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Signal-averaged isoharmonic body surface maps of patients with ischemic cardiomyopathy.

INTRODUCTION: Prevention of sudden arrhythmic cardiac death depends on accurate identification of individuals at high risk. Previous studies of signals recorded directly from arrhythmogenic tissue suggested that the predictive value of the signal-averaged ECG could be enhanced by expanded temporal, spectral, and spatial analysis. Accordingly, we performed a prospective study of 192-lead signal-averaged body surface maps from 43 patients with ischemic cardiomyopathy referred for electrophysiologic study. Three groups were included: 15 patients with clinical ventricular tachycardia (VT), 12 patients with inducible VT, and 16 patients with non-VT. METHODS AND RESULTS: The patients were well matched with regard to age, gender, infarct location, ejection fraction (28% +/- 9%), QRS duration, and incidence of nonsustained VT (96%). Isoharmonic maps of the entire cardiac cycle were constructed for each patient. The peaks of the 1-7 Hz isoharmonic maps distinguished patients with clinical VT from non-VT and inducible VT patients (1,152 +/- 273, 852 +/- 283, and 808 +/- 272, respectively; P = 0.003). After prospective observation for 22 +/- 16 months, the combined endpoint of spontaneous sustained VT, ventricular fibrillation, appropriate defibrillator therapy, and death was predicted by inducibility of VT (relative risk 3.8, P = 0.008) and by the signal-averaged isoharmonic body surface map (relative risk 3.1, P = 0.02). CONCLUSION: These results confirm the diagnostic utility of signal-averaged isoharmonic body surface maps in a rigorously defined patient population.

Aged↗

Differential and spatial aspects of suicide mortality in New South Wales and Sydney, 1980 to 1991.

Occupational and marital status dimensions of suicide mortality in New South Wales were examined for the periods 1980 to 1985 and 1986 to 1989-90 respectively, and marital status and birthplace group mortality profiles were examined in relation to grouped occupations, with a view to identifying the relative influence of these differentiating factors on suicide mortality. Spatial analysis was undertaken for different ages, in major regions of New South Wales and statistical local areas in Sydney for the period 1985 to 1991, and associations with socioeconomic characteristics of geographic areas were investigated. Despite residential revitalisation in inner city areas, higher mortality in several inner city localities has persisted over time while levels have risen in some outer areas. Never-married and divorced men in manual work were most at risk of committing suicide and never-married and divorced women had elevated suicide levels. Male suicide levels were elevated among farmers and related workers, and youth and adult male suicide levels were elevated in inland regions of the state. Possible explanations for the variations are discussed.

Adult↗

A Monte Carlo multiple source model applied to radiosurgery narrow photon beams.

Monte Carlo (MC) methods are nowadays often used in the field of radiotherapy. Through successive steps, radiation fields are simulated, producing source Phase Space Data (PSD) that enable a dose calculation with good accuracy. Narrow photon beams used in radiosurgery can also be simulated by MC codes. However, the poor efficiency in simulating these narrow photon beams produces PSD whose quality prevents calculating dose with the required accuracy. To overcome this difficulty, a multiple source model was developed that enhances the quality of the reconstructed PSD, reducing also the time and storage capacities. This multiple source model was based on the full MC simulation, performed with the MC code MCNP4C, of the Siemens Mevatron KD2 (6 MV mode) linear accelerator head and additional collimators. The full simulation allowed the characterization of the particles coming from the accelerator head and from the additional collimators that shape the narrow photon beams used in radiosurgery treatments. Eight relevant photon virtual sources were identified from the full characterization analysis. Spatial and energy distributions were stored in histograms for the virtual sources representing the accelerator head components and the additional collimators. The photon directions were calculated for virtual sources representing the accelerator head components whereas, for the virtual sources representing the additional collimators, they were recorded into histograms. All these histograms were included in the MC code, DPM code and using a sampling procedure that reconstructed the PSDs, dose distributions were calculated in a water phantom divided in 20000 voxels of 1 x 1 x 5 mm3. The model accurately calculates dose distributions in the water phantom for all the additional collimators; for depth dose curves, associated errors at 2sigma were lower than 2.5% until a depth of 202.5 mm for all the additional collimators and for profiles at various depths, deviations between measured and calculated values were less than 2.5% or 1 mm.

