Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Mapping the relative contribution of gray matter activity vs. volume in brain PET: a new approach.

Interpretation of brain positron emission tomography (PET) in terms of function vs. structure is ambiguous owing to the partial volume effect (PVE). Therefore, observed differences in tracer distribution could reflect differences in either activity or volume, a problem that applies principally to gray matter (GM) since white matter (WM) virtually always has uniform activity. To assess the contribution of GM volume vs. activity, we implemented a method to directly compare PET images with underlying structure, and applied it to resting-state (18)Fluoro-deoxy-glucose-PET (FDG) of healthy subjects. Methods. Average GM and WM PVE-corrected mean FDG uptake values were applied onto co-registered segmented magnetic resonance imaging data sets to generate a "virtual PET" in which activity is proportional to GM volume and resolution set to that of PET. The raw PET and virtual PET values were then compared across the sample of subjects, first voxel-wise to detect clusters with significant activity-volume mismatch, and second within regions-of-interest (ROI) to quantify mismatches between unsmoothed voxel values. Results. Relative to volume, there was significant hyperactivity of most GM structures of the dorsal brain-except the thalamus-and significant hypoactivity of the temporal lobe, hippocampal region, and cerebellum, consistent across the voxel- and ROI-based analyses. Conclusion. As applied to normals, our method documented the expected contribution of functional activity independently of local differences in GM volume in the normal pattern of FDG uptake, and disclosed marked heterogeneities in functional activity per unit GM volume among structures. This generic method should find applications in pathological states as well as for other PET and SPECT radiotracers.

Pressure wave propagation in fluid-filled co-axial elastic tubes. Part 1: Basic theory.

Our work is motivated by ideas about the pathogenesis of syringomyelia. This is a serious disease characterized by the appearance of longitudinal cavities within the spinal cord. Its causes are unknown, but pressure propagation is probably implicated. We have developed an inviscid theory for the propagation of pressure waves in co-axial, fluid-filled, elastic tubes. This is intended as a simple model of the intraspinal cerebrospinal-fluid system. Our approach is based on the classic theory for the propagation of longitudinal waves in single, fluid-filled, elastic tubes. We show that for small-amplitude waves the governing equations reduce to the classic wave equation. The wave speed is found to be a strong function of the ratio of the tubes' cross-sectional areas. It is found that the leading edge of a transmural pressure pulse tends to generate compressive waves with converging wave fronts. Consequently, the leading edge of the pressure pulse steepens to form a shock-like elastic jump. A weakly nonlinear theory is developed for such an elastic jump.

Pressure wave propagation in fluid-filled co-axial elastic tubes. Part 2: Mechanisms for the pathogenesis of syringomyelia.

Our aim in this paper is to use a simple theoretical model of the intraspinal cerebrospinal-fluid system to investigate mechanisms proposed for the pathogenesis of syringomyelia. The model is based on an inviscid theory for the propagation of pressure waves in co-axial, fluid-filled, elastic tubes. According to this model, the leading edge of a pressure pulse tends to steepen and form an elastic jump, as it propagates up the intraspinal cerebrospinal-fluid system. We show that when an elastic jump is incident on a stenosis of the spinal subarachnoid space, it reflects to form a transient, localized region of high pressure within the spinal cord that for a cough-induced pulse is estimated to be 50 to 70 mm Hg or more above the normal level in the spinal subarachnoid space. We propose this as a new mechanism whereby pressure pulses created by coughing or sneezing can generate syrinxes. We also use the same analysis to investigate Williams' suck mechanism. Our results do not support his concept, nor, in cases where the stenosis is severe, the differential-pressure-propagation mechanism recently proposed by Greitz et al. Our analysis does provide some support for the piston mechanism recently proposed by Oldfield et al. and Heiss et al. For instance, it shows clearly how the spinal cord is compressed by the formation of elastic jumps over part of the cardiac cycle. What appears to be absent for this piston mechanism is any means whereby the elastic jumps can be focused (e.g., by reflecting from a stenosis) to form a transient, localized region of high pressure within the spinal cord. Thus it would seem to offer a mechanism for syrinx progression, but not for its formation.