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PubMed1989

Small area mortality patterns.

Little information on the health of populations living in small geographic areas of Ireland is available and it is therefore difficult to clearly identify small communities whose health is significantly below average. The aim of this study was to identify areas within Dublin having above average death rates by application of the technique of small area analysis. By using mortality and census data and by calculating standardised mortality ratios, a number of electoral wards/district electoral divisions in Dublin with significantly elevated mortality rates from all causes and from specific disease groups were identified. In general these were in inner city areas and new suburbs to the north and west of the city. A considerable proportion of the excess mortality can be attributed to conditions amenable to preventive measures. Before specific intervention is attempted, local investigation by Directors of Community Care/Medical Officers of Health will be necessary in order to confirm the findings and to identify factors which may be amenable to prevention. If intervention is attempted it should be carefully planned and should be implemented on a pilot basis initially.

Demography↗
PubMed2005

Audiometric threshold shift definitions: simulations and suggestions.

OBJECTIVES: Determine (1) whether pure-tone average (PTA) or "any frequency" (AF) definitions of significant threshold shift (STS) are more accurate under different conditions; (2) whether STS definitions applied twice are more accurate than when applied once; (3) whether three surrogate analysis methods applicable to real-world audiometric data can appropriately measure the accuracy of STS definitions; and (4) whether evidence from previous studies supports a change in the current STS definition used by the Occupational Safety and Health Administration (OSHA); (5) make recommendations for future research. DESIGN: Computer simulation of periodic audiograms, with typical test-retest variability, from seven groups of individuals (N = 1000 each), with or without threshold shifts of different sizes at different frequencies; receiver operating characteristic area analysis to determine relative accuracy of PTA and AF decision variables, applied once or twice; testing of surrogate methods (confirmation, variability, and comparison) against receiver operating characteristic areas in estimation of accuracy of decision variables; review of previous studies, considering the limitations of the surrogate methods that were used. RESULTS: Either AF or PTA definitions may be preferable, depending on whether the genuine threshold shift has occurred at a single frequency or across a range of frequencies. Including too few or too many frequencies degrades the performance of both AF and PTA variables. An STS decision variable performs only slightly better when applied twice than when applied once. The surrogate methods can be useful, but all have important caveats: The comparison method is best, but only when an appropriate control group is available; the variability method is intermediate but requires that each decision variable be tested at multiple criterion values for reliable results. The confirmation method, which was the least accurate in assessing true performance, also requires testing at multiple levels. Even when this is done, it markedly exaggerates the benefit of applying an STS definition twice and makes STS definitions that identify large numbers of individuals falsely appear to be more accurate than definitions that identify smaller numbers of individuals. Taking these caveats into account, previous studies do not offer convincing evidence for a change in the current OSHA STS definition. CONCLUSIONS: Choice of an STS definition requires three judgments that cannot be made based on the type of analysis discussed in this report: The range of frequencies to be tested, whether to require that an STS definition be applied twice, and the acceptable magnitude of false-positive error. Once these judgments have been made, the techniques discussed here can assist in selecting the appropriate decision variable (typically PTA or AF) and a criterion value that yields an acceptable false-positive rate. Additional research using the techniques described in this report with either new or old audiometric databases could help determine whether any STS definition is significantly better than the current OSHA definition.

Audiometry, Pure-Tone↗
PubMed1991

Cloning and functional characterization of the rat glutamine synthetase gene.

Glutamine synthetase catalyzes the formation of glutamine from glutamate and ammonia. It plays a central role in both amino acid neurotransmitter metabolism and ammonia detoxification in the central nervous system. Glutamine synthetase expression is regulated in developmental, hormonal, and in tissue- and cell-specific manners. We have cloned a full-length cDNA coding for rat glutamine synthetase, and have found an AT-rich area of conservation in the 3' untranslated regions between rat, mouse, and chicken, which may play a part in the regulation of the stability of the glutamine synthetase message. We have also cloned and mapped the gene coding for rat glutamine synthetase, and identified, by sequence analysis, areas potentially important for the regulation of glutamine synthetase transcription. Transient transfection of a variety of cell lines with deletion constructs of the glutamine synthetase promoter driving a chloramphenicol acetyltransferase reporter gene functionally demonstrates regions of the promoter containing elements important for transcriptional regulation.

