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Temporal variation in incidence of IDDM in Canterbury, New Zealand.

OBJECTIVES: To establish the statistical significance of observed variations over the last decade in the incidence of insulin-dependent diabetes mellitus (IDDM) in the 0- to 19-yr-old age-group and to determine whether incidence has increased in Canterbury, New Zealand. RESEARCH DESIGN AND METHODS: The Canterbury, New Zealand, Diabetes Registry has recorded all incidence cases of diabetes mellitus prospectively since 1982. All IDDM subjects aged 0-19 yr at diagnosis and using insulin are included in the study. Ascertainment is believed to be 100%. Prevalence was recorded at 1 January 1982 and 1 January 1990. Annual incidence for 1982-1990 was determined using age and sex cross-sectional census population denominators. The statistical significance of temporal, age, sex, and seasonal variations in incidence rates was ascertained by Poisson regression models (GLIM statistical software). RESULTS: Prevalence on 1 January 1990 was 115/100,000. Incidence rates during the 9 yr were periodic, with two major peaks--one in the early 1980s, the other in 1989 continuing into 1990. The temporal variation (P less than 0.02) was not age or sex specific. Incidence rates for boys were three- to fourfold higher during peak versus trough years, with a peak level of 20.7/100,000 in 1990. For girls, there was less variation, with a peak rate of 21.6/100,000 in 1990. There has been no significant increase in IDDM incidence over time. The mean rate of incidence across all age-groups for 1982-1990 was 12.7/100,000 person-yr. A significant seasonal association to the onset of IDDM was found only in boys, with incidence rates being significantly higher in winter than in summer (P less than 0.01). CONCLUSIONS: IDDM in Canterbury, New Zealand, presents in cycles of incidence peaks and troughs, each spanning 2-3 yr.

Adolescent↗

Interstellar solid CO: polar and nonpolar interstellar ices.

We present moderate-resolution (lambda/delta lambda approximately 1200) observations of the solid CO band in a sample of protostars. The spectra reveal two independent solid CO components along most lines of sight. One produces a narrow (delta nu approximately 5 cm-1) band generally centered at about 2140 cm-1 and the other a broader (delta nu approximately 10 cm-1) one at about 2136 cm-1. Both the peak position and width of the narrow, and generally strongest, component vary from object to object. The relative strengths of the two components vary considerably in this sample. Laboratory studies of the shape and peak position of the solid CO banD in astrophysically relevant mixtures show that the narrow CO band occurs in mixtures dominated by non-polar molecules (e.g., CO itself, CO2, O2, N2), while the broad feature is due to more polar mixtures, such as H2O ice. Calculations show that for mixtures dominated by CO (CO concentration > 0.3), the peak position and shape of the CO fundamental are strongly influenced by "surface modes," while for lower concentrations the laboratory measured absorption spectra provide very accurate representations of the small particle extinction spectrum. The observed variations in peak position and width of the interstellar 2140 cm-1 component can be attributed to variations in composition and/or physical characteristics of the grains (i.e., shape). These observations show that many lines of sight contain (at least) two independent grain mantle components: a polar mixture (H2O-rich) responsible for the 3.08 and 6.0 micrometers ice bands and a nonpolar one dominating the solid CO spectrum. These two independent grain mantle components may reflect chemical variations during accretion. Around luminous protostars, differences in volatility of the nonpolar and H2O-rich ices also may play an important role in determining their relative abundances.

Astronomical Phenomena↗

Model assessment of biogeochemical controls on dissolved organic carbon partitioning in an acid organic soil.

