Oral glucose tolerance test in children and adolescents: Positives and pitfalls

Objectives: To describe the glycaemic status (assessed by an oral glucose tolerance test (OGTT)) and associated comorbidities in a cohort of Australian children and adolescents at risk of insulin resistance and impaired glucose homeostasis (IGH). Methods: Twenty-one children and adolescents (three male, 18 female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy) referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If abnormal, the OGTT was repeated. Results: The mean (SD) age was 14.2 (1.6) years, BMI 38.8 (7.0) kg/m(2) and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in one patient. Despite no weight loss, only one patient had a persistently abnormal OGTT on repeat testing. Three patients with IGH were medicated with risperidone at the time of the initial OGTT. One patient who had persistent IGT had continued risperidone. The other two patients had initial OGTT results of IGT and diabetes mellitus type 2. They both ceased risperidone between tests and repeat OGTT showed normal glycaemic status. Conclusions: Use of fasting glucose alone may miss cases of IGH. Diagnosis of IGT should not be made on one test alone. Interpretation of glucose and insulin responses in young people is limited by lack of normative data. Larger studies are needed to generate Australian screening recommendations. Further assessment of the potential adverse effects of atypical antipsychotic medication on glucose homeostasis in this at-risk group is important.

Disturbed microtubule function and induction of micronuclei by chelate complexes of mercury(II)

Interactions of mercury(II) with the microtubule network of cells may lead to genotoxicity. Complexation of mercury(II) with EDTA is currently being discussed for its employment in detoxification processes of polluted sites. This prompted us to re-evaluate the effects of such complexing agents on certain aspects of mercury toxicity, by examining the influences of mercury(H) complexes on tubulin assembly and kinesin-driven motility of microtubules. The genotoxic effects were studied using the micronucleus assay in V79 Chinese hamster fibroblasts. Mercury(II) complexes with EDTA and related chelators interfered dose-dependently with tubulin assembly and microtubule motility in vitro. The no-effect-concentration for assembly inhibition was 1muM of complexed Hg(II), and for inhibition of motility it was 0.05 muM, respectively. These findings are supported on the genotoxicity level by the results of the micronucleus assay, with micronuclei being induced dose-dependently starting at concentrations of about 0.05 muM of complexed Hg(II). Generally, the no-effect-concentrations for complexed mercury(II) found in the cell-free systems and in cellular assays (including the micronucleus test) were identical with or similar to results for mercury tested in the absence of chelators. This indicates that mercury(II) has a much higher affinity to sulfhydryls of cytoskeletal proteins than to this type of complexing agents. Therefore, the suitability of EDTA and related compounds for remediation of environmental mercury contamination or for other detoxification purposes involving mercury has to be questioned. (C) 2004 Elsevier B.V. All rights reserved.

Genotoxicity of inorganic mercury salts based on disturbed microtubule function

This study investigated the hypothesis that the chromosomal genotoxicity of inorganic mercury results from interaction(s) with cytoskeletal proteins. Effects of Hg2+ salts on functional activities of tubulin and kinesin were investigated by determining tubulin assembly and kinesin-driven motility in cell-free systems. Hg2+ inhibits microtubule assembly at concentrations above 1 muM, and inhibition is complete at about 10 muM. In this range, the tubulin assembly is fully ( up to 6 muM) or partially (similar to 6 - 10 muM) reversible. The inhibition of tubulin assembly by mercury is independent of the anion, chloride or nitrate. The no-observed-effect-concentration for inhibition of microtubule assembly in vitro was 1 muM Hg2+, the IC50 5.8 muM. Mercury(II) salts at the IC50 concentrations partly inhibiting tubulin assembly did not cause the formation of aberrant microtubule structures. Effects of mercury salts on the functionality of the microtubule motility apparatus were studied with the motor protein kinesin. By using a gliding assay'' mimicking intracellular movement and transport processes in vitro, HgCl2 affected the gliding velocity of paclitaxel-stabilised microtubules in a clear dose-dependent manner. An apparent effect is detected at a concentration of 0.1 muM and a complete inhibition is reached at 1 muM. Cytotoxicity of mercury chloride was studied in V79 cells using neutral red uptake, showing an influence above 17 muM HgCl2. Between 15 and 20 muM HgCl2 there was a steep increase in cell toxicity. Both mercury chloride and mercury nitrate induced micronuclei concentration-dependently, starting at concentrations above 0.01 muM. CREST analyses on micronuclei formation in V79 cells demonstrated both clastogenic (CREST-negative) and aneugenic effects of Hg2+, with some preponderance of aneugenicity. A morphological effect of high Hg2+ concentrations ( 100 muM HgCl2) on the microtubule cytoskeleton was verified in V79 cells by immuno-fluorescence staining. The overall data are consistent with the concept that the chromosomal genotoxicity could be due to interaction of Hg2+ with the motor protein kinesin mediating cellular transport processes. Interactions of Hg2+ with the tubulin shown by in vitro investigations could also partly influence intracellular microtubule functions leading, together with the effects on the kinesin, to an impaired chromosome distribution as shown by the micronucleus test.

