Commissioning of a solid tank design for fan-beam optical CT based 3D radiation dosimetry.

Objective.Optical computed tomography (CT) is one of the leading modalities for imaging gel dosimeters used in the verification of complex radiotherapy treatments. In previous work, a novel fan-beam optical CT scanner design was proposed that could significantly reduce the volume of the refractive index baths that are commonly found in optical CT systems. Here, the proposed scanner has been manufactured and commissioned.Approach.Image reconstruction is performed through algebraic reconstruction technique and iterated using the fast iterative shrinkage-thresholding algorithm (FISTA) algorithm. Ray tracing for algebraic reconstruction was performed using an in-house developed ray tracing simulator. A set of Sylgard® 184 phantoms were created to commission spatial resolution, geometric deformity, contrast-to-noise ratio (CNR), and scan settings.Main Results.The scanner is capable of a 0.929 mm-1spatial resolution, observed at 200 iterations, although the spatial resolution is highly dependent on the number of iterations. The geometric distortion, measured by scanning a needle phantom with the prototype scanner as well as a conventional x-ray CT was found to be within <0.25 mm. The CNR was found to peak between 65 and 190 occurring between 50 and 100 iterations and was highly dependent on the region chosen for background noise calculation. The proposed scanner is capable of scanning and reading out slices in less than 1 min per slice.Significance.This work displays the viability of a fan-beam optical CT scanner with minimal index matching using ray-traced algebraic reconstruction.

Optimization of solid tank design for fan-beam optical CT based 3D radiation dosimetry.

Optical computed tomography (CT) is one of the leading modalities for imaging gel dosimeters for 3D radiation dosimetry. There exist multiple scanner designs that have showcased excellent 3D dose verification capabilities of optical CT gel dosimetry. However, due to multiple experimental and reconstruction based factors there is currently no single scanner that has become a preferred standard. A significant challenge with setup and maintenance can be attributed to maintaining a large refractive index bath (1-15 l). In this work, a prototype solid 'tank' optical CT scanner is proposed that minimizes the volume of refractive index bath to between 10 and 35 ml. A ray-path simulator was created to optimize the design such that the solid tank geometry maximizes light collection across the detector array, maximizes the volume of the dosimeter scanned, and maximizes the collected signal dynamic range. An objective function was created to score possible geometries, and was optimized to find a local maximum geometry score from a set of possible design parameters. The design parameters optimized include the block length x bl , bore position x bc , fan-laser position x lp , lens block face semi-major axis length x ma , and the lens block face eccentricity x be . For the proposed design it was found that each of these parameters can have a significant effect on the signal collection efficacy within the scanner. Simulations scores are specific to the attenuation characteristics and refractive index of a simulated dosimeter. It was found that for a FlexyDos3D dosimeter, the ideal values for each of the five variables were: x bl = 314 mm, x bc = 6.5 mm, x lp = 50 mm, x ma = 66 mm, and x be = 0. In addition, a ClearView™ dosimeter was found to have ideal values at: x bl = 204 mm, x bc = 13 mm, x lp = 58 mm, x ma = 69 mm, and x be = 0. The ray simulator can also be used for further design and testing of new, unique and purpose-built optical CT geometries.

Estimation of daily dietary fluoride intake: 3-d food diary v. 2-d duplicate plate.

The 3-d food diary method (3-d FD) or the 2-d duplicate plate (2-d DP) method have been used to measure dietary fluoride (F) intake by many studies. This study aimed to compare daily dietary F intake (DDFI) estimated by the 3-d FD and 2-d DP methods at group and individual levels. Dietary data for sixty-one healthy children aged 4-6 years were collected using 3-d FD and 2-d DP methods with a 1-week gap between each collection. Food diary data were analysed for F using the Weighed Intake Analysis Software Package, whereas duplicate diets were analysed by an acid diffusion method using an F ion-selective electrode. Paired t test and linear regression were used to compare dietary data at the group and individual levels, respectively. At the group level, mean DDFI was 0·025 (sd 0·016) and 0·028 (sd 0·013) mg/kg body weight (bw) per d estimated by 3-d FD and 2-d DP, respectively. No statistically significant difference (P=0·10) was observed in estimated DDFI by each method at the group level. At an individual level, the agreement in estimating F intake (mg/kg bw per d) using the 3-d FD method compared with the 2-d DP method was within ±0·011 (95 % CI 0·009, 0·013) mg/kg bw per d. At the group level, DDFI data obtained by either the 2-d DP method or the 3-d FD method can be replaced. At an individual level, the typical error and the narrow margin between optimal and excessive F intake suggested that the DDFI data obtained by one method cannot replace the dietary data estimated from the other method.

A deterministic model of home and community care client counts in British Columbia.