Algorithms↗

Synthetic array measurements of acoustical waves propagating into a water-saturated sandy bottom for a smoothed and a roughened interface

Measurements of acoustical waves propagating in an unconsolidated water-saturated porous medium that involved the use of a two-dimensional synthetic array technique are presented. From these measurements, wave-front propagation is evaluated using time domain, wave-number frequency and two-dimensional spatial analysis techniques. First, a synthetic array measurement is employed to study sound penetration for a "smoothed" interface condition. This smoothed interface measurement is then compared to an identical synthetic array measurement with a "roughened" interface. A comparison of the smoothed and roughened interface measurements shows enhanced bottom penetration at shallow grazing angles as a result of the roughened interface. At shallow grazing angles, this scattered pressure from the roughened interface has the appearance of a wave front in the water-saturated porous medium that has a virtual wave speed of approximately 1200 m/s. Slower compressional waves in the sandy bottom are not observed.

Journal Article↗

Stimulation of cells using EGF-coated magnetic beads.

The ability to determine the spatial localization of signals can assist in defining the regulation of specific signaling pathways within the cell. Localized application of a stimulus, followed by imaging of various proteins or their phosphorylated products, allows visualization of the propagation scales of responses to the stimulus. To obtain a localized stimulus of epidermal growth factor (EGF), we bound the ligand to magnetic beads, which could be rapidly pulled onto cell surfaces by a magnet. This method allows the spatial analysis of EGF-induced signaling pathways.

Adenocarcinoma↗

Multicellular organization in a degradative biofilm community.

Diclofop methyl, a commercial herbicide, was used as the sole carbon source to cultivate diclofop-degrading biofilms in continuous-flow slide culture. The biofilms were analyzed by using scanning confocal laser microscopy and image analysis. Spatial relationships among members of the community were distinctive to diclofop-grown biofilms. These relationships did not develop when the biofilms were grown on more labile substrates but were conserved when the biofilms were cultivated with other chlorinated ring compounds. The structures included conical bacterial consortia rising to 30 mum above the surrounding biofilm, grape-like clusters of cocci embedded in a matrix of perpendicularly oriented bacilli, and other highly specific patterns of intra- and intergeneric cellular coaggregation and growth. These unique consortial relationships indicated that syntrophic interactions may be necessary for optimal degradation of diclofop methyl and other chlorinated ring compounds.

Journal Article↗

Quorum-sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns.

Acylated homoserine lactone molecules are used by a number of gram-negative bacteria to regulate cell density-dependent gene expression by a mechanism known as quorum sensing (QS). In Pseudomonas aeruginosa, QS or cell-to-cell signaling controls expression of a number of virulence factors, as well as biofilm differentiation. In this study, we investigated the role played by the las and rhl QS systems during the early stages of static biofilm formation when cells are adhering to a surface and forming microcolonies. These studies revealed a marked difference in biofilm formation between the PAO1 parent and the QS mutants when glucose, but not citrate, was used as the sole carbon source. To further elucidate the contribution of lasI and rhlI to biofilm maturation, we utilized fusions to unstable green fluorescent protein in concert with confocal microscopy to perform real-time temporal and spatial studies of these genes in a flowing environment. During the course of 8-day biofilm development, lasI expression was found to progressively decrease over time. Conversely, rhlI expression remained steady throughout biofilm development but occurred in a lower percentage of cells. Spatial analysis revealed that lasI and rhlI were maximally expressed in cells located at the substratum and that expression decreased with increasing biofilm height. Because QS was shown previously to be involved in biofilm differentiation, these findings have important implications for the design of biofilm prevention and eradication strategies.