Amino Acid Sequence↗
PubMed2000

Genetic structure of Proclossiana eunomia populations at the regional scale (Lepidoptera, nymphalidae).

Populations of Proclossiana eunomia (Lepidoptera, Nymphalidae) occur in middle Europe in patchy habitats of hay meadows along valleys or peat bogs. Samples of P. eunomia populations from the Ardennes region (northern France and southern Belgium) were analysed by allozyme electrophoresis. Patches isolated by more than 2 km of mature forests proved genetically distinct from their neighbouring populations. Mantel tests and regression analysis showed that the degree of genetic differentiation between the 26 studied populations is related to the geographical distances between them. Autocorrelation analysis (Moran's I ) showed that allele frequencies are positively correlated for populations up to 13 km apart and that the genetic neighbourhood of individuals is in the range of 0.9 km, which is in accordance with movement studies in this species conducted in the same area. Analysis using Wright's F-statistics revealed that the highest differentiation occurs between populations of the same subregion, whereas the whole Ardennes region is not genetically partitioned into subregions. This is probably because the connectivity of the network of suitable habitats has significantly weakened only since the 1950s, and thus subregional differentiation has not yet occurred.

Animals↗
PubMed1983

Identification of epitopes on the E glycoprotein of Saint Louis encephalitis virus using monoclonal antibodies.

Twenty-one hybridomas producing monoclonal antibodies specific for the E glycoprotein of St. Louis encephalitis (SLE) virus, strain MSI-7, have been isolated. Serologic reactivities were initially determined by cross-reactivity indirect immunofluorescence assays using 22 strains of SLE virus and 8 other related flaviviruses. Four groups demonstrating type-, subcomplex-, supercomplex-, and group-specific reactivity patterns were identified. Analysis of hemagglutination-inhibition (HI) and virus neutralization (N) subdivided the cross-reactivity groups into eight epitopes (E-1a,b,c,d, E-2, E-3, and E-4a,b). The antibodies could detect strain differences between SLE viruses isolated from various geographic areas. Analysis of the spatial arrangements of these epitopes using competitive binding assays with representative antibodies possessing similar binding avidities, indicated that the protein was a continuum of six overlapping domains.

Antibodies, Monoclonal↗
PubMed2004

Mass spectrometric imaging of lipids in brain tissue.

The spatial distributions of various specific lipids in freeze-dried mouse brain sections were monitored using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Mouse brain sections were prepared by cryosectioning, rinsing in 0.15 M NH3HCOO, and freeze-drying, after which the samples were analyzed directly by TOF-SIMS, using Au3+ ions as primary ions. Positive and negative TOF-SIMS spectra of the tissue surface contained peaks from quasimolecular ions of a variety of specific lipids, including cholesterol, sulfatides, phosphatidylinositols, and phosphatidylcholines. Images showing the spatial signal intensity distributions of specific ions were recorded across analysis areas ranging from 100 x 100 microm(2) to 9 x 9 mm(2). The results demonstrate a highly complementary localization of cholesterol and phosphatidylcholine over dimensions from millimeter to micrometer range. Characteristic spatial distributions of several other lipids, including sulfatides and phosphatidylinositols, were observed. Principal component analysis was used to localize regions of the sample surface that show common spectral features. Spectra from different such regions showed large variations in lipid ion signals, indicating large variations in the lipid composition in different regions.

Animals↗
PubMed2002

Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology.

