Drug and light delivery strategies for photodynamic antimicrobial chemotherapy (PACT) of pulmonary pathogens:a pilot study

Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF) suffers, with multidrug-resistant Pseudomonas aeruginosa and Burkholderia cepacia complex as problematic pathogens in terms of recurrent and unremitting infections. Novel treatment of pulmonary infection is required to improve the prognosis and quality of life for chronically infected patients. Photodynamic antimicrobial chemotherapy (PACT) is a treatment combining exposure to a light reactive drug, with light of a wavelength specific for activation of the drug, in order to induce cell death of bacteria. Previous studies have demonstrated the susceptibility of CF pathogens to PACT in vitro. However, for the treatment to be of clinical use, light and photosensitizer must be able to be delivered successfully to the target tissue. This preliminary study assessed the potential for delivery of 635 nm light and methylene blue to the lung using an ex vivo and in vitro lung model. Using a fibre-optic light delivery device coupled to a helium-neon laser, up to 11% of the total light dose penetrated through full thickness pulmonary parenchymal tissue, which indicates potential for multiple lobe irradiation in vivo. The mass median aerodynamic diameter (MMAD) of particles generated via methylene blue solution nebulisation was 4.40 µm, which is suitable for targeting the site of infection within the CF lung. The results of this study demonstrate the ability of light and methylene blue to be delivered to the site of infection in the CF lung. PACT remains a viable option for selective killing of CF lung pathogens.

On the brightness distribution of type ia supernovae from violent white dwarf mergers

We investigate the brightness distribution expected for thermonuclear explosions that might result from the ignition of a detonation during the violent merger of white dwarf (WD) binaries. Violent WD mergers are a subclass of the canonical double degenerate scenario where two carbon-oxygen (CO) WDs merge when the larger WD fills its Roche lobe. Determining their brightness distribution is critical for evaluating whether such an explosion model could be responsible for a significant fraction of the observed population of Type Ia supernovae (SNe Ia). We argue that the brightness of an explosion realized via the violent merger model is mainly determined by the mass of Ni produced in the detonation of the primary COWD. To quantify this link, we use a set of sub-Chandrasekhar mass WD detonation models to derive a relationship between primary WD mass (m) and expected peak bolometric brightness (M). We use this m-M relationship to convert the masses of merging primary WDs from binary population models to a predicted distribution of explosion brightness. We also investigate the sensitivity of our results to assumptions about the conditions required to realize a detonation during violent mergers ofWDs. We find a striking similarity between the shape of our theoretical peak-magnitude distribution and that observed for SNe Ia: our model produces a M distribution that roughly covers the range and matches the shape of the one observed for SNe Ia. However, this agreement hinges on a particular phase of mass accretion during binary evolution: the primary WD gains ~0.15-0.35M? from a slightly evolved helium star companion. In our standard binary evolution model, such an accretion phase is predicted to occur for about 43 per cent of all binary systems that ultimately give rise to binary CO WD mergers. We also find that with high probability, violent WD mergers involving the most massive primaries (?1.3M?, which should produce bright SNe) have delay times ?500 Myr. © 2012 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.

Electroencephalographic Activity in Response to Procedural Pain in Preterm Infants Born at 28 and 33 Weeks Gestational Age

OBJECTIVES:: Preterm infants undergo frequent painful procedures in the neonatal intensive care unit. Electroencephalography (EEG) changes in reaction to invasive procedures have been reported in preterm and full-term neonates. Frontal EEG asymmetry as an index of emotion during tactile stimulation shows inconsistent findings in full-term infants, and has not been examined in the context of pain in preterm infants. Our aim was to examine whether heel lance for blood collection induces changes in right-left frontal asymmetry, suggesting negative emotional response, in preterm neonates at different gestational age (GA) at birth and different duration of stay in the neonatal intensive care unit. MATERIALS AND METHODS:: Three groups of preterm infants were compared: set 1: group 1 (n=24), born and tested at 28 weeks GA; group 2 (n=22), born at 28 weeks GA and tested at 33 weeks; set 2: group 3 (n=25), born and tested at 33 weeks GA. EEG power was calculated for 30-second artifact-free periods, in standard frequency bandwidths, in 3 phases (baseline, up to 5 min after heel lance, 10 min after heel lance). RESULTS:: No significant differences were found in right-left frontal asymmetry, or in ipsilateral or contralateral somatosensory response, across phases. In contrast, the Behavioral Indicators of Infant Pain scores changed across phase (P

