Functional MR of the primary auditory cortex: an analysis of pure tone activation and tone discrimination.

PURPOSETo use functional MR imaging to measure the effect of frequency (pitch), intensity (loudness), and complexity of auditory stimuli on activation in the primary and secondary auditory cortexes.METHODSMultiplanar echo-planar images were acquired in healthy subjects with normal hearing to whom auditory stimuli were presented intermittently. Functional images were processed from the echo-planar images with conventional postprocessing methods. The stimuli included pure tones with a single frequency and intensity, pure tones with the frequency stepped between 1,000, 2,000, 3,000, or 4,000 Hz, and spoken text. The pixels activated by each task in the transverse temporal gyrus (TTG) and the auditory association areas were tabulated.RESULTSThe pure tone task activated the TTG. The 1,000-Hz tone activated significantly more pixels in the TTG than did the 4,000-Hz tone. The 4,000-Hz tone activated pixels primarily in the medial TTG, whereas the 1,000-Hz tone activated more pixels in the lateral TTG. Higher intensity tones activated significantly more pixels than did lower intensity tones at the same frequency. The stepped tones activated more pixels than the pure tones, but the difference was not significant. The text task produced significantly more activation than did the pure tones in the TTG and in the auditory association areas. The more complex tasks (stepped tones and listening to text) tended to activate more pixels in the left hemisphere than in the right, whereas the simpler tasks activated similar numbers of pixels in each hemisphere.CONCLUSIONAuditory stimuli activate the TTG and the association areas. Activation in the primary auditory cortex depends on frequency, intensity, and complexity of the auditory stimulus. Activation of the auditory association areas requires more complex auditory stimuli, such as the stepped tone task or text reading.     

Specification of the Dose to Organs at Risk in External Beam Radiotherapy

Reporting of the clinical relevant dose to organs at risk (OR) and other normal tissues is crucial in trials and protocols where the aim is to assess late complications and to increase the therapeutic ratio for external beam radiotherapy. The dose distribution in normal tissues and ORs are, however, most often heterogeneous, at least when more than two opposing beams are applied. To decide the most clinical relevant dose with respect to late occurring complications is therefore not a straight forward problem. In this work we discuss what parameters characterise the dose-volume-histogram (DVH) best by calculating normal tissue complication probabilities (NTCPs) by using the Lyman model and various sets of statistical parameters drawn out from the DVHs. These NTCPs are compared to NTCPs calculated from the full DVHs, when the sets of parameters are evaluated. Our calculations indicate that the NTCP based on the Lyman model is best correlated to the D_max value, for serially organised tissues such as the spinal cord. For organs, described largely as tissues organised in parallel, the D_median or D_mean of the DVH may be applied. Our calculations reveal that D_mean is the parameter of choice when D_meclian is quite small, but when the two parameters approach each other, D_mediarl will be a better choice, using a unity volume fraction. For ORs characterised by a mixed serial and parallel functional structure, as the heart, neither D_max, D_median, nor D_mi,_an may predict the actual NTCP.     

Regulation of fibroblast-induced collagen gel contraction by interleukin-1β

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.     

Evidence that the Receptor for Soluble CD14:LPS Complexes may not be the Putative Signal-Transducing Molecule Associated with Membrane-Bound CD14

Membrane-bound CD14 acts as a receptor for lipopolysaccharide (LPS) on monocytes/macrophages and neutrophils. Studies have suggested that the activation of monocytes/macrophages by the binding of LPS to membrane-bound CD14 may require the association of a signal-transducing molecule with membrane-bound CD14. The observation that non-CD14 expressing cells, such as endothelial cells, can nevertheless be activated by a complex of LPS and a soluble form of CD14 (sCD14) suggests that the receptor for this complex may be identical to the signal transducing molecule associated with membrane-bound CD14. The studies described show that two CD14-specific MoAb are able to block the LPS-induced activation of endothelial cells but do not affect the response of monocytes to LPS. This suggests that the interaction of the sCD14:LPS complex with endothelial cells is distinct from the interaction of membrane-bound CD14 with its putative signal-transducing molecule.     

Increase in Power through Multivariate Analyses

Power to detect genetic and environmental influences increases not only with sample size but also with the number of measurements through longitudinal and/or multivariate designs, if those measurements correlate with each other. Power simulations are presented for uni- through quadrivariate cases, with differing genetic and environmental parameters. Even though subject attrition is a problem for most longitudinal studies, the gain in power available may more than make up for this shortcoming in many situations. In terms of planning studies to examine genetic and environmental influences, power calculations should not only consider sample size but number of measurements on particular phenotypes and their intercorrelations.