Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2), a beta integrin antagonist, in patients with solid tumours

To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five –amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1–16 mg kg−1), receiving ATN-161 administered as a 10-min infusion thrice weekly. Pharmacokinetic sampling of blood and urine over 7 h was performed on Day 1. Twenty-six patients received from 1 to 14 4-week cycles of treatment. The total number of cycles administered to all patients was 86, without dose-limiting toxicities. At dose levels above 0.5 mg kg−1, mean total clearance and volume of distribution showed dose-independent pharmacokinetics (PKs). At 8.0 and 16.0 mg kg−1, clearance of ATN-161 was reduced, suggesting saturable PKs. Dose escalation was halted at 16 mg kg−1 when drug exposure (area under the curve) exceeded that associated with efficacy in animal models. There were no objective responses. Six patients received more than four cycles of treatment (>112 days). Three patients received 10 or more cycles (⩾280 days). ATN-161 was well tolerated at all dose levels. Approximately, 1/3 of the patients in the study manifested prolonged stable disease. These findings suggest that ATN-161 should be investigated further as an antiangiogenic and antimetastatic cancer agent alone or with chemotherapy

Filled pauses in Hungarian: Their phonetic form and function

Filled pauses are natural occurrences in spontaneous speech and they may turn up at any level of the speech planning process and in a number of functions. The aim of this paper is to find out whether the diverse functions of filled pauses correlate with diverse articulations resulting in diverse acoustic structures. Spontaneous narratives are used as research material. The duration of the filled pauses and the frequency values of their first two formants are analyzed. The most frequent form, schwa, shows function-dependent realizations as confirmed by the durational values and by the second formant values of these vowel-like sounds

Analysing Change: Complex Rather than Dialectical?

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.This article offers a discussion of dialectics from a complexity perspective. Dialectics is a term much utilized but infrequently defined. This article suggests that a spectrum of ideas exist concerning understandings of dialectics. We are particularly critical of Hegelian dialectics, which we see as anthropocentric and teleological. While Marxist approaches to dialectics, in the form of historical materialism, marked a break from the idealist elements of Hegelian dialectics, they retained traces of this approach. The article offers a partial discussion of essential elements of dialectics, which we consider to be the analysis of change, the centrality of contradiction, and the methodology of abstraction. Points of overlap with complexity thinking are highlighted, together with those points where complexity thinking and dialectical approaches diverge. We conclude with some suggestions as to how complexity thinking might contribute to a development of dialectical approaches