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Biomedical subjects

R W Anderson

Publications and source records attributed to R W Anderson.

At least 19 recordsLinked to original sources

Classification of events with an off-site radiological impact at the Sellafield site between 1950 and 2000, using the International Nuclear Event Scale.

The paper assesses unplanned operational events at the Sellafield nuclear installation, formerly Windscale and Calder Works, in Cumbria, England, over the period 1950-2000 that had, or could have had, radiological implications for members of the general public. A unified system of off-site impact rating has been developed using a site-specific application of the International Nuclear Event Scale (INES) that is applied retrospectively to events since the start of operations at the site in 1950. Published and unpublished sources of information have been used to assemble what the authors believe to be a complete list of events over the period that would now be assessed as INES level 3 or above on the basis of off-site impact. The last such event occurred in 1984. The exercise also demonstrates that it is possible to apply the current INES rating scheme to a wide variety of radiological events.

Environmental Exposure↗

Big bacteria pass through very small holes.

Can normal-sized bacteria pass through small holes, and if so how? We have found that common, potentially pathogenic, bacteria (which are nominally larger than 0.2 microm) can cross a 0.2 microm nylon membrane. All of the bacteria crossed from the upper membrane surface to the solid medium below the membrane; this ability was highly repeatable and did not depend on the make of membrane used. Bacteria growing below the membrane exhibited normal size and morphology. We suggest that the ability of common bacteria to pass through small holes has important implications in relation to their role as pathogens.

Bacterial Physiological Phenomena↗

Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States.

The level of contamination by antineoplastic agents in drug preparation and administration areas in cancer treatment centers in Canada and the United States was determined. Sampling locations at three cancer treatment centers in Canada and three centers in the United States were selected (biological safety cabinets, countertops, and floors in and adjacent to preparation areas; tabletops, chairs, and floors in administration areas). A solution of sodium hydroxide (0.03 M) was spread over the surface of each area. The surface was wiped with one or two absorbent tissues, which were then stored in plastic screw-top containers. Samples were stored at -40 degrees C before analysis of ifosfamide content (U.S. centers only) and cyclophosphamide content by gas chromatography in tandem with mass spectroscopy-mass spectroscopy and fluorouracil content by reverse-phase high-performance liquid chromatography with ultraviolet-light detection. Measurable amounts of the antineoplastic agents were detected in 75% of the pharmacy samples and 65% of the administration samples. In general, the levels of contamination were higher in the pharmacy areas than in the drug administration areas. The pharmacy area at the site with the highest number of drug preparations had considerably more drug contamination than the other sites. The results were similar for Canadian and U.S. centers. Substantial levels of contamination from three antineoplastic agents were detected on a variety of surfaces in pharmacy drug preparation areas and drug administration areas in six cancer treatment centers in Canada and the United States.

Antineoplastic Agents↗

Identification of three genes expressed primarily during development in Physarum polycephalum.

During the life cycle of Physarum polycephalum, uninucleate amoebae develop into multinucleate syncytial plasmodia. These two cell types differ greatly in cellular organisation, behaviour and gene expression. Classical genetic analysis has identified the mating-type gene, matA, as the key gene controlling the initiation of plasmodium development, but nothing is known about the molecular events controlled by matA. In order to identify genes involved in regulating plasmodium formation, we constructed a subtracted cDNA library from cells undergoing development. Three genes that have their highest levels of expression during plasmodium development were identified: redA, redB (regulated in development) and mynD (myosin). Both redA and redB are single-copy genes and are not members of gene families. Although redA has no significant sequence similarities to known genes, redB has sequence similarity to invertebrate sarcoplasmic calcium-binding proteins. The mynD gene is closely related to type II myosin heavy-chain genes from many organisms and is one of a family of type II myosin genes in P. polycephalum. Our results indicate that many more red genes remain to be identified, some of which may play key roles in controlling plasmodium formation.

Amino Acid Sequence↗

Prevention of epidural fibrosis with ADCON-L in presence of a durotomy during lumbar disc surgery: experiences with a pre-clinical model.