Measurement of glass-rubber transition temperature of skim milk powder by static mechanical test

Stickiness behavior of skim milk powder was investigated based on the mechanical property of the material during the glass-rubber transition. A thermally controlled device was developed for the static mechanical test. This device was attached to a texture analyzer, and skim milk powder, which was used as a model sample, was tested for its glass-rubber transition temperature (Tg-r) using static compression technique (creep test). Changes in compression probe distance as a function of temperature were recorded. Tg-r was determined, in the region where changes in the probe distance were observed, by using linear regression technique. The effect of sample quantity, compression force, and heating rate on the determination of Tg-r was investigated. All these parameters significantly influenced the Tg-r determination (p < 0.05). The Tg-r of skim milk powder measured by this novel technique was found closely correlated to its glass transition temperature (T-g) measured by DSC.

The functions of societies and the evolution of group living: Spider societies as a test case

Many models have been advanced to suggest how different expressions of sociality have evolved and are maintained. However these models ignore the function of groups for the particular species in question. Here we present a new perspective on sociality where the function of the group takes a central role. We argue that sociality may have primarily a reproductive, protective, or foraging function, depending on whether it enhances the reproductive, protective or foraging aspect of the animal's life (sociality may serve a mixture of these functions). Different functions can potentially cause the development of the same social behaviour. By identifying which function influences a particular social behaviour we can determine how that social behaviour will change with changing conditions, and which models are most pertinent. To test our approach we examined spider sociality, which has often been seen as the poor cousin to insect sociality. By using our approach we found that the group characteristics of eusocial insects is largely governed by the reproductive function of their groups, while the group characteristics of social spiders is largely governed by the foraging function of the group. This means that models relevant to insects may not be relevant to spiders. It also explains why eusocial insects have developed a strict caste system while spider societies are more egalitarian. We also used our approach to explain the differences between different types of spider groups. For example, differences in the characteristics of colonial and kleptoparasitic groups can be explained by differences in foraging methods, while differences between colonial and cooperative spiders can be explained by the role of the reproductive function in the formation of cooperative spider groups. Although the interactions within cooperative spider colonies are largely those of a foraging society, demographic traits and colony dynamics are strongly influenced by the reproductive function. We argue that functional explanations help to understand the social structure of spider groups and therefore the evolutionary potential for speciation in social spiders.

Evaluation of random plasma cortisol and the low dose corticotropin test as indicators of adrenal secretory capacity in critically ill patients: A prospective study

