Evaluation of an x-ray CT polymer gel dosimetry system in the measurement of deformed dose.

This study is an evaluation of the use of a N-isopropylacrylamide (NIPAM)-based x-ray CT polymer gel dosimetry (PGD) system in the measurement of deformed dose. This work also compares dose that is measured by the gel dosimetry system to dose calculated by a novel deformable dose accumulation algorithm, defDOSXYZnrc, that uses direct voxel tracking. Deformable gels were first irradiated using a single 3.5 × 5 cm2 open field and the static dose was compared to defDOSXYZnrc as a control measurement. Gel measurement was found to be in excellent agreement with defDOSXYZnrc in the static case with gamma passing rates of 94.5% using a 3%/3 mm criterion and 93.3% using a 3%/2 mm criterion. Following the static measurements, a deformable gel was irradiated with the same single field under an external compression of 25 mm and then released from this compression for dosimetric read out. The measured deformed dose was then compared to deformed dose calculated by defDOSXYZnrc based on deformation vectors produced by the Velocity AI deformable image registration (DIR) algorithm. In the deformed dose distribution there were differences in the measured and calculated field position of up to 0.8 mm and differences in the measured in calculated field size of up to 11.9 mm. Gamma pass rates were 60.0% using a 3%/3 mm criterion and 56.8% using a 3%/2 mm criterion for the deforming measurements representing a decrease in agreement compared to the control measurements. Further analysis showed that passing rates increased to 86.5% using a 3%/3 mm criterion and 70.5% using a 3%/2 mm criterion in voxels within 5 mm of fiducial markers used to guide the deformable image registration. This work represents the first measurement of deformed dose using x-ray CT polymer gel dosimetry. Overall these results highlight some of the challenges in the calculation and measurement of deforming dose and provide insight into possible strategies for improvement.

Linac-integrated kV-cone beam CT polymer gel dosimetry.

X-ray CT polymer gel dosimetry (PGD) remains a promising tool for three dimensional verification of high-dose treatment deliveries such as non-coplanar stereotactic irradiations. Recent demonstrations have shown a proof-of-principle application of linac-integrated cone beam CT-imaged (LI-CBCT) PGDs for 3D dose verification. LI-CBCT offers advantages over previous CT based PGD, including close to real-time imaging of the irradiated dosimeter, as well as the ability to maintain the dosimeter in the same physical location for irradiation and imaging, thereby eliminating spatial errors due to dosimeter re-positioning for read-out that may occur for other systems. However the dosimetric characteristics of a LI-CBCT PGD system remain to be established. The work herein determines the dosimetric properties and critical parameters needed to perform cone beam PGD. In particular, we show that imaging the dosimeter 20-30 min post irradiation offers excellent recovery of maximum polymerization yield ([Formula: see text]90%), averaging with as few as 10 image averages can provide ∼90% gamma pass rates (3%, 3 mm) as compared to treatment planning, and that eliminating outlier averaging points can improve the precision and signal to noise ratio of resultant images. In summary, with appropriate methodology LI-CBCT PGD can provide dosimetric data capable of verification of complex high dose radiation deliveries in three dimensions and may find use in commissioning and validation of novel complex treatments.

Introduction of a deformable x-ray CT polymer gel dosimetry system.

This study introduces the first 3D deformable dosimetry system based on x-ray computed tomography (CT) polymer gel dosimetry and establishes the setup reproducibility, deformation characteristics and dose response of the system. A N-isopropylacrylamide (NIPAM)-based gel formulation optimized for x-ray CT gel dosimetry was used, with a latex balloon serving as the deformable container and low-density polyethylene and polyvinyl alcohol providing additional oxygen barrier. Deformable gels were irradiated with a 6 MV calibration pattern to determine dosimetric response and a dosimetrically uniform plan to determine the spatial uniformity of the response. Wax beads were added to each gel as fiducial markers to track the deformation and setup of the gel dosimeters. From positions of the beads on CT images the setup reproducibility and the limits and reproducibility of gel deformation were determined. Comparison of gel measurements with Monte Carlo dose calculations found excellent dosimetric accuracy, comparable to that of an established non-deformable dosimetry system, with a mean dose discrepancy of 1.5% in the low-dose gradient region and a gamma pass rate of 97.9% using a 3%/3 mm criterion. The deformable dosimeter also showed good overall spatial dose uniformity throughout the dosimeter with some discrepancies within 20 mm of the edge of the container. Tracking of the beads within the dosimeter found that sub-millimetre setup accuracy is achievable with this system. The dosimeter was able to deform and relax when externally compressed by up to 30 mm without sustaining any permanent damage. Internal deformations in 3D produced average marker movements of up to 12 mm along the direction of compression. These deformations were also shown to be reproducible over 100 consecutive deformations. This work has established several important characteristics of a new deformable dosimetry system which shows promise for future clinical applications, including the validation of deformable dose accumulation algorithms.

Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma.

Understanding how RhoC expression and activation are regulated is essential for deciphering its contribution to tumorigenesis. Here, we report that RhoC expression and activation are induced by the epithelial to mesenchymal transition (EMT) of colon carcinoma. Using LIM 1863 colon cancer cells, RhoC protein expression and subsequent activation were detected coincident with the loss of E-cadherin and acquisition of mesenchymal characteristics. Several Ets-1 binding sites were identified in the RhoC promoter, and evidence was obtained using chromatin immunoprecipitation that Ets-1 can regulate RhoC expression during the EMT. Interestingly, a marked decrease in RhoA activation associated with the EMT was observed that corresponds to the increase in RhoC expression. Use of shRNA established that RhoA inhibits and RhoC promotes post-EMT cell migration, demonstrating functional significance for their coordinate regulation. To assess the importance of RhoC expression in colon cancer, immunohistochemistry was performed on 566 colorectal tumors with known clinical outcome. The level of RhoC ranged from no expression to high expression, and statistical analysis revealed that elevated RhoC expression correlates with poor outcome as well as aberrant expression and localization of E-cadherin. These data provide one mechanism for how RhoC expression is regulated in colon carcinoma and substantiate its utility as a prognostic marker.

Consumption of untreated tank rainwater and gastroenteritis among young children in South Australia.

BACKGROUND: Tank rainwater is a source of untreated drinking water in Australia and elsewhere. The aim of this study was to determine whether the risk of gastroenteritis among children who drank tank rainwater differed from that of children who drank treated public mains water. METHODS: A cohort study of 1,016 4- to 6-year old children who drank rainwater or treated mains water in rural South Australia was undertaken in 1999. Parents kept a daily diary of their child's gastrointestinal symptoms and water consumption for a period of 6 weeks. Data on respiratory illness and other risk factors for gastroenteritis were also collected. RESULTS: The incidence of gastroenteritis among children was 3.8-5.3 episodes per child-year, but most episodes (60%) lasted just 1 day. No increase in odds of gastroenteritis was observed among children who drank rainwater compared with treated mains water. The adjusted odds ratio for gastroenteritis associated with rainwater consumption compared with mains consumption was 0.84 (95% confidence interval 0.63-1.13). CONCLUSIONS: Gastroenteritis was found to be a significant cause of morbidity among young children. Young children, who were regular consumers of tank rainwater, were at no greater odds of gastroenteritis than those who drank treated public mains water.

Neuronal interactions improve cortical population coding of movement direction.

Interactions among groups of neurons in primary motor cortex (MI) may convey information about motor behavior. We investigated the information carried by interactions in MI of macaque monkeys using a novel multielectrode array to record simultaneously from 12-16 neurons during an arm-reaching task. Pairs of simultaneously recorded cells revealed significant correlations in their trial-to-trial firing rate variation when estimated over broad (600 msec) time intervals. This covariation was only weakly related to the preferred directions of the individual MI neurons estimated from the firing rate and did not vary significantly with interelectrode distance. Most significantly, in a portion of cell pairs, correlation strength varied with the direction of the arm movement. We evaluated to what extent correlated activity provided additional information about movement direction beyond that available in single neuron firing rate. A multivariate statistical model successfully classified direction from single trials of neural data. However, classification was consistently better when correlations were incorporated into the model as compared to one in which neurons were treated as independent encoders. Information-theoretic analysis demonstrated that interactions caused by correlated activity carry additional information about movement direction beyond that based on the firing rates of independently acting neurons. These results also show that cortical representations incorporating higher order features of population activity would be richer than codes based solely on firing rate, if such information can exploited by the nervous system.

Candida antigen detection in two premature neonates with disseminated candidiasis.