Magnetoencephalography reveals slowing of resting peak oscillatory frequency in children born very preterm

Resting cortical activity is characterized by a distinct spectral peak in the alpha frequency range. Slowing of this oscillatory peak toward the upper theta-band has been associated with a variety of neurological and neuropsychiatric conditions and has been attributed to altered thalamocortical dynamics. Children born very preterm exhibit altered development of thalamocortical systems. To test the hypothesis that peak oscillatory frequency is slowed in children born very preterm, we recorded resting magnetoencephalography (MEG) from school age children born very preterm (= 32 wk gestation) without major intellectual or neurological impairment and age-matched full-term controls. Very preterm children exhibit a slowing of peak frequency toward the theta-band over bilateral frontal cortex, together with reduced alpha-band power over bilateral frontal and temporal cortex, suggesting that mildly dysrhythmic thalamocortical interactions may contribute to altered spontaneous cortical activity in children born very preterm.

Altered Long-Range Phase Synchronization and Cortical Activation in Children Born Very Preterm

Children born very preterm, even with broadly normal IQ, commonly show selective difficulties in visuospatial processing and executive functioning. Very little, however, is known what alterations in cortical processing underlie these deficits. We recorded MEG while eight children born very preterm (=32 weeks gestational age) and eight full-term controls performed a visual short-term memory task at mean age 7.5 years (range 6.4 - 8.4). Previously, we demonstrated increased long-range alpha and beta band phase synchronization between MEG sensors during STM retention in a group of 17 full-term children age 6-10 years. Here we present preliminary evidence that long-range phase synchronization in very preterm children, relative to controls, is reduced in the alpha-band but increased in the theta-band. In addition, we investigated cortical activation during STM retention employing synthetic aperture magnetometry (SAM) beamformer to localize changes in gamma-band power. Preliminary results indicate sequential activation of occipital, parietal and frontal cortex in control children, as well as reduced activation in very preterm children relative to controls. These preliminary results suggest that children born very preterm exhibit altered inter-regional functional connectivity and cortical activation during cognitive processing.

Long-range synchronization and local desynchronization of alpha oscillations during visual short-term memory retention in children

Local alpha-band synchronization has been associated with both cortical idling and active inhibition. Recent evidence, however, suggests that long-range alpha synchronization increases functional coupling between cortical regions. We demonstrate increased long-range alpha and beta band phase synchronization during short-term memory retention in children 6-10 years of age. Furthermore, whereas alpha-band synchronization between posterior cortex and other regions is increased during retention, local alpha-band synchronization over posterior cortex is reduced. This constitutes a functional dissociation for alpha synchronization across local and long-range cortical scales. We interpret long-range synchronization as reflecting functional integration within a network of frontal and visual cortical regions. Local desynchronization of alpha rhythms over posterior cortex, conversely, likely arises because of increased engagement of visual cortex during retention.

Bilateral non-contiguous atypical papillary glioneuronal tumor:case report

Papillary glioneuronal tumor (PGNT) was first described as a distinct clinic-pathological entity by Komori et al. in 1998. Since then it has been included as a mixed neuronal-glial tumor in the revised WHO (2007) classification of central nervous system tumors. On brain imaging, it appears as a demarcated, solid to cystic, contrast-enhancing mass usually located in the temporal lobe. Histologically, it is considered a biphasic tumor characterized by small cuboidal GFAP-positive astrocytes around hyalinised blood vessels and synaptophysin-positive interpapillary collections of neurocytes, large neurons and intermediate-sized "ganglioid cells". Although they are generally regarded as benign WHO Grade I tumors, recent reports have described more pathologically aggressive features. To date, these reports have all been single lesions.

Bilateral non-contiguous atypical papillary glioneuronal tumor: case report

Papillary glioneuronal tumor (PGNT) was first described as a distinct clinic-pathological entity by Komori et al. in 1998. Since then it has been included as a mixed neuronal-glial tumor in the revised WHO (2007) classification of central nervous system tumors. On brain imaging, it appears as a demarcated, solid to cystic, contrast-enhancing mass usually located in the temporal lobe. Histologically, it is considered a biphasic tumor characterized by small cuboidal GFAP-positive astrocytes around hyalinised blood vessels and synaptophysin-positive interpapillary collections of neurocytes, large neurons and intermediate-sized "ganglioid cells". Although they are generally regarded as benign WHO Grade I tumors, recent reports have described more pathologically aggressive features. To date, these reports have all been single lesions.