It is unclear whether a random plasma cortisol measurement and the corticotropin (ACTH) test adequately reflect glucocorticoid secretory capacity in critical illness. This study aimed to determine whether these tests provide information representative of the 24 hour period. Plasma cortisol was measured hourly for 24 hours in 21 critically ill septic patients followed by a corticotropin test with 1 μ g dose administered intravenously. Serum and urine were analysed for ACTH and free cortisol respectively. Marked hourly variability in plasma cortisol was evident (coefficient of variation 8-30%) with no demonstrable circadian rhythm. The individual mean plasma cortisol concentrations ranged from 286 59 nmol/l to 796 &PLUSMN; 83 nmol/l. The 24 hour mean plasma cortisol was strongly correlated with both random plasma cortisol (r(2) 0.9, P< 0.0001) and the cortisol response to corticotropin (r(2) 0.72, P< 0.001). Only nine percent of patients increased their plasma cortisol by 250 nmol/l after corticotropin (euadrenal response). However, 35% of non-responders had spontaneous hourly rises > 250 nmol/l thus highlighting the limitations of a single point corticotropin test. Urinary free cortisol was elevated (865&PLUSMN; 937 nmol) in both corticotropin responders and non-responders suggesting elevated plasma free cortisol. No significant relationship was demonstrable between plasma cortisol and ACTH. We conclude that although random cortisol measurements and the low dose corticotropin tests reliably reflect the 24 hour mean cortisol in critical illness, they do not take into account the pulsatile nature of cortisol secretion. Consequently, there is the potential for erroneous conclusions about adrenal function based on a single measurement. We suggest that caution be exercised when drawing conclusions on the adequacy of adrenal function based on a single random plasma cortisol or the corticotropin test.

Genotoxicity of inorganic lead salts and disturbance of microtubule function

Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 μ M lead chloride and 0.05 μ M lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 μ M lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 μ M. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 μ M and reached half-maximal inhibition of motility at about 50 μ M. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels. Environ. Mal. Mutagen. 45:346-353, 2005. © 2005 Wiley-Liss, Inc.

Coupled thermal, structural and vibrational analysis of a hypersonic engine for flight test

This paper describes a relatively simple and quick method for implementing aerodynamic heating models into a finite element code for non-linear transient thermal-structural and thermal-structural-vibrational analyses of a Mach 10 generic HyShot scramjet engine. The thermal-structural-vibrational response of the engine was studied for the descent trajectory from 60 to 26 km. Aerodynamic heating fluxes, as a function of spatial position and time for varying trajectory points, were implemented in the transient heat analysis. Additionally, the combined effect of varying dynamic pressure and thermal loads with altitude was considered. This aero-thermal-structural analysis capability was used to assess the temperature distribution, engine geometry distortion and yielding of the structural material due to aerodynamic heating during the descent trajectory, and for optimising the wall thickness, nose radius of leading edge, etc. of the engine intake. A structural vibration analysis was also performed following the aero-thermal-structural analysis to determine the changes in natural frequencies of the structural vibration modes that occur at the various temperatures associated with the descent trajectory. This analysis provides a unique and relatively simple design strategy for predicting and mitigating the thermal-structural-vibrational response of hypersonic engines. (C) 2006 Elsevier SAS. All rights reserved.

The 2df SDSS LRG and QSO survey: evolution of the luminosity function of luminous red galaxies to z=0.6

We present new measurements of the luminosity function (LF) of luminous red galaxies (LRGs) from the Sloan Digital Sky Survey (SDSS) and the 2dF SDSS LRG and Quasar (2SLAQ) survey. We have carefully quantified, and corrected for, uncertainties in the K and evolutionary corrections, differences in the colour selection methods, and the effects of photometric errors, thus ensuring we are studying the same galaxy population in both surveys. Using a limited subset of 6326 SDSS LRGs (with 0.17 < z < 0.24) and 1725 2SLAQ LRGs (with 0.5 < z < 0.6), for which the matching colour selection is most reliable, we find no evidence for any additional evolution in the LRG LF, over this redshift range, beyond that expected from a simple passive evolution model. This lack of additional evolution is quantified using the comoving luminosity density of SDSS and 2SLAQ LRGs, brighter than M-0.2r - 5 log h(0.7) = - 22.5, which are 2.51 +/- 0.03 x 10(-7) L circle dot Mpc(-3) and 2.44 +/- 0.15 x 10(-7) L circle dot Mpc(-3), respectively (< 10 per cent uncertainty). We compare our LFs to the COMBO-17 data and find excellent agreement over the same redshift range. Together, these surveys show no evidence for additional evolution (beyond passive) in the LF of LRGs brighter than M-0.2r - 5 log h(0.7) = - 21 ( or brighter than similar to L-*).. We test our SDSS and 2SLAQ LFs against a simple 'dry merger' model for the evolution of massive red galaxies and find that at least half of the LRGs at z similar or equal to 0.2 must already have been well assembled (with more than half their stellar mass) by z similar or equal to 0.6. This limit is barely consistent with recent results from semi-analytical models of galaxy evolution.