Bacterial Proteins↗

Risk adjustment for hospital use using social security data: cross sectional small area analysis.

OBJECTIVES: To identify demographic and socioeconomic determinants of need for acute hospital treatment at small area level. To establish whether there is a relation between poverty and use of inpatient services. To devise a risk adjustment formula for distributing public funds for hospital services using, as far as possible, variables that can be updated between censuses. DESIGN: Cross sectional analysis. Spatial interactive modelling was used to quantify the proximity of the population to health service facilities. Two stage weighted least squares regression was used to model use against supply of hospital and community services and a wide range of potential needs drivers including health, socioeconomic census variables, uptake of income support and family credit, and religious denomination. SETTING: Northern Ireland. MAIN OUTCOME MEASURE: Intensity of use of inpatient services. RESULTS: After endogeneity of supply and use was taken into account, a statistical model was produced that predicted use based on five variables: income support, family credit, elderly people living alone, all ages standardised mortality ratio, and low birth weight. The main effect of the formula produced is to move resources from urban to rural areas. CONCLUSIONS: This work has produced a population risk adjustment formula for acute hospital treatment in which four of the five variables can be updated annually rather than relying on census derived data. Inclusion of the social security data makes a substantial difference to the model and to the results produced by the formula.

Adult↗

Impact of leukocytes and platelets in mediating hepatocyte apoptosis in a rat model of systemic endotoxemia.

Apoptotic hepatocytes have been demonstrated to represent an important signal for transmigration of leukocytes sequestered in sinusoids during endotoxemia in vivo. Beside leukocytes, platelets and their adhesion to endothelial cells and leukocytes have been implicated in inflammatory liver injury. Using in vivo multifluorescence microscopy, we examined the possibility that hepatocellular apoptosis causes both leukocytes and platelets to colocalize within the sinusoidal microvasculature of endotoxemic livers. We further addressed the issue whether cellular colocalization with apoptotic hepatocytes is cause or consequence of apoptosis. Intraperitoneal exposure of rats with LPS (5 mg/kg) induced liver injury after 6 and 16 h, as given by nutritive perfusion failure (20 +/- 2 and 21 +/- 2%), intrahepatic leukocyte (60 +/- 10 and 121 +/- 48 cells/mm(2)), and platelet (12 +/- 4 and 34 +/- 4 cells/mm(2)) accumulation as well as parenchymal cell apoptosis (4 +/- 1 and 11 +/- 2 cells/mm(2)) and caspase cleavage (4.7 +/- 2.4- and 7.0 +/- 3.0-fold increase; P < 0.05 vs. saline-exposed controls). Higher doses of LPS (10 mg/kg ip) further increased intrahepatic leukocyte and platelet accumulation but not the extent of parenchymal apoptosis. Detailed spatial analysis revealed colocalization of leukocytes (range 12-24%) but barely of platelets (<6%) with apoptotic hepatocytes in all endotoxemic groups studied. It is of interest, however, that platelets were found at increasing rates in colocalization with leukocytes at 6 and 16 h after LPS exposure (5 mg/kg LPS: 7 +/- 3 and 25 +/- 6%; 10 mg/kg LPS: 11 +/- 4 and 14 +/- 1%). Platelet-leukocyte events significantly correlated with the extent of caspase cleavage as an indicator of tissue apoptosis (P < 0.05; r = 0.82). Blockade of apoptosis by a pan-caspase inhibitor caused a significant reduction of leukocyte adherence and platelet-leukocyte colocalization on LPS exposure. On the other hand, leukocytopenic animals revealed reduced hepatocyte apoptosis, although values still exceeded those of controls, and in leuko- and thrombocytopenic animals, hepatocyte apoptosis was found reduced to control values. Taken together, LPS-associated hepatocyte apoptosis seems to be initiated by circulating blood cells that become adherent within the liver but might also contribute to further sustain the inflammatory cell-cell response.

