The sympathetic release test: a test used to assess thermoregulation and autonomic control of blood flow

When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the subject is gently heated by placing the feet and calves in a commercially available foot warming pouch or immersing the feet and calves in warm water and wrapping the subject in blankets. Skin blood flow is estimated from measurements of skin temperature in the fingers. Normally skin temperature of the fingers is 65-75 degrees F in cool conditions (environmental temperature: 59-68 degrees F) and rises to 85-95 degrees F during body heating. Deviations in this pattern may mean that there is abnormal sympathetic vasoconstrictor control of skin blood flow. Abnormal skin blood flow can substantially impair an individual's ability to thermoregulate and has important clinical implications. During whole body heating, the skin temperature from three different skin sites is monitored and oral temperature is monitored as an index of core temperature. Students determine the fingertip temperature at which the reflex release of sympathetic activity occurs and its maximal attainment, which reflects the vasodilating capacity of this cutaneous vascular bed. Students should interpret typical sample data for certain clinical conditions (Raynaud's disease, peripheral vascular disease, and postsympathectomy) and explain why there may be altered skin blood flow in these disorders.

Measurement of nasal patency in anesthetized and conscious dogs

Experiments were undertaken to characterize a noninvasive chronic, model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Compound 48/80 was administered intranasally to elicit nasal congestion in five beagle dogs either by syringe (0.5 ml) in thiopental sodium-anesthetized animals or as a mist (0.25 ml) in the same animals in the conscious state. Effects of mast cell degranulation on nasal cavity volume as well as on minimal cross-sectional area (A(min)) and intranasal distance to A(min) (D(min)) were studied. Compound 48/80 caused a dose-related decrease in nasal cavity volume and A(min) together with a variable increase in D(min). Maximal responses were seen at 90-120 min. Compound 48/80 was less effective in producing nasal congestion in conscious animals, which also had significantly larger basal nasal cavity volumes. These results demonstrate the utility of using acoustic rhinometry to measure parameters of nasal patency in dogs and suggest that this model may prove useful in studies of the actions of decongestant drugs.

Acoustic rhinometry in the dog:a novel large animal model for studies of nasal congestion

The aim of this project was to develop and pharmacologically characterize an experimental dog model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Solubilized compound 48/80 (0.3-3.0%) was administered intranasally to thiopental anesthetized beagle dogs to elicit nasal congestion via localized mast cell degranulation. Compound 48/80-induced effects on parameters of nasal patency were studied in vehicle-treated animals, as well as in the same animals pretreated 2 hours earlier with oral d-pseudoephedrine or chlorpheniramine. Local mast cell degranulation caused a close-related decrease in nasal cavity volume and minimal cross-sectional area (Amin) together with a highly variable increase in nasal secretions. Maximal responses were seen at 90-120 minutes after 48/80 administration. Oral administration of the adrenergic agonist, d-pseudoephedrine (3.0 mg/kg), significantly antagonized all of the nasal effects of compound 48/80 (3.0%). In contrast, oral administration of the histamine H1 receptor antagonist chlorpheniramine (10 mg/kg) appeared to reduce the increased nasal secretions but was without effect on the compound 48/ 80-induced nasal congestion (i.e., volume and Amin). These results show the effectiveness of using acoustic rhinometry in this anesthetized dog model. The observations that compound 48/80-induced nasal congestion was prevented by d-pseudoephedrine pretreatment, but not by chlorpheniramine, suggest that this noninvasive model system may provide an effective tool with which to study the actions of decongestant drugs in preclinical investigations.

Role of nitric oxide in maintenance of basal oral tissue blood flow in anesthetized cats

Experiments were undertaken to determine if nitric oxide (NO) plays a role in regulation of basal blood flow in the oral cavity of pentobarbital anesthetized cats and, if so, to quantify this effect using dose-response relationships. Blood flow was continuously measured from the surface of the tongue and mandibular gingiva (laser-Doppler flowmetry) and from the lingual artery (ultrasonic flowmetry). Cardiovascular parameters also were recorded. Administration of the nonselective inhibitor of nitric oxide synthase (NOS), L-NAME (0.08-20 mg/kg i.v.), produced a dose-related increase of blood pressure associated with decreases of blood flow at all three measurement sites. Maximal blood flow depression of 50-60% was seen 30-60 min after administration of 1.25 mg/kg of L-NAME. D-NAME (1.25 mg/kg i.v.) was inactive at all sites. Subsequent administration of L-arginine partially reversed effects of L-NAME in the lingual artery and tongue, but not in the gingival circulation. The neuronally selective NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg i.p.), was devoid of effect on any of the measured parameters. These results suggest that endothelial (but not neuronally derived) NO plays an important role in control of basal blood flow in oral tissues of the cat.