PURPOSE: To develop and demonstrate a novel particle engineering technology, spray freezing into liquid (SFL), to enhance the dissolution rates of poorly water-soluble active pharmaceutical ingredients (APIs). METHODS: Model APIs, danazol or carbamazepine with or without excipients, were dissolved in a tetrahydrofuran/water cosolvent system and atomized through a nozzle beneath the surface of liquid nitrogen to produce small frozen droplets, which were subsequently lyophilized. The physicochemical properties of the SFL powders and controls were characterized by X-ray diffraction, scanning electron microscopy (SEM), particle size distribution, surface area analysis, contact angle measurement, and dissolution. RESULTS: The X-ray diffraction pattern indicated that SFL powders containing either danazol or carbamazepine were amorphous. SEM micrographs indicated that SFL particles were highly porous. The mean particle diameter of SFL carbamazepine/SLS powder was about 7 microm. The surface area of SFL danazol/poloxamer 407 powder was 11.04 m2/g. The dissolution of SFL danazol/poloxamer 407 powder at 10 min was about 99%. The SFL powders were free flowing and had good physical and chemical stability after being stored at 25 degrees C/60%RH for 2 months. CONCLUSIONS: The novel SFL technology was demonstrated to produce nanostructured amorphous highly porous particles of poorly water soluble APIs with significantly enhanced wetting and dissolution rates.

Drug Compounding↗
PubMed1986

The use of zip coded population data in social area studies of service utilization.

Social area analysis (SAA) is a well-established methodology for geographically based analysis of service delivery and other health related outcome measures. However, SAA has been limited in application by the complexities of computerized geocoding and difficulties in obtaining appropriate measures of community characteristics. In this paper we demonstrate that these problems can be overcome by employing zip code as well as the unit of analysis for SAA and obtaining commercially available measures of community characteristics. Regression analyses, using New York City zip code populations as the unit of observation were used to illustrate the role of epidemiologic risk factors in predicting rates of inpatient discharge and ambulatory care visits.

Ambulatory Care↗
PubMed1994

Metal dispersion and transportational activities using food crops as biomonitors.

The multielement (Al, Ca, Cd, Ce, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Si, and Zn) levels of various common vegetables (bean, broccoli, cabbage, cauliflower, lettuce, marrow, onion, parsnip, spinach, sprouts, sweet corn, and tomato); fruits (grape and strawberry); herbs (garlic, lemon balm, marjoram, mint, rosemary and tarragon); local pasture species and surface soils collected from a commercial garden centre located within a distance of 30 m of the London Orbital Motorway (M25) is presented. Comparative values are given from a background area, namely a domestic garden located in the North Yorkshire Dales National Park area. Analysis was undertaken by inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma-source mass spectrometry (ICP-MS) with quality control assessment using four international biological reference materials; BCR:CRM 62 Olive Leaves, NIST 1575 Pine Needles, NIST 1573 Tomato Leaves, and NIST 1572 Citrus Leaves. Inter-analytical method comparison is given using two methods of ICP-MS; namely conventional pneumatic nebulisation of sample solution, and direct solids analysis by laser ablation; and neutron activation analysis methods (NAA). For the elements listed there is a good precision obtained by ICP-MS and NAA. In particular levels of < +/- 1-10% (rsd) are obtained. Comparison of data with certified values and other analytical methods are generally of very good agreement. Lead levels in background areas ranged from 0.0008 to 0.340 microgram/g (fresh weight) for plant material; with the lead magnitude greater for grasses > herbs > vegetables > cereals > fruits. Measured values are in good agreement with reported literature values. The lowest Pb values are for marrow, lettuce, tomato and sweet corn samples (approximately 0.001-0.021 microgram/g). 'Green' leaf material levels were approximately 0.02-0.10 microgram/g (i.e. sprouts and cabbage). Root vegetables contain higher levels, approximately 0.02-0.125 microgram/g (especially carrot), reflecting possible metal uptake from soil. The highest vegetable Pb values are for leek and onion (approximately 0.35 microgram/g). Background values are also provided for nineteen elements (Al, As, B, Ba, Br, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Rb, Se, Sr, V, and Zn). Exposure to motor vehicle activities at a site some 30 m from the M25 shows only significant increases in Pb for unwashed plant material and surface soils. Typically Pb levels of 40-80% can be removed by washing plant surfaces resulting in metal levels similar to background areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants↗
PubMed1990

[Influence of metal elements in Pd alloys on the bonding to porcelain].

