 1020 and 1520 m a.s.l. Using a melt model and reasonable assumptions about snow density and percolation characteristics, these data are used to quantify the partitioning of energy and mass fluxes during melt episodes. The lowest site receives very little winter accumulation, and ice melting is nearly continuous in June, July and August. Due to the lack of snow accumulation, little refreezing occurs and virtually all melt energy is invested in runoff. Higher up the ice sheet, the ice sheet surface freezes up during the night, making summer melting intermittent. At the intermediate site, refreezing in snow consumes about 10% of the melt energy, increasing to 40% at the highest site. The sum of these effects is that total melt and runoff increase exponentially towards the ice sheet margin, each time doubling between the stations. At the two lower sites, we estimate that radiation penetration causes 20–30% of the ice melt to occur below the surface

Reliability of computerized image analysis for the evaluation of serial synovial biopsies in randomized controlled trials in rheumatoid arthritis

Analysis of biomarkers in synovial tissue is increasingly used in the evaluation of new targeted therapies for patients with rheumatoid arthritis (RA). This study determined the intrarater and inter-rater reliability of digital image analysis (DIA) of synovial biopsies from RA patients participating in clinical trials. Arthroscopic synovial biopsies were obtained before and after treatment from 19 RA patients participating in a randomized controlled trial with prednisolone. Immunohistochemistry was used to detect CD3(+ )T cells, CD38(+ )plasma cells and CD68(+ )macrophages. The mean change in positive cells per square millimetre for each marker was determined by different operators and at different times using DIA. Nonparametric tests were used to determine differences between observers and assessments, and to determine changes after treatment. The intraclass correlations (ICCs) were calculated to determine the intrarater and inter-rater reliability. Intrarater ICCs showed good reliability for measuring changes in T lymphocytes (R = 0.87), plasma cells (R = 0.62) and macrophages (R = 0.73). Analysis by Bland–Altman plots showed no systemic differences between measurements. The smallest detectable changes were calculated and their discriminatory power revealed good response in the prednisolone group compared with the placebo group. Similarly, inter-rater ICCs also revealed good reliability for measuring T lymphocytes (R = 0.68), plasma cells (R = 0.69) and macrophages (R = 0.72). All measurements identified the same cell types as changing significantly in the treated patients compared with the placebo group. The measurement of change in total positive cell numbers in synovial tissue can be determined reproducibly for various cell types by DIA in RA clinical trials