Validation of the Action Research Arm Test using item response theory in patients after stroke

Objective: To validate the unidimensionality of the Action Research Arm Test (ARAT) using Mokken analysis and to examine whether scores of the ARAT can be transformed into interval scores using Rasch analysis. Subjects and methods: A total of 351 patients with stroke were recruited from 5 rehabilitation departments located in 4 regions of Taiwan. The 19-item ARAT was administered to all the subjects by a physical therapist. The data were analysed using item response theory by non-parametric Mokken analysis followed by Rasch analysis. Results: The results supported a unidimensional scale of the 19-item ARAT by Mokken analysis, with the scalability coefficient H = 0.95. Except for the item pinch ball bearing 3rd finger and thumb'', the remaining 18 items have a consistently hierarchical order along the upper extremity function's continuum. In contrast, the Rasch analysis, with a stepwise deletion of misfit items, showed that only 4 items (grasp ball'', grasp block 5 cm(3)'', grasp block 2.5 cm(3)'', and grip tube 1 cm(3)'') fit the Rasch rating scale model's expectations. Conclusion: Our findings indicated that the 19-item ARAT constituted a unidimensional construct measuring upper extremity function in stroke patients. However, the results did not support the premise that the raw sum scores of the ARAT can be transformed into interval Rasch scores. Thus, the raw sum scores of the ARAT can provide information only about order of patients on their upper extremity functional abilities, but not represent each patient's exact functioning.

Validation of a generalized transfer function to noninvasively derive central blood pressure during exercise

Exercise brachial blood pressure ( BP) predicts mortality, but because of wave reflection, central ( ascending aortic) pressure differs from brachial pressure. Exercise central BP may be clinically important, and a noninvasive means to derive it would be useful. The purpose of this study was to test the validity of a noninvasive technique to derive exercise central BP. Ascending aortic pressure waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30 patients (56 +/- 9 years; 21 men) undergoing diagnostic coronary angiography. Simultaneous recordings of the derived central pressure waveform were acquired using servocontrolled radial tonometry at rest and during supine cycling. Pulse wave analysis of the direct and derived pressure signals was performed offline (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate were increased by 20 +/- 10 mm Hg and 15 +/- 7 bpm, respectively, and central systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high correlation between invasive and noninvasive techniques with a mean difference (+/- SD) for central systolic BP of -1.3 +/- 3.2 mm Hg at rest and -4.7 +/- 3.3 mm Hg at peak exercise ( for both r=0.995; P < 0.001). Conversely, systolic BP was significantly higher peripherally than centrally at rest (155 +/- 33 versus 138 +/- 32mm Hg; mean difference, -16.3 +/- 9.4mm Hg) and during exercise (180 +/- 34 versus 164 +/- 33 mm Hg; mean difference, -15.5 +/- 10.4 mm Hg; for both P < 0.001). True myocardial afterload is not reliably estimated by peripheral systolic BP. Radial tonometry and pulse wave analysis is an accurate technique for the noninvasive determination of central BP at rest and during exercise.

A misspelt youth: Spelling and orthographic learning in university students as a function of spelling-sound consistency

Pseudowords with inconsistent vs. consistent spellings (e.g., nurch, with rhyme neighbours search, lurch & perch, vs. mish, with neighbours dish, wish) were presented with definitions for naming either twice or 6 times. In an oral spelling test, there were main and interactive effects of consistency and the number of training trials on accuracy and main effects only on response latency, with the improvement in accuracy from 2 to 6 training trials greater for the more poorly learned inconsistent items. Of most interest, the smaller effect of training on accuracy in the consistent condition was reliable; contrary to the most obvious prediction of dual route spelling models that the sublexical procedure should produce correct spellings for consistent items early in training. In a second task students wrote spellings of multisyllabic words containing unstressed indeterminate (schwa) vowels. In their errors on the schwa vowel, students showed sensitivity to the most common spelling overall but also they were influenced by differences in schwa spellings in English words as a function of the number of syllables and schwa position. These results indicate that dual route models of spelling will need to accommodate the consistency of spellings within categories defined by lexical structure variables.