The influence of metal elements in three Pd alloys on the bonding to porcelain was examined. The high-temperature oxidation behavior of metal elements in alloys, structure and morphology of oxidation zones on the alloy surface and the appearance of bonding between alloy and fused porcelain at the interface were studied by ESCA and EPMA. From ESCA analysis, metal oxides such as PdO, SnO2, In2O3, CuO or Cu2O, Sb2O3 or Sb2O5 were formed on the surface of the alloy after degassing (preheating) and heating following casting. The amount of metal elements concentrated on the alloy surface was measured by their characteristic X-rays using area analysis of EPMA under the technical conditions of A) Acc. voltage 10 kV, Abs. current 40 nA, and B) Acc. voltage 20 kV, Abs. current 10 nA. Consequently, the amount of additive metal elements concentrated on the alloy surface which was detected in condition A) was larger than that detected in condition B). However, the amount of main element (Pd) concentrated on the alloy surface which was detected in condition A) was smaller than that detected in condition B). From the EPMA observation of the interface between alloy and fused porcelain, cross-section of alloys showed that the additive metal elements were oxidized in the alloy matrix, forming an internal oxide layer or particles. The structure and morphology of oxidation zones showed a significant difference between degassed and not-degassed alloys. Cross-sections inclined approximately 5 degrees 43' to the fusing boundary were also analyzed to enlarge the oxidation zones. This analytical technique effectively revealed the structure and morphology of oxidation zones. In conclusion, not only additive metal elements but also the main element at the surface of alloys play important roles on the bonding to porcelain. Degassing of the alloy was considered to an essential procedure to obtain the adequate bonding to porcelain.

Dental Bonding↗
PubMed1996

Decreased expression of placental growth hormone in intrauterine growth retardation.

During normal pregnancy, the levels of placental GH in the maternal circulation increase significantly until 35 wk of gestation. We have previously shown that these levels are significantly reduced in cases of intrauterine growth retardation (IUGR). To better understand the basis of this observation, we have studied the expression of placental GH in placentas from normal births (n = 6) and births with IUGR (n = 5). In situ hybridization histochemistry was used to determine the mean number of cells per area expressing this message, as well as the mean level of specific mRNA per cell. We have found that the mean mRNA signal level per cell of placental GH did not differ between normal or IUGR placentas. However, the mean number of cells/ area expressing this mRNA was significantly greater in normal placentas compared with IUGR placentas (normal 12.8 +/- 0.9 cells/unit area, IUGR 4.9 +/- 2.4 cells/unit area, analysis of variance: p < 0.004). These data suggest that the decreased levels of placental GH in the maternal circulation in IUGR are not due only to the reduced size of the placenta, but also to changes in the placental tissue which result in a reduced number of cells per area that are capable of producing this peptide.

Female↗
PubMed2002

Bioconcentration of metals in the moss Scleropodium purum in the area surrounding a power plant. A geotopographical predictive model for mercury.

