Pulsed arterial spin labeling perfusion imaging at 3 T: estimating the number of subjects required in common designs of clinical trials

Pulsed arterial spin labeling (PASL) is an increasingly common technique for noninvasively measuring cerebral blood flow (CBF) and has previously been shown to have good repeatability. It is likely to find a place in clinical trials and in particular the investigation of pharmaceutical agents active in the central nervous system. We aimed to estimate the sample sizes necessary to detect regional changes in CBF in common types of clinical trial design including (a) between groups, (b) a two-period crossover and (3) within-session single dosing. Whole brain CBF data were acquired at 3 T in two independent groups of healthy volunteers at rest; one of the groups underwent a repeat scan. Using these data, we were able to estimate between-groups, between-session and within-session variability along with regional mean estimates of CBF. We assessed the number of PASL tag-control image pairs that was needed to provide stable regional estimates of CBF and variability of regional CBF across groups. Forty tag-control image pairs, which take approximately 3 min to acquire using a single inversion label delay time, were adequate for providing stable CBF estimates at the group level. Power calculations based on the variance estimates of regional CBF measurements suggest that comparatively small cohorts are adequate. For example, detecting a 15% change in CBF, depending on the region of interest, requires from 7-15 subjects per group in a crossover design, 6-10 subjects in a within-session design and 20-41 subjects in a between-groups design. Such sample sizes make feasible the use of such CBF measurements in clinical trials of drugs.     

Perturbation-free measurement of the harmonics-to-noise ratio in voice signals using pitch synchronous harmonic analysis.

The measurement of the harmonics-to-noise ratio (HNR) in speech signals gives an indication of the aperiodicity of the speech waveform. This may be due to the presence of jitter, shimmer, additive noise, waveshape change, or some unknown combination of these factors. In order to estimate the HNR as a measure of the additive noise component only, the contaminating effects of the other contributory components must first be removed. A pitch synchronous harmonic analysis is proposed to overcome this problem. The procedure takes advantage of the time scale compression-frequency expansion property of the Fourier series in order to eliminate jitter and shimmer. Successive spectra are added by harmonic number as opposed to frequency location, and perturbation is removed due to the fact that the relative heights of the harmonic components remain the same for scaled signals. The technique is examined on synthetically generated voice signals. A discussion of the results is given in terms of human voice signals, characterization of jitter, vocal tract filtering effects, perturbation mechanisms, nonlinear dynamics, and the possibility of developing the method for use with inverse filtering strategies.     

Oligonucleotide-directed assembly of materials: defined oligomers.

A nano-architectural system that has high variability while maintaining component specificity is described. Tetraphenylcyclobutadiene(cyclopentadienyl)cobalt complexes and phenyleneethynylene trimers were synthesized and subsequently modified with oligonucleotides utilizing standard phosphoramidite chemistry. The resulting oligonucleotide modified organics (OMOs) were characterized by UV-vis spectroscopy, fluorescence spectroscopy, and phosphate analysis. Hybridization of these OMOs resulted in a series of self-assembled oligomeric hybrids of varying length and topology. These hybrids were characterized by melting temperature, polyacrylamide gel electrophoresis, and fluorescence spectroscopy. This model system demonstrates the power of DNA to self-assemble modules of interest-independent of the module itself.     

A synthesis of crambescidin 359

A potentially biomimetic synthesis of the guanidine-containing marine natural product crambescidin 359 via a double Michael addition of guanidine to a suitably functionalised bis-enone is reported.     

Type I Toeplitz algebras

The class of Toeplitz algebras associated to ordered groups is important in the analysis of Toeplitz operators on the generalised Hardy spaces defined by such groups. The conditions under which these Toeplitz algebras are Type I C^*-algebras are investigated.