In British Columbia (BC) Home and Community Care (HCC) services provide a range of health care and support services for British Columbians with acute, chronic, palliative or rehabilitative health care needs. Although it is not surprising that almost 80% of HCC clients are senior citizens (aged 65 and older), this does lead to some concern. In particular, the most recent population projections suggest that the senior population of BC will double in the next twenty years. Predicting how this will impact HCC is of high importance in preparing for future years. In this paper we discuss the development of a deterministic multistate Markov model of the HCC system, its validation, and its predictions for future client counts for various HCC client groupings. This model was originally developed for the BC Ministry of Health Services, and is currently being used as a first step to developing a strategic direction plan for BC's HCC sector. The model makes several notable steps forward in terms of research and modelling of HCC. First, past literature regarding models of HCC appears to be only concerned with publicly funded (government run) residential care environments. Our model advances this in two directions by including at home care and non-publicly funded care. Second, our model considers both the predicted changes in the age demographics of British Columbia, as well as the predicted changes in the relationship between age and health status.

Fate of dietary perchlorate in lactating dairy cows: Relevance to animal health and levels in the milk supply.

Perchlorate is a goitrogenic anion that competitively inhibits the sodium iodide transporter and has been detected in forages and in commercial milk throughout the U.S. The fate of perchlorate and its effect on animal health were studied in lactating cows, ruminally infused with perchlorate for 5 weeks. Milk perchlorate levels were highly correlated with perchlorate intake, but milk iodine was unaffected, and there were no demonstrable health effects. We provide evidence that up to 80% of dietary perchlorate was metabolized, most likely in the rumen, which would provide cattle with a degree of refractoriness to perchlorate. Data presented are important for assessing the environmental impact on perchlorate concentrations in milk and potential for relevance to human health.

Characterization of the bovine innate immune response to intramammary infection with Klebsiella pneumoniae.

Gram-negative bacteria are responsible for almost one-half of the clinical cases of mastitis that occur annually. Of those gram-negative bacteria that induce mastitis, Klebsiella pneumoniae remains one of the most prevalent. Detection of infectious pathogens and the induction of a proinflammatory response are critical components of host innate immunity. The objective of the current study was to characterize several elements of the bovine innate immune response to intramammary infection with Klebsiella pneumoniae. The inflammatory cytokine response and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS)-binding protein (LBP), 2 proteins that contribute to host recognition of gram-negative bacteria, were studied. The contralateral quarters of 7 late-lactating Holstein cows were challenged with either saline or K. pneumoniae, and milk and blood samples were collected. Initial increases in the chemoattractants C5a and IL-8, as well as TNF-alpha, were evident in infected quarters within 16 h of challenge and were temporally coincident with increases in milk somatic cells. Augmented levels of TNF-alpha and IL-8 were observed in infected quarters until >48 h postchallenge, respectively. Elevated levels of IL-12, IFN-gamma, and the antiinflammatory cytokine, IL-10, which were first detected between 12 and 20 h postinfection, persisted in infected quarters throughout the study (>96 h). Initial increases in milk LBP and sCD14 were detected 16 and 20 h, respectively, after challenge. Together, these data demonstrate that intramammary infection with K. pneumoniae elicits a host response characterized by the induction of proinflammatory cytokines and elevation of accessory molecules involved in LPS recognition.

Efficacy and safety of memantine, an NMDA-type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey.

Glutamatergic excitotoxicity has been implicated as a mechanism for injury in a variety of central nervous system pathologies, including glaucoma. Memantine, an NMDA-type glutamatergic open-channel blocker, has pharmacologic properties that make its efficacy greater under excitotoxic conditions, but lesser under normal conditions. Daily oral dosing for approximately 15 months with 4.0 mg/kg memantine in monkeys yielded plasma concentrations similar to those found in patients who received memantine treatment for Parkinson's disease. This same dose of memantine was not associated with any evidence of an effect on the normal function of the retina and central visual pathways, as indicated by measures of the electroretinogram (ERG) and visually-evoked cortical potential (VECP). Amplitude of the VECP response was reduced in eyes with experimentally induced glaucoma. When compared to vehicle-treated control animals, memantine-treated glaucoma eyes suffered significantly less reduction of VECP amplitude. Preliminary results in a rat model for experimental glaucoma also show that, when compared to control animals, systemic treatment with memantine (10 mg/kg/day) was associated with a significant reduction in glaucoma-induced loss of retinal ganglion cells.

Characterization of retinal injury using ERG measures obtained with both conventional and multifocal methods in chronic ocular hypertensive primates.