Samples of the moss Scleropodium purum collected in 1995 and 1997 were used to biomonitor the deposition of metals in the area surrounding a thermal power plant. Significantly higher levels of Cu (p < 0.05), Fe (p < 0.01), As and Hg (p < 0.001) were found in the 1997 samples than in the 1995 samples, due to changes in atmospheric conditions. The influence on bioconcentration of the orientation of the sampling sites relative to the source of emission was studied. It was found that the increase recorded in 1997 generally occurred in the sampling sites in the south east of the study area. Analysis of the effect of distance from the source of emission revealed that the increase in metal levels in 1997 took place close to the power station (10-30 km). Finally, multiple regression analysis was used to construct a model that related different topographical variables to the concentrations of Hg in moss. The model, constructed using the data collected in both sampling periods, included the orientation of the sampling sites relative to the source of emission as well as the height of sampling sites in 1995 and the distance from the emission point in 1997. The model allowed us to determine the extent of the area affected by deposition and to establish the magnitude of deposition.

Air Pollutants↗
PubMed2003

Limited evolution of West Nile virus has occurred during its southwesterly spread in the United States.

Analysis of partial nucleotide sequences of nine West Nile virus strains isolated in southeast Texas during June-August 2002 revealed a maximum of 0.35% nucleotide variation from a New York 1999 strain. Two sequence subtypes were identified that differed from each other by approximately 0.5%, suggesting multiple introductions of virus to this area. Analysis of sequences from cloned PCR products for one strain revealed up to 0.6% divergence from the consensus sequence at the subpopulation level. The presence of unique patterns of small numbers of mutations in North American West Nile strains studied to date may suggest the absence of a strong selective pressure to drive the emergence of dominant variants.

Animals↗
PubMed1986

A community-based analysis of ambulatory surgery utilization.

We conducted a study to determine the utilization level for ambulatory surgery and the proportions of specific procedures which could be performed in certain ambulatory settings in one community, Syracuse, New York, which has used this service extensively. It was estimated that, in 1983, 26.9 surgery cases per 1,000 population in Syracuse were performed in ambulatory settings. This level amounted to approximately 37 per cent of hospital-based surgery in the area. Analysis of surgery utilization in two hospital-integrated and freestanding ambulatory surgery facilities indicated that more than 95 per cent of myringotomies, tonsillectomies, and adenoidectomies as well as substantial proportions of carpal tunnel releases, lens extractions, sterilizations, circumcisions, and inguinal hernia repairs in these two facilities were performed in ambulatory settings. The availability of dedicated facilities and full-time staff produced higher utilization for these procedures in freestanding facilities. The utilization levels for individual procedures identified in the study can be employed in the planning of hospital-integrated and freestanding programs.

Adenoidectomy↗
PubMed2005

Brain activation during encoding and recognition of verbal and figural information in older adults.

Positron emission tomography (PET) patterns of cerebral blood flow associated with verbal and figural memory are described in relation to their value as functional probes for studying longitudinal changes that occur in the aging brain. Relative to a matching control task, verbal and figural encoding increase blood flow in prefrontal cortex (PFC), anterior cingulate, insular, lateral and medial temporal, occipital cortex and the cerebellum. Additionally, medial temporal regions exhibited greater activity during figural encoding relative to verbal encoding. During recognition, blood flow increases in prefrontal, cingulate, insular, and lateral temporal and Broca's areas. Analysis of hemispheric asymmetry reveals that the prefrontal cortex exhibits regionally dependent results. Prefrontal region BA 10 demonstrates more bilateral activation during encoding and retrieval, whereas BA 46 shows right greater than left activation during both encoding and retrieval. Overall, the two tasks activate diverse regions within the frontal, temporal and occipital lobes of the brain, including areas that show age-related structural changes, proving their usefulness in the longitudinal assessment of brain function in the elderly.

Aged↗
PubMed2005

Non-linear mapping for exploratory data analysis in functional genomics.