A chemical model (constructed in the ORCHESTRA modeling framework) of an organic soil horizon was used to describe soil solution data (10 cm depth) and assess if seasonal variations in soil solution dissolved organic carbon (DOC) could be explained by purely abiotic (geochemical controls) mechanisms or whether factors related to biological activity are needed. The NICA-Donnan equation is used to describe the competitive binding of protons and cations and the charge on soil organic matter. Controls on organic matter solubility are surface charge and a parameter, gamma, that accounts for the distribution of humic molecules between hydrophobic and hydrophilic fractions. Calculations show that the variations in solute chemistry alone are not sufficient to account for the observed variations of DOC, but factors that alter gamma, such as biological activity, are. Assuming that DOC in organic soils is derived from soluble humic material and that gamma is modified seasonally due to biological activity (with monthly soil temperature used as a surrogate for biological activity) we are able to model the observed seasonality of soil solution DOC over a 10-year period. Furthermore, with modeled DOC coupled to other geochemical processes we also model soil solution pH and Al concentrations.

Carbon↗

Optical density variations and microscopic observations in the evaluation of platelet shape change and microaggregate formation.

Addition of Ristocetin to formalin-fixed platelets suspended in diluted PPP induces a marked increase in turbidity which is not caused by platelet shape change but by the formation of microaggregates. If diluted PPP of patients with severe von Willebrand's disease is used, only an initial increase in turbidity and no further decrease is observed without any form variation of the platelets but again with formation of many microaggregates. In normal PRP diluted with buffered EDTA, ADP induces an increase in turbidity without further changes in optical density. Simultaneously platelets immediately change their shape with formation of pseudopodia and sphering but at the same time also microaggregates appear. Shape change and microaggregate formation can also be observed after the addition of Collagen to undiluted PRP which is followed by the formation of large aggregates and a decrease in optical density. Increase in optical density in undiluted PRP is not a specific indicator of platelet shape changes. Microaggregates can alone or partially be responsible for these changes. For the evaluation of platelet shape changes but also for the estimation of microaggregate formation microscopic methods are preferred.

Adenosine Diphosphate↗

Maximizing the detection capability of a beet western yellows virus ELISA system.

Conditions for maximizing detection of a California isolate of beet western yellows virus (BWYV) were investigated with the double-sandwich enzyme-linked immunosorbent assay (ELISA) system. Within-plate variability was found to account for less than 1% of the total variation observed on individual microtiter plates. Variability across plates was greater than within plates and accounted for less than 10% of the total variation. Significant reductions in absorbance were observed when either coating or conjugated IgGs were incubated for 2 h at 37 degrees C. Incubation of coating IgGs overnight at 4 or 22 degrees C gave good results. No differences in absorbance were observed when antigen sources were incubated at 37, 22, or 4 degrees C. Absorbance at 1, 3 or 6 h incubation of conjugated IgGs at 4 or 22 degrees C was low to moderate but after 18 or 24 h absorbance was markedly increased without increasing background. Efficient extraction of virus from host and vector tissues increased absorbance. Carborundum added to the extraction buffer worked well when tissue samples were ground in a mortar and pestle but highest absorbance resulted when test samples were prepared with a high-speed tissue homogenizer. Background levels were unacceptably high when 10 or more Myzus persicae were pooled for analysis. Since virus can be detected in 3 or even 1 aphid, pooling for detection is unnecessary. Optimization of the BWYV ELISA system made possible the detection of virus quantities less than 2 ng/ml.

Antibodies, Viral↗

5-Hydroxyindoles compounds and nitric oxide voltammetric detection in the rat brain: changes occurring throughout the sleep-wake cycle.

The release of serotonin may occur throughout the sleep-wake cycle according to 2 different modalities: - by the axonal nerve endings during waking; - by the dendrites and/or the soma of the nucleus raphe dorsalis (nRD) during sleep. Neuronal nitric oxide (NO), synthesised by constitutive NO synthase (NOS), is colocalized with neurotransmitters such as GABA, acetylcholine, somatostatin, serotonin, etc. In order to evaluate its modalities of release throughout the rat sleep-wake cycle, a sensor allowing its specific detection in freely moving animals was prepared. In the cortex, the highest NO signal occurs during the waking state (W=100%) versus slow wave sleep (SWS=-6%) and paradoxical sleep (PS=-9%). The mild variations observed might reflect a mean of the individual sleep-wake cycle variations attached to each NO source (GABAergic interneurons, cholinergic and serotoninergic axonal nerve endings, etc.).

