Search

Background LAF237 is potent DPP-4 inhibitor and under development as an oral anti-diabetic agent. It is expected to stimulate glucose-dependent insulin secretion. Deconvolution of C-peptide (C-Pep) levels is used to estimate insulin secretion rates (ISR).1 The objective of the present work was to assess the effect of LAF237 on C-pep clearance (CL) in patients with type 2 diabetes (T2D). Methods In a randomized placebo-controlled study, 20 patients with T2D received either LAF237 (100 mg bid, n=9) or placebo (PBO n=11) for 28 days. Blood samples were collected for measuring C-pep, insulin, glucose and other variables. The present work focuses on C-pep levels and DPP-4 activity. The endogenous C-pep levels were measured for 24 hr before and after in both groups. DPP-4 activity was measured 2 hr after each dose. Results DPP-4 activity was inhibited 98 and 97% 2 hr after morning and evening doses. C-pep levels vs. time over 24 hr on day-1 (predose) and day1 were superimposible. AUCs for C-pep were 48.3±18.1 and 47.0±15.6 nM.hr for the LAF237 group on days -1 and 1, respectively (p=0.783). When comparing the C-pep AUCs in patients treated with LAF237 to PBO on day 1, no difference was observed either (p=0.54). Conclusions DPP-4 activity was completely inhibited by LAF237. C-pep levels remained unchanged after a single day treatment with LAF237. LAF237 did not alter C-pep CL, supporting the use of C-pep levels to estimate ISR during LAF237 treatment. Clinical Pharmacology & Therapeutics (2005) 77, P56–P56; doi: 10.1016/j.clpt.2004.12.105

Formant frequencies of sung vowels are modified at higher pitches because of formant tuning, leading to a reduction in intelligibility as the formants converge with increasing F0. Formant frequencies are also dependent on language‐specific pronunciation requirements. The question of whether language‐specific characteristics of sung vowels are maintained through pitch‐effected formant tuning has not previously been examined. Sustained vowels from five similar positions on the vowel quadrilateral in four languages, English, Dutch, French, and Hungarian, were sung in a similar singing style over a range of pitches by a professional female singer who was proficient in singing each of these languages. Formant frequencies were extracted and the magnitudes of the voice partials computed from the average spectrum. The results showed an increase in F1 for the high vowels of all languages, but in the mid–low vowels there were some language differences in the direction of vowel shift as F0 increased. In addition, th...

The visible world provides a rich and wondrous tapestry for observation and speculation. Where it cannot be directly experienced, it can be pictured in varying degrees of fidelity or abstractness. On the simplest of intuitive grounds, illustrations should thus serve as valuable teaching tools, bringing to the eye what otherwise can only be imagined. Evidence of a widespread acceptance of this truism is found in the pervasiveness of illustrations in school textbooks; the producers and consumers of instructional textbooks clearly believe that illustrations have an important role to play in education.

The study is concerned with a longitudinal acoustic analysis of two sets of recordings from the same four speakers over an interval of between 29 and 50 years. The aim was to determine whether there is any evidence for age-related acoustic changes. Our analysis showed that the same speakers have lower f0, a lower F1, a marginally lower F2, and an unchanging or sometimes higher F3 in their later recordings. There is some suggestion from these data that the change in F1-f0 in Bark from earlier to late recordings is proportional to the change in F3-F2 in Bark. This suggests that there is shift in the speaker space roughly along a diagonal in the phonetic height x backness plane with increasing age.

Aim: The purpose of this study was to explore helpful processes in therapy, focusing on the specific client and therapist activities that can lead to helpful effects. Method: Ten clients took part ...