PURPOSE: To characterize, using both conventional and multifocal electroretinogram (ERG) recordings as well as histologic measures, retinal injury in the chronic ocular hypertensive primate model for experimental glaucoma. METHODS: Ocular hypertension was induced in the right eye of 7 cynomolgous monkeys, Macaca fascicularis, using laser injury to the aqueous outflow tissue at the anterior chamber angle. At 16 months after IOP elevation, ERG recordings were made from both eyes of all animals using both conventional and multifocal methods. After electrophysiological recording, animals were killed and retinal samples were radially sectioned for histologic analysis. RESULTS: Histologic measures showed that ocular hypertensive injury was largely or completely limited to a loss of retinal ganglion cells (RGCs). The degree of RGC loss was similar in central and peripheral retina. Amplitudes of conventional ERG responses were mostly unaffected in eyes having severe loss of RGCs, a finding that is consistent with limited injury to photoreceptors, bipolar cells, and amacrine cells. Peaks in both the first- and second-order multifocal ERG responses were attenuated in ocular hypertensive eyes, and amplitude of these peaks was highly correlated with the density of surviving RGCs. CONCLUSIONS: The results are consistent with a conclusion that both first- and second-order components of the multifocal ERG response from the monkey reflect a significant contribution from activity in RGCs and may provide a useful measure for the clinical diagnosis and management of glaucoma.

Symptomatic lumbar spinal arachnoiditis: fact or fallacy?

It is generally accepted that chronic adhesive lumbar arachnoiditis is a cause of symptoms, notably back pain and/or pain (of almost any type, not necessarily 'anatomical') in the lower limbs, although there is no clearly defined clinical pattern which is clearly associated with this syndrome. There is no doubt that arachnoiditis occurs as a pathological and radiological entity due to a number of causes. In the view of the present authors, the nexus between the pathology and radiology on the one hand, and the patients' symptoms on the other hand, has not been demonstrated with any degree of scientific rigor.

Contribution to the kinetics and amplitude of the electroretinogram b-wave by third-order retinal neurons in the rabbit retina.

The ERG b-wave is widely believed to reflect mainly light-induced activity of on-center bipolar cells and Müller cells. Third-order retinal neurons are thought to contribute negligibly to generation of the b-wave. Here we show that pharmacological agents which affect predominantly third-order neurons alter significantly both the kinetics and amplitude of the b-wave. Our results support the notion that changes in the amplitude and kinetics of light-induced membrane depolarization in third-order neurons produce similar changes in the amplitude and kinetics of the b-wave. We conclude that activity in third-order neurons makes a significant contribution to b-wave generation. Our results also provide evidence that spiking activity of third-order neurons truncates the a-wave by accelerating the onset of the b-wave.

KIDS COUNT: identifying and helping America's most vulnerable.

Using data from the 1999 KIDS COUNT Data Book, compiled and published by The Annie E. Casey Foundation, the most recent state figures (1996) are compared with corresponding data from 1985 to assess the trends in child well-being in each state during the decade. The 10 key indicators used to rank states are taken fro federal government statistical agencies and reflect the best data available for each of the measures. Between 1985 and 1996, child well-being improved across the country in seven of the indicators (infant mortality rate; child death rate; rate of teen death by accidents, homicide and suicide; percent of teens who are high school dropouts; percent of teens not attending school and not working; percent of children living with parents who do not have full-time, year-round employment; and percent of children living in poverty). The three areas of children's well-being that worsened during the time period were; the percent of low birth-weight babies; teen birth rate; and percent of families with children headed by a single parent. While many of America's children have experienced improvements in their well-being, there is a large number of children who have been left behind. The focus of the 1999 KIDS COUNT Date Book is on the 9.2 million children who have been identified as "high risk." These children have four or more family disadvantages that put them at greater risk of experiencing poor outcomes. These kids are not benefiting from the continuing economic boom in the 1990s. The District of Columbia, Louisiana and Mississippi had the largest share of high-risk kids, ranging from 39 to 21 percent of their respective populations, and Utah the lowest, with just 5 percent. Long-term family-centered strategies that are multi-dimensional and community-wide are recommended to help promote family change.

Electrophysiological and histological measures of retinal injury in chronic ocular hypertensive monkeys.

PURPOSE: This study was performed to determine whether components of the standard ERG (electroretinogram), multifocal ERG, and flash VECP (visually-evoked cortical potential) response might provide a sensitive measure of retinal ganglion cell injury in a monkey model for chronic ocular hypertension. METHODS: Argon laser treatment of the aqueous outflow tissue was used to induce chronic elevation of intraocular pressure (IOP) in the right eye of 18 young adult cynomolgous monkeys. At 15 months post- IOP elevation, standard methods were used to record ERG and VECP responses. Multifocal ERG responses were also recorded at this time. Loss of retinal ganglion cells due to ocular hypertensive injury was determined by histological analysis of all retinas. RESULTS: Ocular hypertensive retinal injury was associated with a loss of retinal ganglion cells. There was no histological or electrophysiological evidence for injury to any other retinal cell type. Correlation of electrophysiological response amplitudes with histological measures of retinal ganglion cell loss/survival yielded results which suggest that activity in retinal ganglion cells makes a substantial contribution to components of the 30 Hz flicker ERG, the flash VECP, and both first and second order multifocal ERG responses. Of the electrophysiological measures used in this study, multifocal ERG response amplitude had the greatest sensitivity to retinal ganglion cell loss. CONCLUSIONS: Components of the multifocal ERG provide a sensitive measure of ganglion cell injury in a monkey model of chronic ocular hypertension. These same measures may have utility in the clinical diagnosis and management of glaucoma.