Animals↗

The stream and its altered valley: integrating landscape ecology into environmental assessments of agro-ecosystems.

Little is known about the importance of landscape and land cover to the implementation and performance of agricultural conservation projects designed to improve stream quality. In our study, we addressed the potential importance of landscape and land cover to conservation projects by measuring variation across 191 mu-basins (100-2400 ha) and integrating the observed variation into a study design aimed at determining the effectiveness of conservation projects. Our findings indicate that there are strong gradients across which landscape and land cover attributes vary. Land cover varied along a gradient of agricultural intensity, basin morphometry across gradients of stream closure and basin size, basin substrate was described by variation in drumlin formation, glacial landform type, and soil drainage, while agricultural conservation projects varied according to the level of project implementation. Correlation of these gradients found several associations between landscape and land cover, indicating that agricultural intensity was being constrained predominantly by drumlin formation and glacial landform type. Landscape and land cover did not appear to be determining factors in the implementation of conservation projects by land owners. Based on these findings we chose 32 mu-basins which represented the variability along each of the defined gradients for further study. We conclude that landscape scale variables demonstrate important variation and covariation that can and should be integrated into study designs for the assessment of streams and human activities affecting streams.

Agriculture↗

Differential measurement of constitutive (COX-1) and inducible (COX-2) cyclooxygenase expression in human umbilical vein endothelial cells using specific immunometric enzyme immunoassays.

We have produced and characterized monoclonal antibodies (mAbs) directed against a specific carboxyterminal sequence of human cyclooxygenase-2 (residues 580-598). A rabbit polyclonal antiserum was also raised against another sequence of 10 amino acids (residues 570-581) not present in human constitutive cyclooxygenase-1. Affinity-purified polyclonal antibodies, coated on microtiter plates, were used as capture antibodies in a two-site immunometric assay, with an mAb-acetylcholinesterase conjugate used as tracer. The detection limit was 500 fmol/ml of peptide C3-COX2 (residues 570-595). The assay was specific for the cyclooxygenase-2 (COX-2) isoform, since no immunoreactivity could be detected in platelet extracts known to be rich in cyclooxygenase-1 (COX-1). In contrast, extracts from cultured human umbilical vein endothelial cells challenged with 20 nM phorbol myristate acetate (PMA) showed an increase in COX-2 immunoreactivity related both to the increase in enzyme activity and the variations observed by Western blot analysis. Under these conditions, analysis of the same cell lysates with another immunometric assay specific for COX-1 revealed insignificant variation of this enzyme. The specificity of detection was further assessed by measuring the immunoreactivity of the fractions obtained after molecular sieve chromatography of control and stimulated cell extracts, and corroborated the marked enhancement of COX-2 by comparison with COX-1. Treatment of PMA-activated cells with H-7 or actinomycin D totally abolished the COX-2 signal and had little effect on COX-1. No significant variation in COX-2 immunoreactivity was observed using the inactive isomer 4 alpha-PMA, even at 100 nM. These assays constitute the first quantitative analysis of constitutive COX-1 and of inducible COX-2 in nucleated cells at the protein level.

Amino Acid Sequence↗

Relationship between blood pressure and in vivo action of insulin in type II (non-insulin-dependent) diabetic subjects.