Amino Acid Chloromethyl Ketones↗

Oxygen consumption in the avascular guinea pig retina.

Oxygen consumption across the retina of a mammal with a naturally avascular retina has not previously been investigated. The oxygen consumption across the avascular retina of the guinea pig was measured in vivo by spatial analysis of the intraretinal oxygen profile. The avascular nature of the guinea pig retina allows the inner retina to be included in the analysis without disrupting the normal physiological state of the retina. Oxygen-sensitive microelectrodes (1-micron tip) were used to make high-resolution measurements of oxygen tension through the retina of anesthetized, mechanically ventilated guinea pigs (n = 10). Oxygen profiles were then analyzed in terms of oxygen tension as a function of distance from the choriocapillaris/Bruch's membrane, and the data were fitted to an established mathematical model of retinal oxygen consumption. The average oxygen consumption of the full thickness of the guinea pig retina was 1.1 +/- 0.09 ml O2.min-1 x 100 g-1 (n = 10). The average oxygen consumption of the outer half of the retina was 2.07 +/- 0.17 ml O2.min-1 x 100 g-1, while that of the inner half was only 0.12 +/- 0.04 ml O2.min-1 x 100 g-1. A localized region of high oxygen consumption was identified in the outer retina in every case, and this region accounted for an average of 93.9 +/- 2.0% of the total retinal oxygen consumption. Only 5.2 +/- 1.4% of the total oxygen consumption was attributable to the inner half of the retina. When choroidal oxygen tension was increased via a combination of systemic hyperoxia and hypercapnia, high oxygen levels could be sustained in all retinal layers. Under these conditions of an excess oxygen supply, the inner retina still consumed only 0.45 +/- 0.11 ml O2.min-1 x 100 g-1, which was 13.8 +/- 2.5% of the total retinal oxygen consumed. The relatively low oxygen consumption in the inner retina of the guinea pig may reflect an interesting adaptation to the constraints imposed by the absence of a retinal circulation in this species.

Animals↗

Measurement of intracellular calcium.

To a certain extent, all cellular, physiological, and pathological phenomena that occur in cells are accompanied by ionic changes. The development of techniques allowing the measurement of such ion activities has contributed substantially to our understanding of normal and abnormal cellular function. Digital video microscopy, confocal laser scanning microscopy, and more recently multiphoton microscopy have allowed the precise spatial analysis of intracellular ion activity at the subcellular level in addition to measurement of its concentration. It is well known that Ca2+ regulates numerous physiological cellular phenomena as a second messenger as well as triggering pathological events such as cell injury and death. A number of methods have been developed to measure intracellular Ca2+. In this review, we summarize the advantages and pitfalls of a variety of Ca2+ indicators used in both optical and nonoptical techniques employed for measuring intracellular Ca2+ concentration.

Animals↗

[Mortality of gastric cancer in Catalonia, Spain: geographical distribution and time trends from 1986 to 2000].

BACKGROUND AND OBJECTIVE: The aims of this study are to describe the time trends and the changes in the spatial distribution of stomach cancer mortality by gender, in Catalonia, Spain, in the period 1986-2000. MATERIAL AND METHOD: The mortality data comes from the Mortality Register for Catalonia at the Health Department and the population data from the Institute of Statistics for Catalonia. To analyze time trends, a Poisson regression model was adjusted for each gender. To analyze the geographical distribution, a Bayesian hierarchical model was used. RESULTS: During the period 1986-2000 the number of deaths from stomach cancer was 8,627 for males and 5,831 for females. During this period the estimated decrease in mortality was 3.13% for males and 3.91% for females. The spatial analysis showed the lowest mortality risk areas along the coast while the mortality risk increased toward the zones in the interior. This geographical pattern is very similar for both sexes but in the lasts years of the period it has been fading. CONCLUSIONS: The time trends and the geographical pattern of stomach cancer mortality in Catalonia is similar for both sexes and it is consistent with the trends observed in other developed countries. This suggests a relationship with improved food habits and a better accessibility to health care in the areas of higher risk.

