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PubMed2005

The creation of 'consistent areas through time' (CATTs) in Scotland, 1981-2001.

Small area analysis of sociodemographic change over time is often impeded by the changing configuration of census zones for each decennial UK census. Approaches for matching zone configurations exist, but these typically require population estimation techniques, which inevitably involve some error. Because of the postcode-based geographical zoning system used in Scottish censuses, it is possible to create a local-area geography which is consistent for recent censuses. Here we present a methodology used to create three sets of consistent areas through time (CATTs) that can be used for analysing comparable small area data output from the 1981, 1991 and 2001 Censuses.

Demography↗
PubMed2004

Fibroblast adhesion to micro- and nano-heterogeneous topography using diblock copolymers and homopolymers.

Polymeric substrates of different surface chemistry and length scales were found to have profound influence on cell adhesion. The adhesion of fibroblasts on surfaces of oxidized polystyrene (PS), on surfaces modified with random copolymers of PS and poly(methyl methacrylate) [P(S-r-MMA)] with topographic features, and chemically patterned surfaces that varied in lateral length scales from nanometers to microns were studied. Surfaces with heterogeneous topographies were generated from thin film mixtures of a block copolymer, PS-b-MMA, with homopolymers of PS and PMMA. The two homopolymers macroscopically phase separated and, with the addition of diblock copolymer, the size scales of the phases decreased to nanometer dimensions. Cell spreading area analysis showed that a thin film of oxidized PS surface promoted adhesion whereas a thin film of P(S-r-MMA) surface did not. Fibroblast adhesion was examined on surfaces in which the lateral length scale varied from 60 nm to 6 microm. It was found that, as the lateral length scale between the oxidized PS surfaces decreased, cell spreading area and degree of actin stress fiber formation increased. In addition, scanning electron microscopy was used to evaluate the location of filopodia and lamellipodia. It was found that most of the filopodia and lamellipodia interacted with the oxidized PS surfaces. This can be attributed to both chemical and topographic surface interactions that prevent cells from interacting with the P(S-r-MMA) at the base of the topographic features.

Actins↗
PubMed2003

Global nutritional profiling for mutant and chemical mode-of-action analysis in filamentous fungi.

We describe a method for gene function discovery and chemical mode-of-action analysis via nutrient utilization using a high throughput Nutritional Profiling platform suitable for filamentous microorganisms. We have optimized the growth conditions for each fungal species to produce reproducible optical density growth measurements in microtiter plates. We validated the Nutritional Profiling platform using a nitrogen source utilization assay to analyze 21 Aspergillus nidulans strains with mutations in the master nitrogen regulatory gene, areA. Analysis of these data accurately reproduced expected results and provided new data to demonstrate that this platform is suitable for fine level phenotyping of filamentous fungi. Next, we analyzed the differential responses of two fungal species to a glutamine synthetase inhibitor, illustrating chemical mode-of-action analysis. Finally, a comparative phenotypic study was performed to characterize carbon catabolite repression in four fungal species using a carbon source utilization assay. The results demonstrate differentiation between two Aspergillus species and two diverse plant pathogens and provide a wealth of new data on fungal nutrient utilization. Thus, these assays can be used for gene function and chemical mode-of-action analysis at the whole organism level as well as interspecies comparisons in a variety of filamentous fungi. Additionally, because uniform distribution of growth within wells is maintained, comparisons between yeast and filamentous forms of a single organism can be performed.

Aminobutyrates↗
PubMed1992

Severe metallosis due to abnormal abrasion of the femoral head in a dual bearing hip prosthesis. A case report.

The authors report on a patient with a case of severe metallosis due to an abnormal abrasion of the femoral head. A primary arthroplasty was performed using a dual bearing hip prosthesis with acetabular bone grafting by ceramic screws. At the time of the revision surgery the synovia was black, and an analysis using a scanning electron microscope and scanning electron microscope-electron probe micro-analyzer revealed numerous small particles of small alumina ceramic on the inner surface of the bearing insert of high-density polyethylene. These particles, which came from the broken ceramic screws due to proximal migration of the prosthesis, scraped the femoral head away. A line and area analysis of the black synovia revealed that the synovia contained metal particles of a cobalt-chromium alloy as well as a cobalt ion. The patient's serum showed elevated concentrations of cobalt, chromium, and molybdenum that dramatically reduced 2 months after the revision surgery.