In nondiabetic hypertensive subjects, a relationship has been found between insulin resistance and level of blood pressure. Since type II (non-insulin-dependent) diabetic subjects are often both insulin-resistant and hypertensive, we studied the relationship between insulin resistance and blood pressure level in a group of patients with type II diabetes. Fourteen women and 19 men with diabetes for 2 to 14 (mean, 7.4) years, treated with diet alone (five subjects) or combined with hypoglycemic agents, were studied. Their average hemoglobin A1c (HbA1c) levels during the study period were 6.6% to 11.7% (mean, 8.6%), and their body mass indexes (BMI) were 20.8 to 33.1 (mean, 26.3) kg/m2. Insulin sensitivity was measured using the hyperinsulinemic, euglycemic glucose clamp technique, and an insulin-sensitivity index was calculated as the ratio of the glucose disposal rate (GDR) to the insulin concentration during clamp (GDR/I). The average of three to eight measurements of diastolic blood pressure (DBP) during the study period (9 to 24 months) in each subject was 79 to 111 (mean, 95.1) mm Hg, and DBP also showed significant correlations to BMI (r = .54) and fasting C-peptide level (r = .38). In a multiple regression model, GDR/I, antihypertensive treatment, and known duration of diabetes were significant and independent predictors of variations in blood pressure, and GDR/I could account for 35% of the observed variations in DBP. We conclude that, in accordance with what has been found in nondiabetic hypertensives, DBP correlates significantly to insulin resistance in type II diabetic subjects.

Antihypertensive Agents↗

Geographic analysis of diabetes prevalence in an urban area.

The objective of this research is to identify the sociodemographic, environmental, and lifestyle factors associated with the geographic variability of Diabetes Mellitus (DM) prevalence in the City of Winnipeg, Manitoba in Canada. An ecological regression study design was employed for this purpose. The study population included all prevalent cases of DM in 1998 for Winnipeg. Predictor and outcome data were aggregated for analysis using two methods. First, the spatial scan statistic was used to aggregate study data into highly probable diabetes prevalence clusters. Secondly, predictor and outcome data were aggregated to existing administrative health areas. Analysis of variance and spatial and non-spatial linear regression techniques were used to explore the relationship between predictor and outcome variables. The results of the two methods of data aggregation on regression results were compared. Mapping and statistical analysis revealed substantial clustering and small-area variations in the prevalence of DM in the City of Winnipeg. The observed variations were associated with variations in socioeconomic, environmental and lifestyle characteristics of the population. The two methods of data aggregation used in the study generated very similar results in terms of identifying the geographic location of DM clusters and of the population characteristics ecologically correlated to those clusters. High rates of DM prevalence are strongly correlated with indicators of low socioeconomic status, poor environmental quality and poor lifestyles. This analysis further illustrates what a useful tool the spatial scan statistic can be when used in conjunction with ecological regression to explore the etiology of chronic disease.

Analysis of Variance↗

A density functional study of uranyl monocarboxylates.

We studied uranium(VI) monocarboxylate complexes by a relativistic density functional method using simple carboxylic acids as ligands, i.e. [UO2(OOCR)]+ (R = H, CH3, CH2CH3). These complexes exist in aqueous solution and, for R = CH3 and CH2CH3, may also be considered as models of uranyl complexated by humic substances. We investigated mono- and bidentate coordination modes. Short-range solvent effects were accounted for explicitly via aqua ligands of the first hydration shell and long-range electrostatic interactions were described via a polarizable continuum model. The calculated results for the uranyl U=O bond, the bond to aqua ligands, and the averaged uranium distances to equatorial oxygen atoms, U-Oeq, agreed quite well with EXAFS-derived interatomic distances. However, the uranyl-carboxylate bond was calculated to be notably shorter than the experimentally determined value. Experimental differences between mono- and bidentate coordination, obtained mainly from crystal structures, were qualitatively reproduced for the U-C distance but not for the average bond length, U-Oeq. We discuss these discrepancies between calculated and experimental results in some detail and suggest changes in the coordination number rather than variations of the coordination geometry as the main source of the experimentally observed variation of the U-Oeq distance.

Carboxylic Acids↗

Reliability and reproducibility of clinical findings in low-back pain.