Two premature neonates with birth weight less than 1,200 g developed systemic candidiasis during treatment with multiple antibiotics and parenteral hyperalimentation. Clinical findings included signs of necrotizing enterocolitis in one patient and multiple fungal renal cortical abscesses in the other. The Candida antigen, mannan, was present in the sera of both patients at the time of clinical deterioration. Multiple blood cultures and urine and stool samples from both patients grew Candida albicans. Systemic antifungal therapy was given for a 6-week period and was associated with prolonged antigenemia despite negative findings on follow-up cultures. Antifungal therapy was stopped soon after antigen was no longer detected. Both patients recovered without evidence of further fungal infection. Candida antigen detection may be useful in the diagnosis and follow-up of premature infants with disseminated candidiasis.

A technique to prevent dural adhesions to chronically implanted microelectrode arrays.

Minimizing relative movements between neural tissues and arrays of microelectrodes chronically implanted into them is expected to greatly enhance the capacity of the microelectrodes to record from single cortical neurons on a long-term basis. We describe a new surgical technique to minimize the formation of adhesions between the dura and an implanted electrode array using a 12 microm (0.5 mil) thick sheet of Teflon film positioned between the array and the dura. A total of 15 cats were implanted using this technique. Gross examination of 12 implant sites at the time of sacrifice failed to find evidence of adhesions between the arrays and the dura when the Teflon(R) film remained in its initial position. In six implants from which recordings were made, an average of nine of the 11 (81%) connected electrodes in each array recorded evoked neural activity after 180 days post implantation. Further, on average, two separable units were identified on each of the implanted electrodes in these arrays. No significant change was found in the density of cell bodies around implanted electrodes of four of the implanted electrode arrays. However, histological evaluation of the implant sites revealed evidence of meningeal proliferation beneath the arrays. The technique described is shown to be effective at preventing adhesions between implanted electrode arrays and improve the characteristics of chronic recordings obtained with these structures.

Localization of monoamine fluorescence in the stomatogastric nervous system of lobsters.

Explorations into the crustacean stomatogastric nervous system have focused on the stomatogastric ganglion as a paradigm of neural mechanisms and integrative circuitry. Emerging evidence implicates dopamine as a fundamental modulator of the bursting pacemaker neurons and many of the intraganglionic rhythms. The present paper has employed formaldehyde-induced fluorescence in freeze-dried specimens, a microscopic histochemical technique which demonstrates anatomical structures containing particular putative transmitters, indoleamines and catecholamines. We have localized specific, formaldehyde-induced fluorescence in the lobster stomatogastric nervous system. This fluorescence occurs throughout the stomatogastric ganglion neuropil, in 4-8 cell bodies of the bilaterally paired commissural ganglia and in discrete and continuous neurites interconnecting these 3 ganglia. Variations of the basic fluorescence technique suggest that the specific fluorescence is catecholaminergic. Evidence from related biochemical studies supports this observation and indicates that the catecholaminergic fluorescence is dopaminergic since tests for norepinephrine are negative while concomitant tests for dopamine are positive.

Single unit recording capabilities of a 100 microelectrode array.

We have developed a three-dimensional silicon electrode array which provides 100 separate channels for neural recording in cortex. The device is manufactured using silicon micromachining techniques, and we have conducted acute recording experiments in cat striate cortex to evaluate the recording capabilities of the array. In a series of five acute experiments, 58.6% of the electrodes in the array were found to be capable of recording visually evoked responses. In the most recent acute study, the average signal-to-noise ratio for recordings obtained from 56 of the electrodes in the array was calculated to be 5.5:1. Using standard window discrimination techniques, an average of 3.4 separable spikes were identified for each of these electrodes. In order to compare the two-dimensional mapping capabilities of the array with those derived from other technologies, orientation preference and ocular dominance maps were generated for each of the evoked responses. Histological evaluation of the implant site indicates some localized tissue insult, but this is likely due to the perfusion procedure since high signal-to-noise ratio neural responses were recorded. The recording capabilities of the Utah Intracortical Electrode Array in combination with the large number of electrodes available for recording make the array a tool well suited for investigations into the parallel processing mechanisms in cortex.

A neural interface for a cortical vision prosthesis.