A potential complication of lumbo-sacral surgery is the inadvertent tear of the dura mater, which sometimes eludes intra-operative detection. ADCON-L, a bioabsorbable gel used in lumbosacral laminectomies or laminotomies, is a physical barrier to post-operative epidural fibrosis. Three experimental lumbar laminectomy studies were designed to assess in vivo the effects of ADCON-L when applied in presence of dural punctures in a rat model. In the first study, the durotomy was repaired with fibrin sealant, in the second experiment the dural defect was microsurgically sutured, while in a third protocol the durotomy was left unrepaired. In each study, dural healing was assessed respectively at 4, 8, or 12 weeks post-operatively. Blinded anatomical dissection and histopathology were used to compare results between treatments (sham operated control vs. ADCON-L). In the fibrin sealant experiment, an additional treatment group (fibrin sealant used together with ADCON-L) was included. The results of these studies consistently demonstrate that ADCON-L is an effective anti-fibrotic agent, and does not interfere with the normal dural healing processes following a meningeal puncture. The application of the gel may therefore be safe in presence of dural incisions, even when they are not identified during surgery, as demonstrated in these in vivo studies.

Animals↗

Direct HIV cytopathicity cannot account for CD4 decline in AIDS in the presence of homeostasis: a worst-case dynamic analysis.

The central paradox of HIV pathogenesis is that the viral burden, either free or cellular, seems too low to deplete the CD4 population by direct killing. Until recently, little data could be used to compare direct and indirect pathogenic theories critically. Clinical trials with potent new antiviral agents have measured important kinetic parameters of HIV infection, including viral and infected cell half-lives. This has led to the construction of explicit models of direct killing. Using a worst-case dynamic analysis, we show that such cytopathic models are untenable. Rates of infected cell removal are orders of magnitude too low to suppress steady state CD4 counts significantly in the face of lymphocyte replenishment, especially in early infection. Furthermore, the direct cytopathic models, as proposed, predict an extremely variable disease course across the broad range of observed viral burdens (five orders of magnitude), which is inconsistent with the relatively small differences in disease progression observed between patients. In contrast, immunologic theories of pathogenesis, such as homeostatic dysregulation based on immune activation, do not suffer from these difficulties and are more consistent with the natural history of HIV infection.

Acquired Immunodeficiency Syndrome↗

Anesthetic efficacy of the supplemental intraosseous injection for teeth with irreversible pulpitis.

The purpose of this study was to determine the efficacy of a supplemental intraosseous injection (IOI) of 2% lidocaine with 1:100,000 epinephrine using the Stabident device, after conventional anesthetic methods had failed. Patients who experienced pain during endodontic access and required a supplemental IOI using 0.45 to 0.90 ml of the local anesthetic were identified. All 37 of the patients treated had teeth diagnosed with irreversible pulpitis. Thirty-four of the teeth were mandibular posterior teeth, 2 were maxillary posterior teeth, and 1 was a maxillary anterior tooth. Patients with maxillary teeth had received infiltration anesthesia, and those with mandibular teeth had received an inferior alveolar nerve block in conjunction with long buccal infiltration. A minimum of 3.6 ml of local anesthetic was used with the conventional techniques. Modified visual analogue scales, coupled with operator evaluations, were used to measure success. The Stabident IOI was an effective supplemental anesthetic technique in 89% (+/- 5.1) or 33/37 patients evaluated. The 95% confidence interval was 74 to 97%. The IOI was successful in 91% (+/- 4.9) of the mandibular posterior teeth (31/34), and 67% of the maxillary teeth (2/3).

Adolescent↗

Estimation of spatiotemporal neural activity using radial basis function networks.