Size frequency distributions of the florid prion protein aggregates in variant Creutzfeldt-Jakob disease follow a power-law function

The objective was to test the hypothesis that the size frequency distributions of the prion protein (PrP) plaques in cases of variant Creutzfeldt-Jakob disease (vCJD) follow a power-law function. The design was a retrospective neuropathological study. The patients were 11 cases of clinically and neuropathologically verified vCJD. Size distributions of the diffuse and florid-type plaques were measured in several areas of the cerebral cortex and hippocampus from each case and a power-law function fitted to each distribution. The size distributions of the florid and diffuse plaques were fitted successfully by a powerlaw function in 100% and 42% of brain areas investigated respectively. Processes of aggregation/disaggregation may be more important than surface diffusion in the pathogenesis of the florid plaques. By contrast, surface diffusion may be a more significant factor in the development of the diffuse plaques. © Springer-Verlag Italia 2006.

The effect of nutritional supplementation on visual function

The aim of this research was to determine the effect of a lutein-based nutritional supplemented on measures of visual function in normal and ARMD-affected eyes. Thirty participants were recruited to the ARMD cohort (aged between 55 and 82 years, mean ± SD: 69.2 ± 7.8) and 46 were recruited into the normal cohort (aged between 22 and 73 years, mean ± SD: 50.0 ± 15.9). Outcome measures were distance (DVA) and near (NVA) visual acuity, contrast sensitivity (CS), photostress recovery time measured with the Eger Macular Stressometer (EMS), central visual function assessed with the Macular Mapping test (MMT), and fundus photography. Reliability studies were carried out for the EMS and the MMT. A change of 14 s is required to indicate a clinically significant change in EMS time, and a change of 14 MMT points is required to indicate a clinically significant change in MMT score. Sample sizes were sufficient for the trial to have 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures in the normal cohort, and for CS in the ARMD cohort. The study demonstrated that a nutritional supplement containing 6mg lutein, 750 mg vitamin A, 250 mg vitamin C, 34 mg vitamin E, 10 mg zinc, and 0.5 mg copper had no effect on the outcome measures over nine or 18 months in normal or ARMD affected participants. The finding that nine months of antioxidant supplementation, in this case, has no significant effect on CS in ARMD-affected participants adds to the literature, and contrasts with previous RCTs, the AREDS and the LAST. This project has added to the debate about the use of nutritional supplementation prior to the onset of ARMD.

Investigation of chromatic function in the normal and abnormal eye

This study examined the use of non-standard parameters to investigate the visual field, with particular reference to the detection of glaucomatous visual field loss. Evaluation of the new perimetric strategy for threshold estimation - FASTPAC, demonstrated a reduction in the examination time of normals compared to the standard strategy. Despite an increased within-test variability the FASTPAC strategy produced a similar mean sensitivity to the standard strategy, reducing the effects of patient fatigue. The new technique of Blue-Yellow perimetry was compared to White-White perimetry for the detection of glaucomatous field loss in OHT and POAG. Using a database of normal subjects, confidence limits for normality were constructed to account for the increased between-subject variability with increase in age and eccentricity and for the greater variability of the Blue-Yellow field compared to the White-White field. Effects of individual ocular media absorption had little effect on Blue-Yellow field variability. Total and pattern probability analysis revealed five of 27 OHTs to exhibit Blue-Yellow focal abnormalities; two of these patients subsequently developed White-White loss. Twelve of the 24 POAGs revealed wider and/or deeper Blue-Yellow loss compared with the White-White field. Blue-Yellow perimetry showed good sensitivity and specificity characteristics, however, lack of perimetric experience and the presence of cataract influenced the Blue-Yellow visual field and may confound the interpretation of Blue-Yellow visual field loss. Visual field indices demonstrated a moderate relationship to the structural parameters of the optic nerve head using scanning laser tomography. No abnormalities in Blue-Yellow or Red-Green colour CS was apparent for the OHT patients. A greater vulnerability of the SWS pathway in glaucoma was demonstrated using Blue-Yellow perimetry however predicting which patients may benefit from B-Y perimetric examination is difficult. Furthermore, cataract and the extent of the field loss may limit the extent to which the integrity of the SWS channels can be selectively examined.