Catchment Area, Health↗

Quantitative assessment of myocardial ischemia and necrosis by continuous vectorcardiography and measurement of creatine kinase release in patients.

The accuracy of the use of the maximal QRS vector difference to estimate myocardial infarct size irrespective of infarct location was compared with that of measurement of cumulative creatine kinase (CK) release. Sixty patients with acute myocardial infarction and a history of symptoms of less than 4 hr duration were followed for 24 to 72 hr with orthogonal vectorcardiography and CK release analysis. Spatial QRS vector differences were calculated between the first QRS complex recorded and subsequent QRS complexes at timed intervals. The QRS vector difference increased rapidly and reached a plateau at an average 12.1 hr after onset of symptoms, as compared with 34.0 hr for the cumulated CK release. In 42% of the patients a stepwise progression of infarct evolution was observed. Irrespective of infarct location the maximal spatial ST vector magnitude was related to the ultimate QRS vector difference (r = .80) and to the cumulative amount of CK released (r = .64). Furthermore, maximal QRS vector difference correlated well with the maximal cumulative CK release (r = .64) Ten patients had possible infarct expansion, as indicated by recurrent QRS changes without concomitant CK release. Fifteen patients had infarct extension that was indicated by secondary CK release and that in seven patients was associated with further QRS changes. Infarct extension caused an approximate 25% increase in infarct size. Spatial ST vector magnitude, QRS vector difference, and cumulative CK release are complementary measures in the quantification of evolving myocardial injury after acute coronary occlusion and in the determination of sequels to therapeutic interventions.

Adult↗

Immunofluorescence and confocal laser scanning microscopy of chronic myeloproliferative disorders on archival formaldehyde-fixed bone marrow.

Spatial analysis of the histoarchitecture and photographic documentation at high resolution are the principal advantages of confocal laser scanning microscopy (CLSM) over conventional fluorescence microscopy (CFM) if combined with appropriate software. Restrictions for the use of CFM and CLSM, on the other hand, include nonspecific background fluorescence, fading of photolabile fluorochromes, and both tissue-specific and fixation-induced autofluorescence. Most of those shortcomings can now be avoided. Autofluorescence, the most limiting factor of high-resolution CLSM, was recently controlled also for paraffin sections of archival formaldehyde-fixed tissues. This allowed the present study on cytoskeletal fibers and extracellular matrix proteins in both neoplastic cells of myeloproliferative disorders and in medullary stromal cells using CLSM under proper autofluorescence control. By multiple fluorescence labeling, we found that the intracellular smooth muscle alpha-actin (SMA) fibers and the two extracellular adhesive matrix proteins tenascin and fibronectin vary in their presence in stromal and/or myeloid cells according to the degree of bone marrow fibrosis in chronic myeloproliferative disorders (CMPDs). CLSM offers further insight in our attempts to understand a complex interplay between the two cellular compartments.

Bone Marrow↗

Siting MSW landfills on Lesvos island with a GIS-based methodology.

The siting of Municipal Solid Waste (MSW) landfills in Greece is a difficult process due to land resource limitations, the country's mountainous, insular and primarily water permeable terrain as well as an exacerbated public opposition (NIMBY syndrome). A GIS-based methodology is presented here with the goal to identify and rank the candidate landfill sites for the entire island of Lesvos. The initial step of the methodology comprises a GIS-based spatial analysis that uses 10 criteria, by excluding all areas unsuitable for any waste disposal activity. The pre-selected areas are then further assessed by fieldwork and candidate landfill sites are determined. The candidate sites are ranked using 19 criteria with predefined weight coefficients on a 0 to 10 grading scale. The weight coefficients are estimated for each criterion using the Analytic Hierarchy Process (AHP), while the grading scheme is based on pre-defined guidelines. An overall suitability index is produced for each candidate site allowing comparison and best case selection. A case study for the island of Lesvos is presented here, in which eight candidate landfill sites were finally selected and ranked. Social factors highly determined the ultimate selection of the site in Lesvos, since the third rather than the first site suggested by the methodology, was finally approved by local authorities.

