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Prolactin (PRL) data from adolescents treated with olanzapine are presented.
Data from 454 adolescents (13-18, mean=15.9 yrs) with schizophrenia or bipolar mania were pooled from 4 olanzapine (2.5-20.0mg/day) studies (4-32 weeks; 2 double-blind, placebo-controlled studies [combined for acute phase endpoint PRL levels] with open-label extensions; 2 open-label studies). Age- and sex-specific Covance reference ranges defined normal PRL; categorical increases were based on multiples of the upper limit of normal (ULN). Baseline-to-endpoint PRL changes in adolescents were compared with data pooled from 84 olanzapine clinical trials in adults with schizophrenia or bipolar disorder.
Olanzapine-treated adolescents had mean PRL increases at both the acute (11.4μg/L) and open-label endpoints (4.7μg/L). Of those patients with normal PRL levels at baseline (N=311), high PRL occurred in 54.7% at anytime; 32.2% at endpoint. The percentage of patients in which PRL levels shifted from normal-to-abnormal was smaller at endpoint than at anytime during treatment; 26.7% shifted to a higher category. Among patients with normal baseline PRL, 32.7% remained <=1X ULN; 32.3% increased to 1¬<=2X; 6.0%, >2-<=3X; and 1.2%, >3X at anytime; 4.6% had at >=1 potentially PRL-related adverse event. Adolescents had significantly higher mean changes at endpoint (p=.004), and a greater incidence of high PRL levels at anytime during olanzapine treatment (p<.001) versus adults.
Incidence of high PRL was significantly higher, and mean increases in PRL were significantly greater in adolescents versus adults. Mean increases and high PRL incidence were lower at the open-label compared with the acute phase endpoint.
The changes in metabolic parameters in olanzapine-treated adolescents were examined.
Data from 454 adolescents (13–18, mean=15.9 years) with schizophrenia or bipolar I disorder were pooled from 4 olanzapine (2.5–20.0mg/day) studies (4–32 weeks). Changes in metabolic parameters in adolescents were compared with those of olanzapine-treated adults (pooled from 84 clinical trials); changes in weight and BMI were compared with US age- and sex-adjusted standardized growth curves.
Olanzapine-treated adolescents had significant increases from baseline-to-endpoint in fasting glucose (p=.021); total cholesterol, LDL, and triglycerides (p<.001); and significant decreases in HDL (p<.001). Significantly more adolescents gained >=7% of their baseline weight versus adults (65.1% vs. 35.6%, p<.001); mean change from baseline-to-endpoint in weight was significantly greater in adolescents (7.0 vs. 3.3kg, p<.001). Adolescents had significantly lower mean changes from baseline-to-endpoint in fasting glucose (0.3 vs. 0.1mmol/L, p=.002) and triglycerides (0.3 vs. 0.2mmol/L, p=.007) versus adults. Significantly more adults experienced treatment-emergent normal-to-high changes at anytime in fasting glucose (4.8% vs. 1.2%, p=.033), total cholesterol (6.9% vs. 1.1%, p=.001), LDL (5.8% vs. 1.5%, p=.014), and triglycerides (25.7% vs. 17.4%, p=.030). Compared with standardized growth curves, olanzapine-treated adolescents had greater increases from baseline-to-endpoint in weight (1.0 vs. 7.1kg, p<.001), height (0.5 vs. 0.7cm, p<.001), and BMI (0.2 vs. 2.2kg/m2, p<.001).
Olanzapine-treated adolescents may gain significantly more weight compared with adults, but may have smaller changes in other metabolic parameters. Clinicians may want to consider both efficacy and changes in metabolic parameters when selecting treatment options for individual adolescent patients.
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.
Historically, alloy development with better radiation performance has been focused on traditional alloys with one or two principal element(s) and minor alloying elements, where enhanced radiation resistance depends on microstructural or nanoscale features to mitigate displacement damage. In sharp contrast to traditional alloys, recent advances of single-phase concentrated solid solution alloys (SP-CSAs) have opened up new frontiers in materials research. In these alloys, a random arrangement of multiple elemental species on a crystalline lattice results in disordered local chemical environments and unique site-to-site lattice distortions. Based on closely integrated computational and experimental studies using a novel set of SP-CSAs in a face-centered cubic structure, we have explicitly demonstrated that increasing chemical disorder can lead to a substantial reduction in electron mean free paths, as well as electrical and thermal conductivity, which results in slower heat dissipation in SP-CSAs. The chemical disorder also has a significant impact on defect evolution under ion irradiation. Considerable improvement in radiation resistance is observed with increasing chemical disorder at electronic and atomic levels. The insights into defect dynamics may provide a basis for understanding elemental effects on evolution of radiation damage in irradiated materials and may inspire new design principles of radiation-tolerant structural alloys for advanced energy systems.