BACKGROUND: Several supervised and unsupervised learning tools are available to classify functional genomics data. However, relatively less attention has been given to exploratory, visualisation-driven approaches. Such approaches should satisfy the following factors: Support for intuitive cluster visualisation, user-friendly and robust application, computational efficiency and generation of biologically meaningful outcomes. This research assesses a relaxation method for non-linear mapping that addresses these concerns. Its applications to gene expression and protein-protein interaction data analyses are investigated. RESULTS: Publicly available expression data originating from leukaemia, round blue-cell tumours and Parkinson disease studies were analysed. The method distinguished relevant clusters and critical analysis areas. The system does not require assumptions about the inherent class structure of the data, its mapping process is controlled by only one parameter and the resulting transformations offer intuitive, meaningful visual displays. Comparisons with traditional mapping models are presented. As a way of promoting potential, alternative applications of the methodology presented, an example of exploratory data analysis of interactome networks is illustrated. Data from the C. elegans interactome were analysed. Results suggest that this method might represent an effective solution for detecting key network hubs and for clustering biologically meaningful groups of proteins. CONCLUSION: A relaxation method for non-linear mapping provided the basis for visualisation-driven analyses using different types of data. This study indicates that such a system may represent a user-friendly and robust approach to exploratory data analysis. It may allow users to gain better insights into the underlying data structure, detect potential outliers and assess assumptions about the cluster composition of the data.

Algorithms↗
PubMed1993

Morphometric, DNA and PCNA in thin malignant melanomas.

Morphometric assessment of nuclear area, shape and density, nucleolar area, analysis of DNA content and expression of proliferating cell nuclear antigen (PCNA) was performed in a case control study of 72 malignant melanomas, thickness < or = 0.8 mm and Clark level II-III. Twenty-four thin metastasizing melanomas (TMM) were individually compared to two thin non-metastasizing melanomas (TNM) after individual matching for site of primary tumor, tumor thickness, level of invasion, tumor regression and duration of follow-up. Conditional logistic regression analysis with maximum likelihood estimates showed significant differences between TMM and TNM with regard to the nuclear correlation coefficient (p = 0.005), standard deviation of nuclear shape NCI (p = 0.017), and nuclear density (p = 0.030), indicating that thin melanomas with pleomorphic and possibly densely packed nuclei are associated with recurrence. No significant differences were found regarding nuclear or nucleolar area, mean nuclear shape NCI, nuclear DNA content or expression of PCNA.

Antigens, Neoplasm↗
PubMedDate not supplied

Effect of 12 months of recombinant human growth hormone replacement therapy on insulin sensitivity in GH-deficient adults as determined by different methods.

BACKGROUND: Controversial results have been obtained in measuring insulin sensitivity (S(I)) during recombinant human growth hormone (rhGH) treatment in adult growth hormone deficient (GH-deficient) patients. AIMS: The aim of our study was to estimate S(I) before and during treatment using three different methods for quantifying insulin sensitivity in GH-deficient adults treated with rhGH. SETTINGS AND DESIGN: Twenty-one GH-deficient adults were treated with rhGH during 12 months. S(I) was estimated using Minimal model analysis, Homeostatic Model of Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) before and after 3, 6, 9 and 12 months of rhGH therapy. MATERIAL AND METHODS: Oral Glucose Tolerance Test (OGTT) and Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) were performed in each patient at respective time intervals. QUICKI and HOMA were calculated using basal values of glucose and insulin from FSIGT. Minimal model computer analysis was calculated from glucose and insulin data obtained during FSIGT. STATISTICAL ANALYSIS: Area under the curve for glucose, insulin and C-peptide were calculated using trapezoidal rule from OGTT data. Differences and correlations were tested using ANOVA for repeated measures, Wilcoxon's matched-paired test, paired t-test, Pearson's correlation and Bland Altman plot. RESULTS: There were no significant changes in S(I) using Minimal model analysis and QUICKI during rhGH treatment. On the contrary, HOMA analysis indicated significant deterioration in S(I) after 12 months of therapy. CONCLUSION: Our study did not demonstrate any changes in S(I) using Minimal model and QUICKI analysis, while there was significant increase in insulin resistance using HOMA model. We suggest that the choice of method for the determination of S(I) may influence the interpretation of results concerning the effect of rhGH therapy on S(I) in GH-deficient adults.

Adult↗