We report a method using radial basis function (RBF) networks to estimate the time evolution of population activity in topologically organized neural structures from single-neuron recordings. This is an important problem in neuroscience research, as such estimates may provide insights into systems-level function of these structures. Since single-unit neural data tends to be unevenly sampled and highly variable under similar behavioral conditions, obtaining such estimates is a difficult task. In particular, a class of cells in the superior colliculus called buildup neurons can have very narrow regions of saccade vectors for which they discharge at high rates but very large surround regions over which they discharge at low, but not zero, levels. Estimating the dynamic movement fields for these cells for two spatial dimensions at closely spaced timed intervals is a difficult problem, and no general method has been described that can be applied to all buildup cells. Estimation of individual collicular cells' spatiotemporal movement fields is a prerequisite for obtaining reliable two-dimensional estimates of the population activity on the collicular motor map during saccades. Therefore, we have developed several computational-geometry-based algorithms that regularize the data before computing a surface estimation using RBF networks. The method is then expanded to the problem of estimating simultaneous spatiotemporal activity occurring across the superior colliculus during a single movement (the inverse problem). In principle, this methodology could be applied to any neural structure with a regular, two-dimensional organization, provided a sufficient spatial distribution of sampled neurons is available.

Algorithms↗

The role of bound water in the stability of the triple-helical conformation of (Pro-Pro-Gly)10.

There is significant experimental evidence for bound water in collagen and related polymers. (Pro-Pro-Gly)10 [(PPG)10] is a polymer that forms a collagen-like triple-helical structure in aqueous solution. Like collagen, (PPG)10 adopts a structure in which side chains are mostly exposed to solvent, and the backbone polar groups are limited in their ability to form hydrogen bonds with each other. (PPG)10, like collagen, also has many of its backbone polar groups in positions that inhibit complete solvation in aqueous solution; thus the necessity of bound waters for stabilization of the structure. We have constructed a model for bound waters in (PPG)10, based on an examination of the geometry and steric environment of the backbone polar groups. As will become clear, the number of bound waters is determined by the geometry of the backbone carbonyl groups and the steric crowding surrounding them. In this model, each water forms one hydrogen bond with each of two backbone carbonyls from a glycine and a proline in different monomer chains, thus bridging the two carbonyls. The carbonyls in question are quite sterically crowded by neighboring (PPG)10 atoms and would not be likely to experience complete solvation by bulk solvent in aqueous solution. The bound waters are therefore likely to be present even in solution, since otherwise the unsatisfied hydrogen-bonding potential of the carbonyls would destabilize the structure. Other carbonyls also are sterically crowded and possibly prevented from experiencing full solvation, but are not in a favorable geometry for such bridging hydrogen bonds. The intra- and interchain interactions found in a previous computational study of (PPG)10 without bound waters are not disrupted by the addition of waters.

Models, Molecular↗

Two-dimensional saccade-related population activity in superior colliculus in monkey.

The two-dimensional distribution of population activity in the superior colliculus (SC) during saccadic eye movements in the monkey was estimated using radial basis functions. To make these ensemble activity estimates, cells in the deeper layers of the SC were recorded over much of the rostrocaudal (caudal to 3.8 mm from the rostral tip), mediolateral extent of this structure. The dynamic movement field of each cell was determined at 2-ms intervals around the time of saccades for a wide variety of horizontal and oblique movements. Collicular neurons were divided into partially overlapping dorsal and ventral cell layers on the basis of recorded depth in SC. The pattern of presaccadic activity was used as an additional discriminant to sort the cells in the two layers into separate burst (dorsal) and buildup (ventral) cell classes. Rostrocaudal and medioventral cell location on the colliculus was estimated from the optimal target vector for a cell's visual response rather than from the optimal motor vector. The former technique was more reliable for locating some buildup neurons because it produced locations that compared better with the locations suggested by electrical stimulation. From the movement field data and from the estimates of each cell's anatomic location, a similar algorithm was used to compute the two-dimensional population activity in the two layers of the SC during horizontal and oblique saccades. A subset of the sample of neurons, located near the horizontal meridian of the SC, first was used to compute one-dimensional dynamic population activity estimates for horizontal saccades to allow partial comparison to previous studies. Statistical analyses on the one-dimensional data were limited to saccades of </=20 degrees. The analyses indicated that while there was a small rostrally directed shift in the center of gravity of the distributed activity in the buildup cell layer, there was little support for the theory of a systematic rostrally directed spread of the leading edge of the activity. The two-dimensional results extend the previous one-dimensional estimates of collicular activity during saccades. Discharge in the burst layer was invariant in size for all saccade vectors and symmetrically arranged about a center of gravity that did not move during saccades. The size of the active area in the buildup layer grew modestly with saccade amplitude, whereas the distribution of activity was skewed toward the rostral end of the SC for saccades larger than 10 degrees. There was a small, but consistent shift in the center of gravity of the two-dimensional activity that was directed along the horizontal meridian (for horizontal movements) or an oblique meridian (for oblique movements) of the SC. However, the spread of activity during a saccade was as large or larger in the mediolateral direction as it was in the rostral direction. The results indicate that changes in activity occur in an extended zone on the SC, and in all directions but caudal, in the buildup layer during saccades and do not support the idea of a rostrally directed spread of activity as a dynamic control mechanism for saccades. Our results and those of previous investigators of collicular population activity may be limited by stationarity concerns in that the cells used to estimate population activity were recorded in several monkeys over an extended period of time to obtain a sufficient spatial sample.