Observations of the red giants in NGC 1866 in the Large Magellanic Cloud, made by Arp and Thackeray provide a strict test for core helium burning models of about 5M⊙. The main observational features to be reproduced theoretically are the luminosity of the red giants, the range in effective temperature that they occupy and the ratio of the number of giants near the blue end of this range to the number at the bottom of the red giant branch. Meyer-Hofmeister attempted a theoretical fit to these observations using the initial (X, Y, Z) composition (0.602, 0.354, 0.044) and assuming the stars to have formed uniformly over a period of 1.5 × 107 years about a mean age of 5.75 × 107 years. Although she was able to fit the luminosity and effective temperature spread of the red giants, her theory predicted far too many stars at the bottom of the red giant branch relative to the number of bluer giants.
The existence of red supergiants such as those in the clusters h and χ Persei has puzzled stellar evolution theoreticians for some time. Suggested explanations for them have included stars in a stage of gravitational contraction to the main sequence, or between nuclear burnings, core helium burning stars, and stars burning carbon or oxygen in the core, but it is now generally accepted that most red supergiants are core helium burning stars.
We present preliminary results from a programme designed to produce deep images of radio source fields drawn from the Parkes 2700 MHz and Molongolo 408 MHz catalogues using the charge-coupled-device (CCD) camera system built at the Institute of Astronomy, Cambridge. The programme is directed at a search both for faint extensions and nebulosity around radio QSOs and BL Lac objects and for faint objects in otherwise empty radio source fields; a detailed examination of the morphology of selected radio galaxies is also included.
Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R0 of 1·71–3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.
Background: Few data are available on the neuropsychological, behavioural, or structural brain imaging outcomes in adolescents who underwent corrective surgery in infancy for tetralogy of Fallot. Methods: In this single-centre cross-sectional study, we enrolled 91 adolescents (13–16 years old) with tetralogy of Fallot and 87 referent subjects. Assessments included tests of academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition, as well as brain magnetic resonance imaging. Results: Genetic abnormalities or syndromes were present in 25% of tetralogy of Fallot patients, who had markedly greater neuropsychological morbidities than did patients without a syndrome. However, even patients without a syndrome performed significantly worse than the referent group or population norms in all of the neuropsychological domains assessed. In multivariable regression in those without a genetic/phenotypic syndrome, the strongest predictors of adverse late neurodevelopmental outcomes included a greater number of complications at the first operation, more total surgical complications across all operations, and occurrence of post-operative seizures. The presence of at least one abnormality on structural magnetic resonance imaging was more frequent in tetralogy of Fallot patients than the referent group (42% versus 8%). Conclusions: Adolescents with tetralogy of Fallot are at increased neurodevelopmental risk and would benefit from ongoing surveillance and educational supports even after childhood.
A microcompressor is a precision mechanical device that flattens and immobilizes living cells and small organisms for optical microscopy, allowing enhanced visualization of sub-cellular structures and organelles. We have developed an easily fabricated device, which can be equipped with microfluidics, permitting the addition of media or chemicals during observation. This device can be used on both upright and inverted microscopes. The apparatus permits micrometer precision flattening for nondestructive immobilization of specimens as small as a bacterium, while also accommodating larger specimens, such as Caenorhabditis elegans, for long-term observations. The compressor mount is removable and allows easy specimen addition and recovery for later observation. Several customized specimen beds can be incorporated into the base. To demonstrate the capabilities of the device, we have imaged numerous cellular events in several protozoan species, in yeast cells, and in Drosophila melanogaster embryos. We have been able to document previously unreported events, and also perform photobleaching experiments, in conjugating Tetrahymena thermophila.
New angular diameter determinations for the bright southern F8 supergiant δ CMa enable the bolometric emergent flux and effective temperature of the star to be determined with improved accuracy. The spectral flux distribution and bolometric flux have been determined from published photometry and spectrophotometry and combined with the angular diameter to derive the bolometric emergent flux ℱ = (6.50 ± 0.24) × 107 Wm−2 and the effective temperature Teff = 5818 ± 53 K. The new value for the effective temperature is compared with previous interferometric and infrared flux method determinations. The accuracy of the effective temperature is now limited by the uncertainty in the bolometric flux rather than by the uncertainty in the angular diameter.
A new beam-combination and detection system has been installed in the Sydney University Stellar Interferometer working at the red end of the visual spectrum (λλ 500–950 nm) to complement the existing blue-sensitive system (λλ 430–520 nm) and to provide an increase in sensitivity. Dichroic beam-splitters have been introduced to allow simultaneous observations with both spectral systems, albeit with some restriction on the spectral range of the longer wavelength system (λλ 550–760 nm). The blue system has been upgraded to allow remote selection of wavelength and spectral bandpass, and to enable simultaneous operation with the red system with the latter providing fringe-envelope tracking. The new system and upgrades are described and examples of commissioning tests presented. As an illustration of the improvement in performance the measurement of the angular diameter of the southern F supergiant δ CMa is described and compared with previous determinations.