The development of a cortically based vision prosthesis has been hampered by a lack of basic experiments on phosphene psychophysics. This basic research has been hampered by the lack of a means to safely stimulate large numbers of cortical neurons. Recently, a number of laboratories have developed arrays of silicon microelectrodes that could enable such basic studies on phosphene psychophysics. This paper describes one such array, the Utah electrode array, and summarizes neurosurgical, physiological and histological experiments that suggest that such an array could be implanted safely in visual cortex. We also summarize a series of chronic behavioral experiments that show that modest levels of electrical currents passed into cortex via this array can evoke sensory percepts. Pending the successful outcome of biocompatibility studies using such arrays, high count arrays of penetrating microelectrodes similar to this design could provide a useful tool for studies of the psychophysics of phosphene perception in human volunteers. Such studies could provide a proof-of-concept for cortically based artificial vision.

Serotonergic innervation of the rat caudate following a neonatal 6-hydroxydopamine lesion: an anatomical, biochemical and pharmacological study.

6-Hydroxydopamine (6-OHDA) treatment of neonatal rats resulted in a dose-related loss of striatal dopamine (DA). These reductions corresponded closely with the loss of tyrosine hydroxylase-containing terminals at this brain site. Striatal serotonin (5-HT) concentration increased only after DA was maximally depleted by the highest dose of 6-OHDA. Quantitative immunohistochemistry revealed that the increased 5-HT content after neonatal 6-OHDA lesioning was due to a proliferation of 5-HT nerve terminals. The density of immunoreactive 5-HT-containing terminals appeared to increase more than did the 5-HT content. The present study examined whether 5-HT hyperinnervation was playing a role in behavioral responses induced by D1-DA agonists and antagonists in neonatally lesioned rats, because reports have suggested that these drugs may interact with 5-HT receptors. However, SCH-23390, the D1-DA antagonist (0.3 mg/kg), did not alter behavioral responses to 5-HTP and SKF-38393 (3 mg/kg), a D1-DA agonist did not produce any signs of activating 5-HT receptors in 5,7-DHT-lesioned rats. These data indicate that these compounds affecting D1-DA receptors do not have a significant effect on 5-HT function at doses which have maximal effects on D1-DA receptor function. Pretreatment with the 5-HT antagonist methysergide did not produce a change in apomorphine-induced locomotion and did not antagonize the self-mutilation or the other behaviors produced by L-DOPA or SKF-38393 in neonatally lesioned rats, suggesting that 5-HT hyperinnervation is not responsible for these drug-induced changes in neonatal 6-OHDA-lesioned rats.

Electron microscopy of stomatogastric ganglion in the lobster Homarus americanus.

The stomatogastric ganglion and two of the associated afferent and efferent nerve trunks (stomatogastric and dorsal ventricular nerves) from Homarus americanus have been examined with light and electron microscopy after glutaraldehyde-osmium tetroxide fixation. The dorsally located neuron somata, rich in ribosomes and glycogen, are encased in multi-layered glial and fibrous sheaths. The synaptic neuropil regions occur scattered throughout the central and ventral part of the ganglion, interspersed amonglarger nerve fibres of extrinsic and intrinsic origin from which the neuropil is derived. Neural processes containing masses of small clear vesicles plus larger dense-core vesicles make apparent synaptic contacts at points of increased membrane density with smaller, non-vesicle-containing or sometimes other vesicle-containing nerve fibres.

Microscopic localization of cholinesterases in the nervous systems of the lobsters, Panulirus argus and Homarus americanus.

Using acetylthiocholine as substrate, microscopically localizable cholinesterase (ChE) activity is demonstrated in neural and glial elements of central and peripheral nervous systems of the lobsters, Panulirus argus and Homarus americanus. Moderate to very intense ChE activity occurs in all synaptic regions of the central ganglia and stomatogastric ganglion, in glial sheaths around neuron somata and peripheral nerve axons, and in cytoplasm of a few nerve cell bodies. Axons, identified as motor, contain extremely little ChE. The principal reaction in peripheral nerves occurs in sheath elements of sensory fibres; in most cases, much of the reaction is lost as the nerves lose the sheaths at the point of entry into brain.

Head louse infection: a health promotion activity.

Head lice are the most common human ectoparasite. Although an infectious disease, louse infection rarely cause physical problems other than an itchy scalp. Social stigma surrounding infection induces feelings of shame, anger and embarrassment for families. Preventative health education and promotion via screening can effectively reduce the incidences of lice infection. The Mosaic Model of Treatment is recommended as the most up-to-date treatment regime, suitable for use on all children.