Adult↗
PubMed2006

The pattern and timing of diversification of Philippine endemic rodents: evidence from mitochondrial and nuclear gene sequences.

The 22 genera and 64 species of rodents (Muridae: Murinae) distributed in the Philippine Islands provide a unique opportunity to study patterns and processes of diversification in island systems. Over 90% of these rodent species are endemic to the archipelago, but the relative importance of dispersal from the mainland, dispersal within the archipelago, and in situ differentiation as explanations of this diversity remains unclear, as no phylogenetic hypothesis for these species and relevant mainland forms is currently available. Here we report the results of phylogenetic analyses of the endemic Philippine murines and a wide sampling of murine diversity from outside the archipelago, based on the mitochondrial cytochrome b gene and the nuclear-encoded IRBP exon 1. Analysis of our combined gene data set consistently identified five clades comprising endemic Philippine genera, suggesting multiple invasions of the archipelago. Molecular dating analyses using parametric and semiparametric methods suggest that colonization occurred in at least two stages, one ca. 15 Mya, and another 8 to 12 million years later, consistent with the previous recognition of "Old" and "New" endemic rodent faunas. Ancestral area analysis suggests that the Old Endemics invaded landmasses that are now part of the island of Luzon, whereas the three New Endemic clades may have colonized through either Mindanao, Luzon, or both. Further, our results suggest that most of the diversification of Philippine murines took place within the archipelago. Despite heterogeneity between nuclear and mitochondrial genes in most model parameters, combined analysis of the two data sets using both parsimony and likelihood increased phylogenetic resolution; however, the effect of data combination on support for resolved nodes was method dependent. In contrast, our results suggest that combination of mitochondrial and nuclear data to estimate relatively ancient divergence times can severely compromise those estimates, even when specific methods that account for rate heterogeneity among genes are employed. [Biogeography; divergence date estimation; mitochondrial DNA; molecular systematics; Murinae; nuclear exon; Philippines; phylogeny.].

Animals↗
PubMed2003

[Residual concentration of hexachlorocyclohexane in a contaminated site in Cidade dos Meninos, Duque de Caxias, Rio de Janeiro, Brazil, after calcium oxide treatment].

Hexachlorocyclohexanes (HCHs) are currently considered potentially carcinogenic to humans. In Brasil, severe soil contamination by HCHs has been identified at Cidade dos Meninos, Duque de Caxias, Rio de Janeiro, where an old HCH factory was abandoned 40 years ago, leaving 1,700 local residents at risk. Calcium oxide treatment was performed on the most heavily contaminated (focus) area. Analysis of superficial soil samples collected years after treatment still showed high residual HCH. Contamination levels as high as 6,200mg/Kg and 7,320mg/Kg were found for alpha- and beta-HCH isomers. For the gamma- and delta-HCH isomers, concentrations reached up to 140mg/Kg and 530mg/Kg, respectively. The results showed that calcium oxide treatment was not efficient to decontaminate the soil in this area.

Brazil↗
PubMed1998

Reciprocal dopamine-glutamate modulation of release in the basal ganglia.

Dopaminergic and glutamatergic transmissions have long been known to interact at multiple levels in the basal ganglia to modulate motor and cognitive functions. One important aspect of their interactions is represented by the reciprocal modulation of release. This topic has been the object of interest since the late 70's, particularly in the striatum and in midbrain dopaminergic areas (substantia nigra and ventral tegmental area). Analysis of glutamate-dopamine interactions in the control of each other's release is complicated by the fact that both glutamate and dopamine act on multiple receptor subtypes which can exert different effects. Therefore, glutamatergic modulation of dopamine release has been reviewed by analyzing the effects of glutamatergic selective receptor agonists and antagonists in the striatum (both motor and limbic portions) and in midbrain dopaminergic areas, as revealed by in vitro (slices, cell cultures, synaptosomes) and in vivo (push-pull, microdialysis and voltammetry techniques) experimental approaches. The same approach has been followed for dopaminergic modulation of glutamate release. The facilitatory nature of glutamate modulating both presynaptic and dendritic dopamine release has clearly emerged from in vitro studies. However, evidence is presented that, at least in the striatum and in the nucleus accumbens of awake rats, glutamate-mediated inhibitory effects may also occur. In vitro and in vivo experiments in the striatum and midbrain dopaminergic areas mainly depict dopamine as an inhibitory modulator of glutamate release. However, in vivo studies reporting dopamine D1 receptor mediated facilitatory effects are also considered. Therefore, the general notion that glutamate and dopamine act oppositely to regulate each other's release, is only partly supported by the available data. Conversely, the nature of the interaction between the two neurotransmitters seems to vary depending on the experimental approach, the brain area considered and the subtype of receptor involved.