Algorithms↗

A solid phase extraction method for determination of nicotine in serum and urine by isotope dilution gas chromatography/mass spectrometry with selected ion monitoring.

A rapid method for measuring nicotine concentration in serum and urine is described. Deuterated nicotine is used as an internal standard. Nicotine and deuterated nicotine are extracted using a copolymeric-bonded phase silica column. The extract is analysed by gas chromatography coupled with mass spectrometry (GC/MS) operating in selected ion monitoring mode. The method has a lower limit of detection of approximately 2 micrograms/L and is linear to at least 2000 micrograms/L. Within-run percentage coefficients of variation (% CV) are < 4 in both assays over a nicotine concentration range of 10-2000 micrograms/L. Between-run % CV in the serum assay are 5.4, 5.2, 4.8 and 5.9, respectively, at nicotine concentrations of 10, 15, 25, and 50 micrograms/L. Between-run % CV in the urine assay are 5.9, 4.5, 2.7 and 5.2, respectively, at nicotine concentrations of 100, 250, 500, and 2000 micrograms/L. The absolute recovery of nicotine is 61 +/- 6% (mean +/- SD) over the range of 10-250 micrograms/L. The assay has been used to measure serum nicotine concentrations and 24-h urinary excretion of nicotine to monitor the extent of replacement in subjects receiving transdermal nicotine therapy for smoking cessation.

Deuterium↗

G1-phase arrest is not a prerequisite for encystment in Physarum.

Amoebae of the Myxomycete Physarum polycephalum form resistant, walled cysts when the food bacteria in a culture have been consumed. No G1 phase has been detected in the vegetative amoebal cell cycle, most of which comprises the G2 phase. Mature cysts are also in G2, but it has been reported that a G1 phase of roughly 24 h, followed by an S phase, is obligatory prior to encystment. We used flow cytometry to determine the distribution of DNA contents in amoebal cultures at intervals during vegetative growth and encystment. In all cultures, the cells were predominantly in G2 phase, and the percentage of cells with G1 DNA content remained very low. We conclude that an extended G1 phase of 24 h did not occur in our cultures and cannot be a prerequisite for encystment.

Animals↗

Vehicle travel speeds and the incidence of fatal pedestrian crashes.

The aim of this study was to estimate the likely effect of reduced travel speeds on the incidence of pedestrian fatalities in Adelaide, Australia. The study was based on the results of detailed investigations of 176 fatal pedestrian crashes in the Adelaide area between 1983 and 1991. The method developed to estimate the effect of reduced travelling speed is described and supported by references to the published literature. A reduction in the speed limit from 60 to 50 km/h was one of four speed reduction scenarios considered. The smallest estimated reduction in fatal pedestrian collisions in the selection presented was 13%, for a scenario in which all drivers obeyed the existing speed limit. The largest estimated reduction was 48% for a scenario in which all drivers were travelling 10 km/h slower. The estimated reductions in fatalities obtained in this study are compared with those observed in places where the urban area speed limit has been lowered.