Abnormal changes in voltage-gated sodium channels NaV1.1, NaV1.2, NaV1.3, NaV1.6 and in Calmodulin/calmodulin-dependent protein kinase II, within the brains of spontaneously epileptic rats and tremor rats

Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. The expressions of different VGSCs subtypes are varied in diverse animal models of epilepsy that may reflect their multiple phenotypes or the complexity of the mechanisms of epilepsy. In a previous study, we reported that NaV1.1 and NaV1.3 were up-regulated in the hippocampus of the spontaneously epileptic rat (SER). In this study, we further analyzed both the expression and distribution of the typical VGSC subtypes NaV1.1, NaV1.2, NaV1.3 and NaV1.6 in the hippocampus and in the cortex of the temporal lobe of two genetic epileptic animal models: the SER and the tremor rat (TRM). The expressions of calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMKII) were also analyzed with the purpose of assessing the effect of the CaM/CaMKII pathway in these two models of epilepsy. Increased expression of the four VGSC subtypes and CaM, accompanied by a decrease in CaMKII was observed in the hippocampus of both the SERs and the TRM rats. However, the changes observed in the expression of VGSC subtypes and CaM were decreased with an elevated CaMKII in the cortex of their temporal lobes. Double-labeled immunofluorescence data suggested that in SERs and TRM rats, the four subtypes of the VGSC proteins were present throughout the CA1, CA3 and dentate gyrus regions of the hippocampus and temporal lobe cortex and these were co-localized in neurons with CaM. These data represent the first evidence of abnormal changes in expression of four VGSC subtypes (NaV1.1, NaV1.2, NaV1.3 and NaV1.6) and CaM/CaMKII in the hippocampus and temporal lobe cortex of SERs and TRM rats. These changes may be involved in the generation of epileptiform activity and underlie the observed seizure phenotype in these rat models of genetic epilepsy.

GIANT LOBES OF CENTAURUS A RADIO GALAXY OBSERVED WITH THE SUZAKU X-RAY SATELLITE

We report on Suzaku observations of selected regions within the southern giant lobe of the radio galaxy Centaurus A. In our analysis we focus on distinct X-ray features detected with the X-ray Imaging Spectrometer within the range 0.5-10 keV, some of which are likely associated with fine structure of the lobe revealed by recent high-quality radio intensity and polarization maps. With the available photon statistics, we find that the spectral properties of the detected X-ray features are equally consistent with thermal emission from hot gas with temperatures kT > 1 keV, or with a power-law radiation continuum characterized by photon indices Gamma similar to 2.0 +/- 0.5. However, the plasma parameters implied by these different models favor a synchrotron origin for the analyzed X-ray spots, indicating that a very efficient acceleration of electrons up to greater than or similar to 10 TeV energies is taking place within the giant structure of Centaurus A, albeit only in isolated and compact regions associated with extended and highly polarized radio filaments. We also present a detailed analysis of the diffuse X-ray emission filling the whole field of view of the instrument, resulting in a tentative detection of a soft excess component best fitted by a thermal model with a temperature of kT similar to 0.5 keV. The exact origin of the observed excess remains uncertain, although energetic considerations point to thermal gas filling the bulk of the volume of the lobe and mixed with the non-thermal plasma, rather than to the alternative scenario involving a condensation of the hot intergalactic medium around the edges of the expanding radio structure. If correct, this would be the first detection of the thermal content of the extended lobes of a radio galaxy in X-rays. The corresponding number density of the thermal gas in such a case is n(g) similar to 10(-4) cm(-3), while its pressure appears to be in almost exact equipartition with the volume-averaged non-thermal pressure provided by the radio-emitting electrons and the lobes' magnetic field. A prominent large-scale fluctuation of the Galactic foreground emission, resulting in excess foreground X-ray emission aligned with the lobe, cannot be ruled out. Although tentative, our findings potentially imply that the structure of the extended lobes in active galaxies is likely to be highly inhomogeneous and non-uniform, with magnetic reconnection and turbulent acceleration processes continuously converting magnetic energy to internal energy of the plasma particles, leading to possibly significant spatial and temporal variations in the plasma beta parameter around the volume-averaged equilibrium condition beta similar to 1.

CP retrodirective antenna array performance degradation at large elevation angles

At large elevation angles away from boresight the performance of planar phased antenna arrays for circularly polarized, CP, signals suffers from significant gain reduction, worsening of the circular polarization purity, increased pointing error and unwanted dominantly specular lobe radiation. The mechanisms governing this performance deterioration and suggestions for possible rectification are for the first time elaborated in this paper. The points raised in this paper are important when CP retrodirective arrays are to be deployed in self-tracking satellite and terrestrial communication systems mounted on mobile platforms.