We describe a newly refined procedure for making optical identifications of radio sources in Abell cluster fields observed with the Molonglo Observatory Synthesis Telescope (MOST). The method is based on past experience but uses a range of new tools to improve the reliability and production rate of identification lists. The COSMOS/UKST Southern Sky Object Catalogue was used to make preliminary identifications which were then inspected visually with the assistance of computer generated overlays of the MOST images and the Digitized Sky Survey (DSS). The overlaid images were essential for securing identifications for the extended sources prevalent among nearby clusters.
We find 21±1·5% of the radio sources are identified with galaxies and 4·6±0·7% with QSO candidates in a sample of 927 radio sources in 27 cluster fields. We make a preliminary attempt to separate cluster radio galaxies from interlopers on the basis of absolute magnitudes. A strong concentration of radio galaxies was found at projected distances less than 100 kpc from the cluster centres and a weaker concentration for projected distances of 100–500 kpc.
The Sydney University Stellar Interferometer (SUSI) has been used to make a new determination of the angular diameter of Sirius A. The observations were made at an effective wavelength of 694.1 nm and the new value for the limb-darkened angular diameter is 6.048 ± 0.040 mas (± 0.66%). This new result is compared with previous measurements and is found to be in excellent agreement with a conventionally calibrated measurement made with the European Southern Observatory's Very Large Telescope Interferometer (VLTI) at 2.176 μm (but not with a second globally calibrated VLTI measurement). A weighted mean of the SUSI and first VLTI results gives the limb-darkened angular diameter of Sirius A as 6.041 ± 0.017 mas (± 0.28%). Combination with the Hipparcos parallax gives the radius equal to 1.713 ± 0.009 R⊙. The bolometric flux has been determined from published photometry and spectrophotometry and, combined with the angular diameter, yields the emergent flux at the stellar surface equal to (5.32 ± 0.14) × 108 W m−2 and the effective temperature equal to 9845 ± 64 K. The luminosity is 24.7 ± 0.7 L⊙.
An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42–66); age-specific adjusted VE was 87% (95% CI 45–97) in <5-year-olds and 84% (95% CI 27–97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI −6 to 51) overall and 72% (95% CI 15–91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42–68) and in 5- to 14-year-olds 75% (95% CI 32–91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.
A single nucleotide polymorphism rs12807809 located upstream of the neurogranin (NRGN) gene has been identified as a risk variant for schizophrenia in recent genome-wide association studies. To date, there has been little investigation of the endophenotypic consequences of this variant, and our own investigations have suggested that the effects of this gene are not apparent at the level of cognitive function in patients or controls. Because the impact of risk variants may be more apparent at the level of brain, the aim of this investigation was to delineate whether NRGN genotype predicted variability in brain structure and/or function. Healthy individuals participated in structural (N = 140) and/or functional (N = 36) magnetic resonance imaging (s/fMRI). Voxel-based morphometry was used to compare gray and white matter volumes between carriers of the non-risk C allele (i.e., CC/CT) and those who were homozygous for the risk T allele. Functional imaging data were acquired during the performance of a spatial working memory task, and were also analyzed with respect to the difference between C carriers and T homozygotes. There was no effect of the NRGN variant rs12807809 on behavioral performance or brain structure. However, there was a main effect of genotype on brain activity during performance of the working memory task, such that while C carriers exhibited a load-independent decrease in left superior frontal gyrus/BA10, TT individuals failed to show a similar decrease in activity. The failure to disengage this ventromedial prefrontal region, despite preserved performance, may be indicative of a reduction in processing efficiency in healthy TT carriers. Although it remains to be established whether this holds true in larger samples and in patient cohorts, if valid, this suggests a potential mechanism by which NRGN variability might contribute to schizophrenia risk.
We present the first near millennium-length, annually resolved stable isotope record from bristlecone pines (Pinus longaeva, D.K Bailey). The carbon isotope ratios from the cellulose of seven trees from the White Mountains of California, corrected for anthropogenic changes in atmospheric chemistry, are used to reconstruct growing season (June through August) precipitation back to AD 1085. Extremely negative isotope results are strongly correlated with proposed severest El Niño events over the last 500 yr, and similar values in the first half of the millennium are used to reconstruct a further 13 strong El Niño events, concentrated in the 12th Century and the mid 13th and 14th Centuries. Ring-width chronologies from adjacent sites in the White Mountains demonstrate a high degree of decadal covariance with the δ13C series, although there are several periods of notable divergence.