A potential vulnerability locus for schizophrenia on chromosome 6p24-22:evidence for genetic heterogeneity

In 265 Irish pedigrees, with linkage analysis we find evidence for a vulnerability locus for schizophrenia in region 6p24-22. The greatest lod score, assuming locus heterogeneity, is 3.51 (P = 0.0002) with D6S296. Another test, the C test, also supported linkage, the strongest results being obtained with D6S296 (P = 0.00001), D6S274 (P = 0.004) and D6S285 (P = 0.006). Non-parametric analysis yielded suggestive, but substantially weaker, findings. This locus appears to influence the vulnerability to schizophrenia in roughly 15 to 30% of our pedigrees. Evidence for linkage was maximal using an intermediate phenotypic definition and declined when this definition was narrowed or was broadened to include other psychiatric disorders.

Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice

Whilst data recognise both myeloid cell accumulation during choroidal neovascularisation (CNV) as well as complement activation, none of the data has presented a clear explanation for the angiogenic drive that promotes pathological angiogenesis. One possibility that is a pre-eminent drive is a specific and early conditioning and activation of the myeloid cell infiltrate. Using a laser-induced CNV murine model, we have identified that disruption of retinal pigment epithelium (RPE) and Bruch's membrane resulted in an early recruitment of macrophages derived from monocytes and microglia, prior to angiogenesis and contemporaneous with lesional complement activation. Early recruited CD11b(+) cells expressed a definitive gene signature of selective inflammatory mediators particularly a pronounced Arg-1 expression. Accumulating macrophages from retina and peripheral blood were activated at the site of injury, displaying enhanced VEGF expression, and notably prior to exaggerated VEGF expression from RPE, or earliest stages of angiogenesis. All of these initial events, including distinct VEGF (+) Arg-1(+) myeloid cells, subsided when CNV was established and at the time RPE-VEGF expression was maximal. Depletion of inflammatory CCR2-positive monocytes confirmed origin of infiltrating monocyte Arg-1 expression, as following depletion Arg-1 signal was lost and CNV suppressed. Furthermore, our in vitro data supported a myeloid cell uptake of damaged RPE or its derivatives as a mechanism generating VEGF (+) Arg-1(+) phenotype in vivo. Our results reveal a potential early driver initiating angiogenesis via myeloid-derived VEGF drive following uptake of damaged RPE and deliver an explanation of why CNV develops during any of the stages of macular degeneration and can be explored further for therapeutic gain.

Seasonal patterns of body temperature daily rhythms in group-living cape ground squirrels Xerus inauris

Organisms respond to cyclical environmental conditions by entraining their endogenous biological rhythms. Such physiological responses are expected to be substantial for species inhabiting arid environments which incur large variations in daily and seasonal ambient temperature (T). We measured core body temperature (T) daily rhythms of Cape ground squirrels Xerus inauris inhabiting an area of Kalahari grassland for six months from the Austral winter through to the summer. Squirrels inhabited two different areas: an exposed flood plain and a nearby wooded, shady area, and occurred in different social group sizes, defined by the number of individuals that shared a sleeping burrow. Of a suite of environmental variables measured, maximal daily T provided the greatest explanatory power for mean T whereas sunrise had greatest power for T acrophase. There were significant changes in mean T and T acrophase over time with mean T increasing and T acrophase becoming earlier as the season progressed. Squirrels also emerged from their burrows earlier and returned to them later over the measurement period. Greater increases in T, sometimes in excess of 5°C, were noted during the first hour post emergence, after which T remained relatively constant. This is consistent with observations that squirrels entered their burrows during the day to 'offload' heat. In addition, greater T amplitude values were noted in individuals inhabiting the flood plain compared with the woodland suggesting that squirrels dealt with increased environmental variability by attempting to reduce their T-T gradient. Finally, there were significant effects of age and group size on T with a lower and less variable T in younger individuals and those from larger group sizes. These data indicate that Cape ground squirrels have a labile T which is sensitive to a number of abiotic and biotic factors and which enables them to be active in a harsh and variable environment.