Making kids count.

Using data from the 1988 KIDS COUNT Data Book, compiled and published by The Annie E. Casey Foundation, the most recent state figures (1995) are compared with corresponding data from 1985 to assess the trends in child well-being in each state during the decade. The 10 key indicators used are taken from governmental data sources and reflect the best data available for each of the measures. Between 1985 and 1995, child well-being worsened across the country in five of the indicators, i.e., percent of low birthweight babies; rate of teen deaths by accident, homicide and suicide; teen birth rate; Juvenile Violent Crime Arrest Rate; and percent of families with children headed by a single parent. Areas of improvement include: infant mortality; child death rate; percent of teens who are high school dropouts; and percent of teens not attending school and/or not working. There was no change between 1985 and 1995 in the percent of children living in poverty. When the states are ranked by a composite of the 10 indicators of childhood well-being, a cluster of states in the South and Southwest are at or near the bottom of the rankings while the New England states and those in the upper plains are typically near the top. The states near the top have higher incomes and lower poverty rates than those near the bottom.

Effects of bicarbonate versus HEPES buffering on measured properties of neurons in the salamander retina.

Electrophysiological studies of the isolated retina involve perfusing the tissue with a physiological Ringer's. Organic pH buffers such as HEPES have become increasingly popular in recent years because for many purposes they offer a convenient and reliable alternative to the more traditional bicarbonate/CO2. In this paper, however, we report that important functional properties of rods, bipolar cells, and horizontal cells in the salamander, Ambystoma tigrinum, are sensitive to the choice of buffer and, in the case of horizontal cells, that sensitivity is acute. In bicarbonate/CO2 Ringer's, the dark potential of the horizontal cell was typically near -50 mV and saturating light caused it to hyperpolarize to about -75 mV. On switching to HEPES-buffered Ringer's at the same pH, horizontal cells depolarized in darkness to about -20 mV, close to the chloride equilibrium potential, and the kinetics of their light responses changed. The cone-driven components of light responses increased in size relative to rod-driven components. Saturating lights still hyperpolarized the cells to -75 mV, however. Horizontal cells, being coupled via gap junctions, form a syncytium and syncytial length constants, measured in bicarbonate/CO2 Ringer's, were generally in the range 150-225 microm. On switching to HEPES-buffered Ringer's, length constants increased substantially to 250-330 microm. All these changes were reversible. We discuss our findings within the context of the cell's ability to regulate its internal pH.

Relationship of optic disc topography to optic nerve fiber number in glaucoma.

OBJECTIVE: To assess the relationship between in vivo measurements of optic disc topography and histomorphometric measurements of optic nerve fiber number in glaucoma. METHODS: Both eyes of 10 monkeys (Macaca fascicularis) with laser-induced glaucoma in the right eye were studied. Optic disc topography was measured in vivo with a confocal scanning laser ophthalmoscope. Histomorphometry was performed on optic nerve cross sections using bright-field microscopy with camera lucida. Nerve fiber density was estimated by unbiased random sampling. Nerve fiber number was estimated for each sector by multiplying nerve fiber density with neuroglial area. Nerve fiber count was compared with each of 13 global optic disc topographic parameters. RESULTS: For neuroretinal measurements in the glaucomatous eyes, rim area, retinal nerve fiber layer (RNFL) cross-sectional area, rim volume, and RNFL thickness correlated significantly with optic nerve fiber number. Differences in nerve fiber count between control and glaucomatous optic nerves showed the strongest correlation with differences in mean height contour; this was followed by RNFL cross-sectional area, RNFL thickness, rim volume, and differences in rim area. For cup measurements in the glaucomatous eyes, cup volume below reference, cup area, mean cup depth, the ratio of cup area to disc area, and cup shape correlated significantly with nerve fiber number. Differences in nerve fiber number between control and glaucomatous optic nerves showed the strongest correlation with differences in cup shape; this was followed by mean cup depth, cup volume below reference, the ratio of cup area to disc area, cup area, and differences in cup volume below surface. No association was found between optic nerve fiber number and optic disc area in glaucomatous eyes. CONCLUSIONS: In experimental glaucoma, most optic disc topography measures correlated significantly with optic nerve fiber number. The results of this histomorphometric study support the use of confocal scanning laser ophthalmoscopy to evaluate optic nerve damage in glaucoma.