Numerical modelling of skin tumour tissue with temperature-dependent properties for dynamic thermography.

Dynamic thermography has been clinically proven to be a valuable diagnostic technique for skin tumour detection as well as for other medical applications, and shows many advantages over static thermography. Numerical modelling of heat transfer phenomena in biological tissue during dynamic thermography can aid the technique by improving process parameters or by estimating unknown tissue parameters based on measurement data. This paper presents a new non-linear numerical model of multilayer skin tissue containing a skin tumour together with thermoregulation response of the tissue during the cooling-rewarming process of dynamic thermography. The thermoregulation response is modelled by temperature-dependent blood perfusion rate and metabolic heat generation. The aim is to describe bioheat transfer more realistically. The model is based on the Pennes bioheat equation and solved numerically using a subdomain BEM approach treating the problem as axisymmetrical. The paper includes computational tests for Clark II and Clark IV tumours, comparing the models using constant and temperature-dependent properties which showed noticeable differences and highlighted the importance of using a local thermoregulation model. Results also show the advantage of using dynamic thermography for skin tumour screening and detection at an early stage. One of the contributions of this paper is a complete sensitivity analysis of 56 model parameters based on the gradient of the surface temperature difference between tumour and healthy skin. The analysis shows that size of the tumour, blood perfusion rate, thermoregulation coefficient of the tumour, body core temperature and density and specific heat of the skin layers in which the tumour is embedded are important for modelling the problem, and so have to be determined more accurately to reflect realistic skin response of the investigated tissue, while metabolic heat generation and its thermoregulation are not.

Censoring weighted separate-and-conquer rule induction from survival data.

OBJECTIVES: Rule induction is one of the major methods of machine learning. Rule-based models can be easily read and interpreted by humans, that makes them particularly useful in survival studies as they can help clinicians to better understand analysed data and make informed decisions about patient treatment. Although of such usefulness, there is still a little research on rule learning in survival analysis. In this paper we take a step towards rule-based analysis of survival data. METHODS: We investigate so-called covering or separate-and-conquer method of rule induction in combination with a weighting scheme for handling censored observations. We also focus on rule quality measures being one of the key elements differentiating particular implementations of separate-and-conquer rule induction algorithms. We examine 15 rule quality measures guiding rule induction process and reflecting a wide range of different rule learning heuristics. RESULTS: The algorithm is extensively tested on a collection of 20 real survival datasets and compared with the state-of-the-art survival trees and random survival forests algorithms. Most of the rule quality measures outperform Kaplan-Meier estimate and perform at least equally well as tree-based algorithms. CONCLUSIONS: Separate-and-conquer rule induction in combination with weighting scheme is an effective technique for building rule-based models of survival data which, according to predictive accuracy, are competitive with tree-based representations.

Excitatory action of vasopressin in the brain of the rat: role of cAMP signaling.

Brain vasopressin plays a role in behavioral and cognitive functions and in pathological conditions. Relevant examples are pair bonding, social recognition, fear responses, stress disorders, anxiety and depression. At the neuronal level, vasopressin exerts its effects by binding to V1a receptors. In the brainstem, vasopressin can excite facial motoneurons by generating a sustained inward current which is sodium-dependent, tetrodotoxin-insensitive and voltage-gated. This effect is independent of intracellular calcium mobilization and is unaffected by phospholipase Cß (PLCß) or protein kinase C (PKC) inhibitors. There are two major unsolved problems. (i) What is the intracellular signaling pathway activated by vasopressin? (ii) What is the exact nature of the vasopressin-sensitive cation channels? We performed recordings in brainstem slices. Facial motoneurons were voltage-clamped in the whole-cell configuration. We show that a major fraction, if not the totality, of the peptide effect was mediated by cAMP signaling and that the vasopressin-sensitive cation channels were directly gated by cAMP. These channels appear to exclude lithium, are suppressed by 2-aminoethoxydiphenylborane (2-APB) and flufenamic acid (FFA) but not by ruthenium red or amiloride. They are distinct from transient receptor channels and from cyclic nucleotide-regulated channels involved in visual and olfactory transduction. They present striking similarities with cation channels present in a variety of molluscan neurons. To our knowledge, the presence in mammalian neurons of channels having these properties has not been previously reported. Our data should contribute to a better knowledge of the neural mechanism of the central actions of vasopressin, and may be potentially significant in view of clinical applications.