The data obtained from the history and examination of patients with low-back pain and sciatica have been subjected to an observer variation analysis. Redesign of the proformata resulted in a reduction of the observer error from 33% to 18% for the history, but no improvement in the finding of a 30% observer error in the examination. The clinician has a simple choice: if he wishes to obtain a large amount of detailed information he must realize that much of it will be unreliable; if he is prepared to limit the information then he will increase its reliability.

Back Pain↗

Microsatellite analysis of population structure in Canadian polar bears.

Attempts to study the genetic population structure of large mammals are often hampered by the low levels of genetic variation observed in these species. Polar bears have particularly low levels of genetic variation with the result that their genetic population structure has been intractable. We describe the use of eight hypervariable microsatellite loci to study the genetic relationships between four Canadian polar bear populations: the northern Beaufort Sea, southern Beaufort Sea, western Hudson Bay, and Davis Strait-Labrador Sea. These markers detected considerable genetic variation, with average heterozygosity near 60% within each population. Interpopulation differences in allele frequency distribution were significant between all pairs of populations, including two adjacent populations in the Beaufort Sea. Measures of genetic distance reflect the geographic distribution of populations, but also suggest patterns of gene flow which are not obvious from geography and may reflect movement patterns of these animals. Distribution of variation is sufficiently different between the Beaufort Sea populations and the two more eastern ones that the region of origin for a given sample can be predicted based on its expected genotype frequency using an assignment test. These data indicate that gene flow between local populations is restricted despite the long-distance seasonal movements undertaken by polar bears.

Animals↗

Fundamental precision limitations for measurements of frequency dependence of backscatter: applications in tissue-mimicking phantoms and trabecular bone.

Various models for ultrasonic scattering from trabecular bone have been proposed. They may be evaluated to a certain extent by comparison with experimental measurements. In order to appreciate limitations of these comparisons, it is important to understand measurement precision. In this article, an approach proposed by Lizzi and co-workers is adapted to model precision of estimates of frequency-dependent backscatter for scattering targets (such as trabecular bone) that contain many scatterers per resolution cell. This approach predicts uncertainties in backscatter due to the random nature of the interference of echoes from individual scatterers as they are summed at the receiver. The model is validated in experiments on a soft-tissue-mimicking phantom and on 24 human calcaneus samples interrogated in vitro. It is found that while random interference effects only partially explain measured variations in the magnitude of backscatter, they are virtually entirely responsible for observed variations in the frequency dependence (exponent of a power law fit) of backscatter.

Bone Density↗

Bacterial alkaline phosphatase clonal variation in some Escherichia coli K-12 phoR mutant strains.

Several phoR alleles (phoR19, phoR20, phoR68, phoR69, phoR70, and phoR78) led to either a bacterial alkaline phosphatase (BAP)-constitutive phenotype or a variable behavior, depending upon the strain tested. Whereas Escherichia coli K10, MC1000, and XPh4 phoR mutants were constitutive, AB1157, BD792, MC4100, and W3110 phoR mutants displayed the metastable character. For the latter strains, constitutive mutants regularly segregated BAP-negative clones which yielded constitutive variants again at a high frequency. Indeed, the pattern of variation observed in BAP-variable phoR strains is phenotypically analogous to phase variation of the H1/H2 flagellum antigen type in Salmonella typhimurium and the molecular switch between the immune and sensitive states in bacteriophage lambda. The metastable behavior was not a general property of BAP-constitutive mutants, since several phosphate-specific transport-phoU mutations led to a constitutive (stable) phenotype regardless of the strain tested. But in phoR phosphate-specific transport-phoU mutants, the metastable character was epistatic (dominant), and such double mutants showed clonal variation in BAP-variable strains.

Alkaline Phosphatase↗

Markers for estimating digesta flow in pigs and the effects of dietary fiber.