Animals↗
PubMed2004

Electroencephalographic brain dynamics following manually responded visual targets.

Scalp-recorded electroencephalographic (EEG) signals produced by partial synchronization of cortical field activity mix locally synchronous electrical activities of many cortical areas. Analysis of event-related EEG signals typically assumes that poststimulus potentials emerge out of a flat baseline. Signals associated with a particular type of cognitive event are then assessed by averaging data from each scalp channel across trials, producing averaged event-related potentials (ERPs). ERP averaging, however, filters out much of the information about cortical dynamics available in the unaveraged data trials. Here, we studied the dynamics of cortical electrical activity while subjects detected and manually responded to visual targets, viewing signals retained in ERP averages not as responses of an otherwise silent system but as resulting from event-related alterations in ongoing EEG processes. We applied infomax independent component analysis to parse the dynamics of the unaveraged 31-channel EEG signals into maximally independent processes, then clustered the resulting processes across subjects by similarities in their scalp maps and activity power spectra, identifying nine classes of EEG processes with distinct spatial distributions and event-related dynamics. Coupled two-cycle postmotor theta bursts followed button presses in frontal midline and somatomotor clusters, while the broad postmotor "P300" positivity summed distinct contributions from several classes of frontal, parietal, and occipital processes. The observed event-related changes in local field activities, within and between cortical areas, may serve to modulate the strength of spike-based communication between cortical areas to update attention, expectancy, memory, and motor preparation during and after target recognition and speeded responding.

Adult↗
PubMed2004

The fractional excretion of soluble interleukin-2 receptor-alpha is an excellent predictor of the interleukin-2 receptor-alpha status after treatment with daclizumab.

BACKGROUND: Daclizumab is a humanized monoclonal antibody against the alpha-chain of the interleukin (IL)-2 receptor (R). The authors previously have shown that the urinary excretion of soluble (s) IL-2Ralpha is dependent on the presence of daclizumab in serum. The authors investigated whether the IL-2Ralpha status, as assessed by flow cytometric analysis, is reflected by the concentration of sIL-2Ralpha in the urine and serum. METHODS: Two hundred seventy-two measurements were performed in 46 renal transplant recipients who were treated with daclizumab in combination with tacrolimus and mycophenolate mofetil. Soluble IL-2Ralpha was measured in urine and serum with Immulite IL-2R, a solid-phase enzyme-linked immunosorbent assay. Complete blockade of the IL-2Ralpha was defined as the presence of less than 5% IL-2Ralpha+ lymphocytes in the CD3+ population. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of serum and urine sIL-2Ralpha in predicting IL-2Ralpha blockade. RESULTS: The calculated fractional excretion of sIL-2Ralpha proved to be an excellent predictor of the blockade of IL-2Ralpha (ROC analysis area under the curve, 0.95+/-0.01). A calculated fractional excretion of sIL-2Ralpha lower than 0.5% had a specificity of 100% and a sensitivity of 75% for the assessment of blockade of IL-2Ralpha. CONCLUSIONS: Blockade of IL-2Ralpha after treatment with daclizumab can reliably be assessed by calculation of the fractional excretion of sIL-2Ralpha. This method is easier to use compared with flow cytometric analysis of IL-2Ralpha+ lymphocytes.

Adult↗
PubMed2006

The geography of despair among 15-44-year-old men in England and Wales: putting suicide on the map.