Serum erythropoietic activity in acute anemia--an animal model

Serum erythropoietic activity and reticulocyte response to anemia were investigated using a rabbit model. In hemolytic anemia, induced by injections of phenylhydrazine on Day 0 the hemoglobin reached a nadir (mean, 6.23 g/dl) on Day 4 when SEA was maximal (mean, 765 mU/ml). In animals venesected on Day 0 and Day 1 to produce anemia of equal severity, the SEA was maximal (mean 235 mU/ml) on Day 2. In both groups the reticulocyte response peaked on Day 7--at 34% for the hemolytic group and 21% for the venesected group. The 2,3-diphosphoglycerate, measured on Day 4, was significantly reduced in the PHZ-treated group. In the venesected group the 2,3-DPG increased between Day 0 and Day 4. There were no concurrent changes in acid-base balance. These results imply that the degree of anemia is only one of the factors which influence the level of circulating SEA.

Erythropoietic response to hypobaric hypoxia in rabbits

Animals subjected to hypoxia become hypocapnic and after some hours show an increase in circulating erythropoietin. The steps involved in the increased production of erythropoietin in response to hypoxia are not fully understood, although it has been postulated that changes in coincident variables such as acid-base balance may contribute to the mechanism of increased erythropoietin production. A rabbit model has been used to determine the physiological changes which occur in short-term hypobaric hypoxia. After 1 h, no changes were found in pCO2, pH, P50, base excess, standard bicarbonate or serum erythropoietic activity (SEA). After 3 h the pCO2, pH, base excess and standard bicarbonate had decreased while the P50 and SEA had increased. After 6 h, although the pCO2 was still significantly reduced, the pH, base excess and standard bicarbonate had returned to the initial levels and maximal SEA values. 20-fold greater than the pre-hypoxia values were found. Overall the data are consistent with the view that the magnitude of the erythropoietic response to hypoxia is modified by changes in acid-base balance.

Transmit Antenna Selection for Interference Management in Cognitive Relay Networks

We propose transmit antenna selection (TAS) in decode-and-forward (DF) relaying as an effective approach to reduce the interference in underlay spectrum sharing networks with multiple primary users (PUs) and multiple antennas at the secondary users (SUs). We compare two distinct protocols: 1) TAS with receiver maximal-ratio combining (TAS/MRC) and 2) TAS with receiver selection combining (TAS/SC). For each protocol, we derive new closed-form expressions for the exact and asymptotic outage probability with independent Nakagami-m fading in the primary and secondary networks. Our results are valid for two scenarios related to the maximum SU transmit power, i.e., P, and the peak PU interference temperature, i.e., Q. When P is proportional to Q, our results confirm that TAS/MRC and TAS/SC relaying achieve the same full diversity gain. As such, the signal-to-noise ratio (SNR) advantage of TAS/MRC relaying relative to TAS/SC relaying is characterized as a simple ratio of their respective SNR gains. When P is independent of Q, we find that an outage floor is obtained in the large P regime where the SU transmit power is constrained by a fixed value of Q. This outage floor is accurately characterized by our exact and asymptotic results.

Advantages and limitations of navigation-based multicriteria optimization (MCO) for localized prostate cancer IMRT planning

Efficacy of inverse planning is becoming increasingly important for advanced radiotherapy techniques. This study's aims were to validate multicriteria optimization (MCO) in RayStation (v2.4, RaySearch Laboratories, Sweden) against standard intensity-modulated radiation therapy (IMRT) optimization in Oncentra (v4.1, Nucletron BV, the Netherlands) and characterize dose differences due to conversion of navigated MCO plans into deliverable multileaf collimator apertures. Step-and-shoot IMRT plans were created for 10 patients with localized prostate cancer using both standard optimization and MCO. Acceptable standard IMRT plans with minimal average rectal dose were chosen for comparison with deliverable MCO plans. The trade-off was, for the MCO plans, managed through a user interface that permits continuous navigation between fluence-based plans. Navigated MCO plans were made deliverable at incremental steps along a trajectory between maximal target homogeneity and maximal rectal sparing. Dosimetric differences between navigated and deliverable MCO plans were also quantified. MCO plans, chosen as acceptable under navigated and deliverable conditions resulted in similar rectal sparing compared with standard optimization (33.7 ± 1.8Gy vs 35.5 ± 4.2Gy, p = 0.117). The dose differences between navigated and deliverable MCO plans increased as higher priority was placed on rectal avoidance. If the best possible deliverable MCO was chosen, a significant reduction in rectal dose was observed in comparison with standard optimization (30.6 ± 1.4Gy vs 35.5 ± 4.2Gy, p = 0.047). Improvements were, however, to some extent, at the expense of less conformal dose distributions, which resulted in significantly higher doses to the bladder for 2 of the 3 tolerance levels. In conclusion, similar IMRT plans can be created for patients with prostate cancer using MCO compared with standard optimization. Limitations exist within MCO regarding conversion of navigated plans to deliverable apertures, particularly for plans that emphasize avoidance of critical structures. Minimizing these differences would result in better quality treatments for patients with prostate cancer who were treated with radiotherapy using MCO plans.