Acceleration↗

Cardiac surgery in the 21st century.

Cardiac surgery has developed over the past four decades in the United States as an important component of the entire health care industry. When analyzed as an industry, it is apparent that cardiac surgery is transitioning from its emerging or rapid growth phase to that of a mature industry. This transition, when combined with the global changes occurring in all of health care, has caused payers to reassess the value of cardiac surgical services and they have been targeted as overvalued and consuming a disproportionate share of health care resources. Several options are available to cardiac surgeons as to how they may potentially respond to the changes that are occurring in the external environment and reshaping the practice of the specialty. The active adaptation strategy appears to be the preferred choice but will require a substantial shift in the way cardiac surgery is practiced and reimbursed in the future.

Cardiac Surgical Procedures↗

The disintegration of superEBA cement in solutions with adjusted pH and osmolarity.

This study determined the disintegration of fast-set SuperEBA cement using ANSI/ADA Specification No. 30 (Spec #30) as well as modifications in pH, osmolarity, time before immersion, and duration of immersion that mimic the clinical, endodontic application of this material. After immersion intervals of 24 h, 1 wk, 1 m, 3 m, or 6 m, specimens were desiccated and weighed. The preimmersion and postdehydration weights were obtained to the nearest 1.0 mg and the percent weight loss from preimmersion levels was calculated. Adjusting the osmolarity to the physiologic level of 300 mOsm/kg resulted in significantly less weight loss (p < 0.05) than the control group in distilled water (no modification of Spec #30). The pH of the storage solution was found to be a significant factor in weight loss. As the acidity and the time of immersion increased, the weight loss also significantly increased with the greatest weight loss of 19.81% at pH 5.5 after 6 m storage. Immersion within 10 min of mixing was not significantly different (p > 0.05) in weight from the control of 1 h set-time. The 24 h weight loss measurements for the pHs of 5.5 and 6.4 were greater than the 1.5% allowed by Spec #30. All other 24 h measurements were less than the 1.5%.

Analysis of Variance↗

Comparison of various transport media on human periodontal ligament cell viability.

The purpose of this study was to determine the ability of various solutions to maintain human periodontal ligament cell (PDL) viability in vitro. PDL cells were obtained from extracted third molars and premolars of healthy individuals. These cells were placed into 24-well culture plates containing milk, Save-A-Tooth, Save-A-Tooth supplemented with platelet-derived growth factor-BB (PDGF), or Gatorade at a concentration of approximately 80,000/well. Cells left dry served as negative controls, and cells placed in Eagles' Minimal Essential Medium served as positive controls. At 1, 2, 4, 8, and 12 h, cell viability was evaluated using an MTS assay and an ELISA plate reader to determine optical density. ANOVA and Student-Newman-Keuls tests indicated that milk and Save-A-Tooth with PDGF are suitable as transport medium for avulsed teeth and that the addition of PDGF to Save-A-Tooth may enhance its ability to maintain PDL cell viability. They also suggests that Gatorade would be unsuitable as a transport medium.

Animals↗

A comparison of thermoplastic obturation techniques: adaptation to the canal walls.

The purpose of this study was to directly compare the ability of the three types of Thermafil obturators, the Obtura II thermoplasticized injectable technique, and the lateral condensation technique to obturate a standardized root canal. A split-tooth model was constructed and the root canal was obturated 20 times with each technique. The quality of each obturation was graded according to established criteria of adaptation. Statistical analysis of the results indicated that all the techniques were significantly different from each other (p < 0.0001) except for the plastic and titanium Thermafil groups (p > 0.05), which were similar. Based on the evaluated criteria, the Obtura II injectable technique demonstrated the best adaptation to the prepared root canal. This group was followed in order by the plastic and titanium Thermafil obturators, the stainless steel Thermafil obturators, and finally by the lateral condensation technique.

Analysis of Variance↗