Effects of diluting the energy content of a corn-soybean meal diet with either alfalfa meal or corn cobs on nutrient digestibility and rate of passage of feed residues and particle markers were measured in crossbred (Yorkshire X Landrace X Chester White X Large White) barrows with a mean body weight of about 80 kg. The excretion pattern in the feces of Cr-mordanted diet and of rare earths initially bound individually to the mixed diet or to the corn or soybean meal suggested a model having a single age-dependent compartment with time delay. The compartmental turnover rate parameter (lambda 1) estimated by this model did not differ for the rare earths individually used to mark the corn-soybean meal diet (Yb), the corn (La) or the soybean meal (Sm). In contrast, lambda 1 for Cr was smaller (P less than .001) than that of the mean for the three rare earths. The residence time due to displacement flow (tau) did not differ among markers. These results were interpreted to indicate that the high specific gravity of Cr-mordanted feed slowed flow due to mixing but not due to displacement. Correlations between lambda 1 and tau were less than .71. These results suggested that the flow of rare earths initially bound to feed ingredients provides a reasonable estimate of the flow of their undigested residues through the gastrointestinal tracts of nonruminant animals. Inclusion of the fibrous feeds reduced digestibility of dry matter, cell contents, crude protein and acid detergent lignin and increased digestibility of cell walls, cellulose and acid detergent fiber. Digestibilities of cellulose and acid detergent fiber were greater with alfalfa than with corn cobs as the fiber source. Differences in digestibility of crude protein and acid detergent fiber existed due to litter in one replicate of the experiment. Variation in digestibility was not significantly related to variation in lambda 1 or tau within or among treatments and litters. This suggests that variations in lambda 1 and tau were not important causes of the observed variation in digestibility.

Animal Feed↗

Variation in the use of alternative levels of hospital care for newborns in a managed care organization.

OBJECTIVE(S): To assess the extent to which variation in the use of neonatal intensive care resources in a managed care organization is a consequence of variation in neonatal health risks and/or variation in the organization and delivery of medical care to newborns. STUDY DESIGN: Data were collected on a cohort of all births from four sites in Kaiser Permanente by retrospective medical chart abstraction of the birth admission. Likelihood of admission into a neonatal intensive care unit (NICU) is estimated by logistic regression. Durations of NICU stays and of hospital stay following birth are estimated by Cox proportional hazards regression. RESULTS: The likelihood of admission into NICU and the duration of both NICU care and hospital stay are proportional to the degree of illness and complexity of diagnosis. Adjusting for variation in health risks across sites, however, does not fully account for observed variation in NICU admission rates or for length of hospital stay. One site has a distinct pattern of high rates of NICU admissions; another site has a distinct pattern of low rates of NICU admission but long durations of hospital stay for full-term newborns following NICU admission as well as for all newborns managed in normal care nurseries. CONCLUSIONS: Substantial variations exist among sites in the risk-adjusted likelihood of NICU admission and in durations of NICU stay and hospital stay. Hospital and NICU affiliation (Kaiser Permanente versus contract) or affiliation of the neonatologists (Kaiser Permanente versus contract) could not explain the variation in use of alternative levels of hospital care. The best explanation for these variations in neonatal resource use appears to be the extent to which neonatology and pediatric practices differ in their policies with respect to the management of newborns of minimal to moderate illness.

Health Maintenance Organizations↗

[Importance and value of roentgen studies as outcome criteria in rheumatoid arthritis].

In order to evaluate the objectivity and validity of radiographic parameters in rheumatoid arthritis (RA) we studied 56 patients with definite RA. Inter-observer variation was assessed comparing the scorings (Larsen classification) of two independent experienced observers. Total radiographic scores were highly significantly correlated (r = 0.89). Yet, we could not find relevant associations between radiographic findings and clinical outcome parameters (pain, morning stiffness, dexterity, grip strength, and patient's overall assessment). Thus, hand radiographs in RA provide highly reproducible results. Its validity concerning patient outcome, however, has to be interpreted very carefully.

Adult↗