Multiuser Cognitive Relay Networks: Joint Impact of Direct and Relay Communications

In this paper, we propose a multiuser cognitive relay network, where multiple secondary sources communicate with a secondary destination through the assistance of a secondary relay in the presence of secondary direct links and multiple primary receivers. We consider the two relaying protocols of amplify-and-forward (AF) and decode-and-forward (DF), and take into account the availability of direct links from the secondary sources to the secondary destination. With this in mind, we propose an optimal solution for cognitive multiuser scheduling by selecting the optimal secondary source, which maximizes the received signal-to-noise ratio (SNR) at the secondary destination using maximal ratio combining. This is done by taking into account both the direct link and the relay link in the multiuser selection criterion. For both AF and DF relaying protocols, we first derive closed-form expressions for the outage probability and then provide the asymptotic outage probability, which determines the diversity behavior of the multiuser cognitive relay network. Finally, this paper is corroborated by representative numerical examples.

Multimode entanglement and telecloning in a noisy environment

We address the generation, propagation, and application of multipartite continuous variable entanglement in a noisy environment. In particular, we focus our attention on the multimode entangled states achievable by second-order nonlinear crystals-i.e., coherent states of the SU(m,1) group-which provide a generalization of the twin-beam state of a bipartite system. The full inseparability in the ideal case is shown, whereas thresholds for separability are given for the tripartite case in the presence of noise. We find that entanglement of tripartite states is robust against thermal noise, both in the generation process and during propagation. We then consider coherent states of SU(m,1) as a resource for multipartite distribution of quantum information and analyze a specific protocol for telecloning, proving its optimality in the case of symmetric cloning of pure Gaussian states. We show that the proposed protocol also provides the first example of a completely asymmetric 1 -> m telecloning and derive explicitly the optimal relation among the different fidelities of the m clones. The effect of noise in the various stages of the protocol is taken into account, and the fidelities of the clones are analytically obtained as a function of the noise parameters. In turn, this permits the optimization of the telecloning protocol, including its adaptive modifications to the noisy environment. In the optimized scheme the clones' fidelity remains maximal even in the presence of losses (in the absence of thermal noise), for propagation times that diverge as the number of modes increases. In the optimization procedure the prominent role played by the location of the entanglement source is analyzed in details. Our results indicate that, when only losses are present, telecloning is a more effective way to distribute quantum information than direct transmission followed by local cloning.

Nonlinearity Induced Entanglement Stability in a Qubit-Oscillator System

We consider a system composed of a qubit interacting with a quartic (undriven) nonlinear oscillator (NLO) through a conditional displacement Hamiltonian. We show that even a modest nonlinearity can enhance and stabilize the quantum entanglement dynamically generated between the qubit and the NLO. In contrast to the linear case, in which the entanglement is known to oscillate periodically between zero and its maximal value, the nonlinearity suppresses the dynamical decay of the entanglement once it is established. While the entanglement generation is due to the conditional displacements, as noted in several works before, the suppression of its decay is related to the presence of squeezing and other complex processes induced by two- and four-phonon interactions. Finally, we solve the respective Markovian master equation, showing that the previous features are preserved also when the system is open.

Improving signal reliability for indoor off–body communications using spatial diversity at the base station

In this paper, we investigate the potential improvement in signal reliability for indoor off-body communications when using spatial diversity at the base station. In particular, we utilize two hypothetical indoor base stations operating at 5.8 GHz each featuring four antennas which are spaced at either half- or one-wavelength apart. Three on-body locations are considered along with four types of user movement. The cross-correlation between the received signal envelopes observed at each base station antenna element was calculated and found to be always less than 0.5. Selection, maximal ratio, and equal gain combining of the received signal has shown that the greatest improvement is obtained when the user is mobile, with a maximum diversity gain of 11.34 dB achievable when using a four branch receiver. To model the fading envelope obtained at the output of the virtual combiners, we use diversity specific, theoretical probability density functions for multi-branch receivers operating in Nakagami-m fading channels. It is shown that these equations provide an excellent fit to the measured channel data.