OBJECTIVE: To investigate the spatial patterning and possible contributors to the geographical distribution of suicide among 15-44- year-old men. DESIGN: Small-area analysis and mapping of geo-coded 1988-94 suicide mortality data and 1991 census data using random-effects smoothing. SETTING: 9265 electoral wards in England and Wales (mean population of men aged 15-44- years: about 1220). MAIN RESULTS: Two main patterns emerged: (a) in all of the 10 most densely populated cities studied, suicide showed a "bull's-eye" pattern with rates highest in the inner-city areas and, in some cases, low rates in the peripheries, and (b) suicide rates were high in coastal areas, particularly those in more remote regions. Possible indicators of social fragmentation, such as the proportion of single-person households in an area, were most strongly and consistently associated with rates of suicide in both urban and rural areas. Levels of unemployment and long-term illness accounted for some of the coastal patterning. Although characteristics of areas accounted for more than half of the observed variability, substantial between-area variability in rates remained unexplained. CONCLUSIONS: The area characteristics investigated here did not fully account for the higher suicide rates observed in the most rural or remote areas. Alongside social and economic aspects, rural life itself may have an independent effect on the risk of suicide. A greater understanding of local geographies of suicide, and particularly the possible interactions between characteristics of people and their environments, might assist the design of prevention strategies that target those areas (and their characteristics) where risk is concentrated.

Adolescent↗
PubMed2003

Specificity of cerebellar vermian abnormalities in autism: a quantitative magnetic resonance imaging study.

To gain insight into the specificity of cerebellar vermian abnormalities reported in autism, we conducted a magnetic resonance imaging (MRI) study of boys with either of two conditions associated with autism, Down syndrome and fragile X syndrome, compared with boys with idiopathic autism and controls. The subjects, ranging in age from 3 to 9 years, included 16 boys with Down syndrome + autism and 11 boys with Down syndrome only; 13 boys with fragile X syndrome + autism and 9 boys with fragile X syndrome only; 10 boys with idiopathic autism; and 22 controls. Diagnosis of autism was based on DSM-IV criteria, confirmed primarily by the Autism Diagnostic Interview. T1-weighted midsagittal MRIs were used to measure midline structures. Intracranial area, reflecting brain size, was significantly smaller in subjects with Down syndrome. Therefore, all vermian measures were expressed as ratios to intracranial area. Analysis of covariance (covarying for age and IQ) demonstrated that posterior vermi (lobules VI-VII and VIII-X) were markedly smaller in both Down syndrome groups and those with fragile X syndrome only, whereas only lobules VI-VII were reduced in idiopathic autism. Factorial analyses of variance tested interactions between autism factor and the diagnosis of Down syndrome or fragile X syndrome. The size of lobules VI-VII/intracranial area was dependent on autism status only in fragile X syndrome, with ratios significantly larger in fragile X syndrome with autism with respect to fragile X syndrome only. We conclude that selective posterior vermis hypoplasia is seen not only in idiopathic autism but also in Down syndrome and some individuals with fragile X syndrome. However, reductions in vermian lobules VI and VII appear to be specific to idiopathic autism, whereas increased size of lobules VI and VII is associated with autism in fragile X syndrome. The latter results are consistent with MRI studies showing lobules VI-VII hyperplasia in a subset of subjects with idiopathic autism and cerebral and hippocampal enlargements in fragile X syndrome.

Autistic Disorder↗
PubMed2005

'Now nobody falls through the net': practitioners' perspectives on the Gold Standards Framework for community palliative care.

The Gold Standards Framework (GSF) seeks to facilitate consistent and high quality community palliative care through a set of guidelines, mechanisms and assessment tools. The present study set out to examine practitioners' perspectives on the GSF during its first national roll-out. Two general practices that had adopted the GSF were recruited in each of four geographical areas, and each matched as closely as possible with a non-GSF practice. Sixty-eight semi-structured telephone interviews were carried out with general practitioners and district nurses in 16 selected practices, along with the GSF facilitator and up to four other 'stakeholders' in each area. Analysis revealed that the majority of GSF participants felt that the framework had strengthened their provision of community palliative care. In particular, communication within primary health care teams and co-ordination of services improved, aspects which were better in the GSF practices than in the matched non-GSF practices. Practitioners felt there was more consistency of care, with a reduced likelihood that individual patients would 'slip through the net'. The most common areas of concern were in relation to the workload associated with the role of the GSF co-ordinator. Implications for the development and effective implementation of the framework and for further research are discussed.