Oxytocin and vasopressin enhance synaptic transmission in the hypoglossal motor nucleus of young rats by acting on distinct receptor types.

Hypoglossal (XII) motoneurons innervate extrinsic and intrinsic muscles of the tongue and control behaviors such as suckling, swallowing, breathing or chewing. In young rats, XII motoneurons express V1a vasopressin and oxytocin receptors. Previous studies have shown that activation of these receptors induces direct powerful excitation in XII motoneurons. In addition, by activating V1a receptors vasopressin can also enhance inhibitory synaptic transmission in the XII nucleus. In the present work, we have further characterized the effect of these neuropeptides on synaptic transmission in the XII nucleus. We have used brainstem slices of young rats and whole-cell patch clamp recordings. Oxytocin enhanced the frequency of spontaneous inhibitory postsynaptic currents by a factor of two and a half. GABAergic and glycinergic events were both affected. The oxytocin effect was mediated by uterine-type oxytocin receptors. Vasopressin and oxytocin also increased the frequency of excitatory synaptic currents, the enhancement being sixfold for the former and twofold for the latter compound. These effects were mediated by V1a and oxytocin receptors, respectively. Miniature synaptic events were unaffected by either vasopressin or oxytocin. This indicates that the peptide-dependent facilitation of synaptic currents was mediated by receptors located on the somatodendritic membrane of interneurons or premotor neurons, and not by receptors sited on axon terminals contacting XII motoneurons. Accordingly, recordings obtained from non-motoneurons located near the border of the XII nucleus showed that part of these cells possess functional V1a and oxytocin receptors whose activation leads to excitation. Some of these neurons could be antidromically activated following electrical stimulation of the XII nucleus, suggesting that they may act as premotor neurons. We propose that in young rats, oxytocin and vasopressin may function as neuromodulators in brainstem motor circuits responsible of tongue movements.

Action of tachykinins in the hippocampus: facilitation of inhibitory drive to GABAergic interneurons.

By acting on neurokinin 1 (NK1) receptors, neuropeptides of the tachykinin family can powerfully excite rat hippocampal GABAergic interneurons located in the CA1 region and by this way indirectly inhibit CA1 pyramidal neurons. In addition to contact pyramidal neurons, however, GABAergic hippocampal interneurons can also innervate other interneurons. We thus asked whether activation of tachykinin-sensitive interneurons could indirectly inhibit other interneurons. The study was performed in hippocampal slices of young adult rats. Synaptic events were recorded using the whole-cell patch clamp technique. We found that substance P enhanced GABAergic inhibitory postsynaptic currents in a majority of the interneurons tested. Miniature, action potential-independent inhibitory postsynaptic currents were unaffected by substance P, as were evoked inhibitory synaptic currents. This suggests that the peptide acted at the somatodendritic membrane of interneurons, rather than at their axon terminals. The effect of substance P was mimicked by a selective NK1 receptor agonist, but not by neurokinin 2 (NK2) or neurokinin 3 (NK3) receptor agonists, and was suppressed by a NK1 selective receptor antagonist. In contrast to substance P, oxytocin, another peptide capable of activating hippocampal interneurons, had no effect on the inhibitory synaptic drive onto interneurons. We conclude that tachykinins, by acting on NK1 receptors, can influence the hippocampal activity by indirectly inhibiting both pyramidal neurons and GABAergic interneurons. Depending on the precise balance between these effects, tachykinins may either activate or depress hippocampal network activity.

Abnormal inspiratory depth in Phox2a haploinsufficient mice.