Decision Making↗

Evaluation of school absenteeism data for early outbreak detection, New York City.

BACKGROUND: School absenteeism data may have utility as an early indicator of disease outbreaks, however their value should be critically examined. This paper describes an evaluation of the utility of school absenteeism data for early outbreak detection in New York City (NYC). METHODS: To assess citywide temporal trends in absenteeism, we downloaded three years (2001-02, 2002-03, 2003-04) of daily school attendance data from the NYC Department of Education (DOE) website. We applied the CuSum method to identify aberrations in the adjusted daily percent absent. A spatial scan statistic was used to assess geographic clustering in absenteeism for the 2001-02 academic year. RESULTS: Moderate increases in absenteeism were observed among children during peak influenza season. Spatial analysis detected 790 significant clusters of absenteeism among elementary school children (p < 0.01), two of which occurred during a previously reported outbreak. CONCLUSION: Monitoring school absenteeism may be moderately useful for detecting large citywide epidemics, however, school-level data were noisy and we were unable to demonstrate any practical value in using cluster analysis to detect localized outbreaks. Based on these results, we will not implement prospective monitoring of school absenteeism data, but are evaluating the utility of more specific school-based data for outbreak detection.

Absenteeism↗

Acute symptoms related to air pollution in urban areas: a study protocol.

BACKGROUND: The harmful effects of urban air pollution on general population in terms of annoying symptoms are not adequately evaluated. This is in contrast to the hospital admissions and short term mortality. The present study protocol is designed to assess the association between the level of exposure to certain ambient air pollutants and a wide range of relevant symptoms. Awareness of the impact of pollution on the population at large will make our estimates of the pertinent covert burden imposed on the society more accurate. METHODS/DESIGN: A cross sectional study with spatial analysis for the addresses of the participants was conducted. Data were collected via telephone interviews administered to a representative sample of civilians over age four in the city. Households were selected using random digit dialling procedures and randomization within each household was also performed to select the person to be interviewed. Levels of exposure are quantified by extrapolating the addresses of the study population over the air pollution matrix of the city at the time of the interview and also for different lag times. This information system uses the data from multiple air pollution monitoring stations in conjunction with meteorological data. General linear models are applied for statistical analysis. DISCUSSION: The important limitations of cross-sectional studies on acute effects of air pollution are personal confounders and measurement error for exposure. A wide range of confounders in this study are controlled for in the statistical analysis. Exposure error may be minimised by employing a validated geographical information system that provides accurate estimates and getting detailed information on locations of individual participants during the day. The widespread operation of open air conditioning systems in the target urban area which brings about excellent mixing of the outdoor and indoor air increases the validity of outdoor pollutants levels that are taken as exposure levels.

Air Pollution↗

Use of satellite imagery in constructing a household GIS database for health studies in Karachi, Pakistan.

BACKGROUND: Household-level geographic information systems (GIS) database are usually constructed using the geographic positioning system (GPS). In some research settings, GPS receivers may fail to capture accurate readings due to structural barriers such as tall buildings. We faced this problem when constructing a household GIS database for research sites in Karachi, Pakistan because the sites are comprised of congested groups of multi-storied building and narrow lanes. In order to overcome this problem, we used high resolution satellite imagery (IKONOS) to extract relevant geographic information. RESULTS: The use of IKONOS satellite imagery allowed us to construct an accurate household GIS database, which included the size and orientation of the houses. The GIS database was then merged with health data, and spatial analysis of health was possible. CONCLUSIONS: The methodological issues introduced in this paper provide solutions to the technical barriers in constructing household GIS database in a heavily populated urban setting.

Journal Article↗