Molecularly Imprinted Polymers for Corticosteroids: Impact of polymer format on recognition behaviour

A comparative study of different polymeric formats for the targeting of corticosteroids, focusing on the use of bulk monolith and precipitation polymerisation strategies, was performed and the effect on recognition behaviour was studied. Hydrocortisone-17-butyrate was selected as the template and methacrylic acid as the functional monomer, following 1H NMR investigation of the pre-polymerisation mixture. Three different cross-linkers were tested, ranging from moderate to highly hydrophobic. The synthesised bulk and precipitated imprinted polymers were physically characterised by nitrogen sorption and evaluated by means of HPLC and frontal chromatography against a range of template analogues. While some degree of selectivity for the template was achieved for all tested polymers, the ones based on the tri-functional cross-linking monomer TRIM exhibited the longest retention for all corticosteroids, especially in the precipitated format, which suggested 31 broader group selectivity.

Roche Tomography of the Secondary Stars in CVS

The secondary stars in cataclysmic variables (CVs) are key to our understanding of the origin evolution and behaviour of this class of interacting binary. In seeking a fuller understanding of these objects the challenge for observers is to obtain images of the secondary star. This goal can be achieved through Roche tomography an indirect imaging technique that can be used to map the Roche-lobe-filling secondary star. The review begins with a description of the basic principles that underpin Roche tomography including methods for determining the binary system parameters. Noise propagation onto Roche tomograms is also covered. Finally the review concludes with a look at the main scientific highlights to date and the future prospects for Roche tomography

Discriminating Taxonomic Categories and Domains in Mental Simulations of Concepts of Varying Concreteness

Most studies of conceptual knowledge in the brain focus on a narrow range of concrete conceptual categories, rely on the researchers' intuitions about which object belongs to these categories, and assume a broadly taxonomic organization of knowledge. In this fMRI study, we focus on concepts with a variety of concreteness levels; we use a state of the art lexical resource (WordNet 3.1) as the source for a relatively large number of category distinctions and compare a taxonomic style of organization with a domain-based model (associating concepts with scenarios). Participants mentally simulated situations associated with concepts when cued by text stimuli. Using multivariate pattern analysis, we find evidence that all Taxonomic categories and Domains can be distinguished from fMRI data and also observe a clear concreteness effect: Tools and Locations can be reliably predicted for unseen participants, but less concrete categories (e.g., Attributes, Communications, Events, Social Roles) can only be reliably discriminated within participants. A second concreteness effect relates to the interaction of Domain and Taxonomic category membership: Domain (e.g., relation to Law vs. Music) can be better predicted for less concrete categories. We repeated the analysis within anatomical regions, observing discrimination between all/most categories in the left middle occipital and temporal gyri, and more specialized discrimination for concrete categories Tool and Location in the left precentral and fusiform gyri, respectively. Highly concrete/abstract Taxonomic categories and Domain were segregated in frontal regions. We conclude that both Taxonomic and Domain class distinctions are relevant for interpreting neural structuring of concrete and abstract concepts.

Neural correlates of task switching in paternal 15q11-q13 deletion Prader-Willi syndrome

We report a first study of brain activity linked to task switching in individuals with Prader-Willi syndrome (PWS) PWS individuals show a specific cognitive deficit in task switching which may be associated with the display of temper outbursts and repetitive questioning The performance of participants with PWS and typically developing controls was matched in a cued task switching procedure and brain activity was contrasted on switching and non switching blocks using SARI Individuals with PWS did not show the typical frontal-parietal pattern of neural activity associated with switching blocks, with significantly reduced activation in regions of the posterior parietal and ventromedial prefrontal cortices We suggest that this is linked to a difficulty in PWS in setting appropriate attentional weights to enable task set reconfiguration In addition to this, PWS individuals did not show the typical pattern of deactivation, with significantly less deactivation in an anterior region of the ventromedial prefrontal cortex One plausible explanation for this is that individuals with PWS show dysfunction within the default mode network which has been linked to attentional control The data point to functional changes in the neural circuitry supporting task switching in PWS even when behavioural performance is matched to controls and thus highlight neural mechanisms that may be involved in a specific pathway between genes cognition and behaviour (C) 2010 Elsevier B V All rights reserved