Mutations of genes encoding Phox2a or Phox2b transcription factors induce modifications of different brainstem neuronal networks. Such modifications are associated with defects in breathing behavior at birth. In particular, an abnormal breathing frequency is observed in Phox2a-/- mutant mice, resulting from abnormal development of the locus coeruleus (LC) nucleus. However, the role of Phox2a proteins in the establishment of respiratory neuronal pathways is unknown, largely because mutants die shortly after birth. In the present study, we examined the effects of a haploinsufficiency of the Phox2a gene. Phox2a heterozygotes survive and exhibit a significantly larger inspiratory volume both during normoxic breathing and in response to hypoxia and a delayed maturation of inspiratory duration compared to wild-type animals. This phenotype accompanied by an unaltered frequency is evident at birth and persists until at least postnatal day 10. Morphological analyses of Phox2a+/- animals revealed no anomaly in the LC region, but highlighted an increase in the number of cells expressing tyrosine hydroxylase enzyme, a marker of chemoafferent neurons, in the petrosal sensory ganglion. These data indicate that Phox2a plays a critical role in the ontogeny of the reflex control of inspiration.

Ontogeny of central rhythm generation in chicks and rodents.

Recent studies help in understanding how the basic organization of brainstem neuronal circuits along the anterior-posterior (AP) axis is set by the Hox-dependent segmentation of the neural tube in vertebrate embryos. Neonatal respiratory abnormalities in Krox20(-/-), Hoxa1(-/-) and kreisler mutant mice indicate the vital role of a para-facial (Krox20-dependent, rhombomere 4-derived) respiratory group, that is distinct from the more caudal rhythm generator called Pre-Bötzinger complex. Embryological studies in the chick suggest homology and conservation of this Krox20-dependent induction of parafacial rhythms in birds and mammals. Calcium imaging in embryo indicate that rhythm generators may derive from different cell lineages within rhombomeres. In mice, the Pre-Bötzinger complex is found to be distinct from oscillators producing the earliest neuronal activity, a primordial low-frequency rhythm. In contrast, in chicks, maturation of the parafacial generator is tightly linked to the evolution of this primordial rhythm. It seems therefore that ontogeny of brainstem rhythm generation involves conserved processes specifying distinct AP domains in the neural tube, followed by diverse, lineage-specific regulations allowing the emergence of organized rhythm generators at a given AP level.

Application of Lagrangian particle transport model to tuberculosis (TB) bacteria UV dosing in a ventilated isolation room.

The aim of this work is to define the basis for design guidelines that will minimise the risk of exposure from airborne organisms in hospital isolation rooms. This research employs an algorithm that combines an understanding of the interaction between the room airflow and the ultra violet (UV) system. The airflow in such a room is complex and therefore cannot easily be accounted for by existing design guidance. The main findings were firstly, the mean lifetime of the ventilated particles does not reduce in proportion with increasing ventilation rate. Secondly, an increase in the ventilation rate reduces the effectiveness of ultra violet germicidal irradiation (UVGI) with only a limited increase in the number of particles that are ventilated. Finally, there is a social benefit attached to this project from the point of view of helping people who are vulnerable as well as reducing their risk of being exposed to possible tuberculosis infection. The significance of these findings is to provide the engineer and the architect with an essential tool to ensure good design practice. It is also important to ensure that the methodology can be applicable to most isolation room uses.

Natural environment and thermal behaviour of Dimetrodon limbatus.

This paper examines the body temperature variation of Dimetrodon during the different seasons of the year. The effect of the sail of Dimetrodon on its body temperature is also evaluated. It is shown that the sail of pelycosaurs provided an advantage to the reptile by warming it up quicker in the morning in cold environments. This would be a benefit, allowing Dimetrodon to prey on large reptiles, above 55kg, in the early morning while they were sluggish. From the results presented a climate similar to that of March for Cyprus could be representative of that of Permian period.

The Shrugged-Off Shoulder: A Comparison of Patients With Recurrent Shoulder Subluxations and Dislocations.

In brief: Patients with recurrent anterior shoulder subluxations and dislocations are compared in terms of recurrences, delays in diagnoses, and treatments. Based on these criteria, the subluxers experienced substantially more disability than the dislocators. Since shoulder instability is such a frequent problem in athletes (sports caused the initial episode in nearly 70% of the patients), professionals who deal with athletic injuries must be aware of the shoulder subluxation syndrome, recognize It early, and quickly initiate appropriate treatments.