Attitude of Health Personnel↗
PubMed2004

Comparison of selected analytical techniques for protein sizing, quantitation and molecular weight determination.

Protein analysis techniques are developing fast due to the growing number of proteins obtained by recombinant DNA techniques. In the present paper we compare selected techniques, which are used for protein sizing, quantitation and molecular weight determination: sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), lab-on-a-chip or microfluidics technology (LoaC), size exclusion chromatography (SEC) and mass spectrometry (MS). We compare advantages and limitations of each technique in respect to different application areas, analysis time, protein sizing and quantitation performance.

Chromatography↗
PubMed2006

Noninvasive assessment of repaired tetralogy of Fallot by magnetic resonance imaging and dynamic radionuclide studies.

BACKGROUND: This study was designed to validate the diagnostic accuracy of magnetic resonance imaging (MRI) in evaluating biventricular ejection fraction and to quantify pulmonary regurgitant fraction (PRF) in patients after repair of tetralogy of Fallot. METHODS: Two hundred and eighty survivors of repaired tetralogy of Fallot aged 42 months to 40 years (mean, 142.2 +/- 85.3 months) underwent cardiac MRI, first-pass and gated radionuclide ventriculography (RNV) for the assessment of biventricular function, and PRF after 89.26 +/- 42.40 months. The receiver operating characteristic curve analysis was done to quantify the diagnostic accuracy of MRI. RESULTS: There was statistically significant agreement between MRI and RNV in evaluating right and left ventricular function. An MRI-derived right ventricular ejection fraction 47.2% or greater than normal was associated with a sensitivity of 92.3% and a specificity of 92.3%. An MRI-derived left ventricular ejection fraction 53.9% or greater than normal was associated with a sensitivity of 93.2% and a specificity of 93.3%. Area analysis indicated that 97.34% (standard error [SE] = 0.0118) and 98.56% (SE = 0.0052) of the time values of right and left ventricular ejection fraction were higher for patients with normal right and left ventricular functions, respectively, compared with abnormal. There was a strong agreement between velocity-encoded and stroke volume-derived PRF [(r = 0.886, p < 0.001; d = 2.62 +/- 1.12, p < 0.0001; r' = 0.121, p = 0.051; b = 0.96 (SE = 0.012); p < 0.0001; ICC = 0.98, p < 0.0001). Higher PRF was associated with increased indexed right ventricular dimensions and inversely correlated with biventricular ejection fractions. CONCLUSIONS: The MRI-derived ejection fraction values predictably separate patients with normal ventricular function from abnormal. Velocity-encoded MRI can accurately quantitate PRF in tetralogy of Fallot.

Adolescent↗
PubMed2002

Defining the photochemical contribution to particulate matter in urban areas using time-series analysis.

The objective of this project is to demonstrate how the ambient air measurement record can be used to define the relationship between O3 (as a surrogate for photochemistry) and secondary particulate matter (PM) in urban air. The approach used is to develop a time-series transfer-function model describing the daily PM10 (PM with less than 10 microm aerodynamic diameter) concentration as a function of lagged PM and current and lagged O3, NO or NO2, CO, and SO2. Approximately 3 years of daily average PM10, daily maximum 8-hr average O3 and CO, daily 24-hr average SO2 and NO2, and daily 6:00 a.m.-9:00 a.m. average NO from the Aerometric Information Retrieval System (AIRS) air quality subsystem are used for this analysis. Urban areas modeled are Chicago, IL; Los Angeles, CA; Phoenix, AZ; Philadelphia, PA; Sacramento, CA; and Detroit, MI. Time-series analysis identified significant autocorrelation in the O3, PM10, NO, NO2, CO, and SO2 series. Cross correlations between PM10 (dependent variable) and gaseous pollutants (independent variables) show that all of the gases are significantly correlated with PM10 and that O3 is also significantly correlated lagged up to two previous days. Once a transfer-function model of current PM10 is defined for an urban location, the effect of an O3-control strategy on PM concentrations is estimated by calculating daily PM10 concentrations with reduced O3 concentrations. Forecasted summertime PM10 reductions resulting from a 5 percent decrease in ambient O3 range from 1.2 microg/m3 (3.03%) in Chicago to 3.9 microg/m3 (7.65%) in Phoenix.

Air Pollutants↗
PubMed1986

Unilateral lesions in locus coeruleus area enhance paradoxical sleep.

To clarify the effect of locus coeruleus (LC) lesions in sleep mechanisms, modifications in the amount of wakefulness (W), drowsiness (D), slow sleep (SS) and paradoxical sleep (PS) were examined in 9 cats with unilateral lesions in the dorso-lateral pontine tegmentum and in 3 sham-operated controls. In 4 animals the LC area was unilaterally destroyed--affecting structures that have previously been proposed as PGO-off elements--while the remaining 5 cats had lesions situated close to but sparing the LC area. Analysis of variance among baseline values of all cats, 'postlesion' values of the sham-operated controls and the postlesion values of the 2 groups of operated animals, indicated that the variations of W, D and SS among the different groups were not statistically significant. Only variations in the time spent in PS reached statistically significant values. Individual comparisons between PS values of the 4 groups showed that only an increase of PS in the animals with lesions in the LC area was statistically significant, in comparison with the PS values of the remaining groups. These results indicate that the dorso-lateral pontine area, which is considered to exert a tonic inhibitory influence in the generation of the phasic activity during PS, also mediates in the sleep-wakefulness cycle as an inhibitory region for controlling proportions of PS.

Animals↗
PubMed1992

Relative potency estimates of acceptable residues and reentry intervals after nerve agent release.

In the event of an unplanned release of a chemical warfare agent during any stage of the Chemical Stockpile Disposal Program, the potential exists for off-post contamination of drinking water, forage crops, grains, garden produce, and livestock. The more persistent agents, such as the organophosphate nerve agent VX, pose the greatest human health concern for reentry. A relative potency approach comparing the toxicity of VX to organophosphate insecticide analogues is developed and used to estimate allowable residues for VX in agricultural products and reentry intervals for public access to contaminated areas. Analysis of mammalian LD50 data by all exposure routes indicates that VX is 10(3) to 10(4) times more toxic than most commercially available organophosphate insecticides. Thus, allowable residues of VX could be considered at concentration levels 10(3) to 10(4) lower than those established for certain insecticides by the U.S. EPA. Evaluation of reentry intervals developed for these organophosphate analogues indicate that, if environmental monitoring cannot reliably demonstrate acceptable levels of VX, restricted access to suspect or contaminated areas may be on the order of weeks to months following agent release. Planning for relocation, mass care centers, and quarantine should take this time period into account.

Chemical Warfare Agents↗
PubMed2004

Residential proximity to high-voltage power lines and risk of childhood hematological malignancies.

BACKGROUND: Epidemiologic studies of electromagnetic fields and childhood cancers have focused on home exposure. The authors investigated whether residence in districts near high-voltage power lines is associated with childhood hematological malignancies, using small area analysis. METHODS: Among 50,000 children in a city in Japan, 14 cases aged younger than 15 years were diagnosed with these malignancies in the period from 1992 through 2001. A total of 294 districts constituting this city were classified according to their proximity to high-voltage power lines (either 66 kV or 220 kV). Mantel-Haenszel rate ratio is used to calculate incidence rate ratio and its 95% confidence interval (CI). RESULTS: Compared to districts of which no area fell within 300 m of high-voltage power lines, districts in which at least 50% of the area fell within 300 m of high-voltage power lines demonstrated an increased risk (incidence rate ratio: 2.2; 95% CI: 0.5-9.0). The association was strengthened for homes in which patients had resided for the longest interval of their lives (incidence rate ratio: 3.4; 95% CI: 0.9-13.2). Point-in-time measurements showed no increase in magnetic field levels for patient homes in districts near the lines. CONCLUSION: An increased, albeit nonsignificant, risk of childhood hematological malignancies associated with residential proximity to high-voltage power lines warrants further investigations.

Adolescent↗