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Most basic science research has focused on overt stroke caused by blockage of major blood vessels. Less attention has been paid to small vessel disease giving rise to covert stroke that often leads to vascular cognitive impairment (VCI). One reason for this may be the relative lack of relevant animal models. This talk will describe a model of VCI induced in middle-aged Sprague-Dawley rats exposed to a diet high in saturated fats, salt and refined sugar (HFSS). In Experiment 1, rats fed HFSS and subjected to a small mediodorsal (MD) thalamic stroke with or without concomitant cerebral hypoperfusion experienced significant executive dysfunction. In Experiment 2, dietary influences on functional, physiological and anatomical parameters were assessed. We found significant hypertension, blockage of brain microvessels (2-photon microscopy) and white matter atrophy in HFSS diet animals. As in Experiment 1, profound, specific set-shifting executive dysfunction was noted following both small MD infarcts (0.332 mm3) and the HFSS diet. In summary, these data describe a middle-aged animal model of VCI that includes clinically-relevant metabolic disturbances and small vessel disease and as such may be helpful in developing new cognitive therapies.
Generalized anxiety disorder (GAD) and panic disorder (PD) differ in their biology and co-morbidities. We hypothesized that GAD but not PD symptoms at the age of 15 years are associated with depression diagnosis at 18 years.
Using longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort we examined relationships of GAD and PD symptoms (measured by the Development and Well-Being Assessment) at 15 years with depression at 18 years (by the Clinical Interview Schedule – Revised) using logistic regression. We excluded adolescents already depressed at 15 years and adjusted for social class, maternal education, birth order, gender, alcohol intake and smoking. We repeated these analyses following multiple imputation for missing data.
In the sample with complete data (n = 2835), high and moderate GAD symptoms in adolescents not depressed at 15 years were associated with increased risk of depression at 18 years both in unadjusted analyses and adjusting for PD symptoms at 15 years and the above potential confounders. The adjusted odds ratio (OR) for depression at 18 years in adolescents with high relative to low GAD scores was 5.2 [95% confidence interval (CI) 3.0–9.1, overall p < 0.0001]. There were no associations between PD symptoms and depression at 18 years in any model (high relative to low PD scores, adjusted OR = 1.3, 95% CI 0.3–4.8, overall p = 0.737). Missing data imputation strengthened the relationship of GAD symptoms with depression (high relative to low GAD scores, OR = 6.2, 95% CI 3.9–9.9) but those for PD became weaker.
Symptoms of GAD but not PD at 15 years are associated with depression at 18 years. Clinicians should be aware that adolescents with GAD symptoms may develop depression.
Iodine deficiency has recently been found in UK young and pregnant women, which is of concern given the importance of adequate iodine intake in pregnancy for fetal brain development. The WHO recommends that iodine deficiency in a population should be corrected through salt iodisation but there is a lack of UK data on iodised-salt availability, a situation that the present study aimed to address.
Availability of iodised salt for household use was determined by a shelf survey in five supermarket chains in each of sixteen UK areas (in Southern England, Wales and Northern Ireland) encompassing a total of seventy-seven supermarkets. All branches of a sixth supermarket chain that had 2·3 % of the market share sold exclusively iodised salt. Weighted iodised-salt availability was calculated taking the market share of supermarkets into account.
Iodised salt was available in thirty-two of the seventy-seven supermarkets (41·6 %). After accounting for market share and including all six UK supermarket chains, the weighted availability of iodised salt was 21·5 %. The iodine concentration of the major UK brand of iodised salt is low, at 11·5 mg/kg.
In contrast to other countries, iodised household table salt is unlikely to contribute meaningful amounts to UK iodine intake as (i) availability is low, (ii) table salt is only a small percentage of total UK salt intake and (iii) UK public-health campaigns have encouraged reduced salt consumption. As iodine intake in the UK is dependent entirely on food choices, regular monitoring of iodine status is essential.
In this paper we shall look at a technique, known as impurity free vacancy diffusion (IFVD) for selectively altering the optoelectronic response of quantum well material after growth with a view to monolithic device integration. We will discuss the mechanism, practical considerations and some possible applications.
Iodine is required for adequate thyroid hormone production, which is essential for brain development, particularly in the first trimester of pregnancy. Milk is the principal source of iodine in UK diets, and while small studies in Europe have shown organic milk to have a lower iodine concentration than conventional milk, no such study has been conducted in Britain. In view of the increasing popularity of organic milk in the UK, we aimed to compare the iodine concentration of retail organic and conventional milk and to evaluate regional influences in iodine levels. Samples of organic milk (n 92) and conventional milk (n 80), purchased from retail outlets in sixteen areas of the UK (southern England, Wales and Northern Ireland), were analysed for iodine using inductively coupled plasma MS. The region of origin of the milk was determined from information on the label. Organic milk was 42·1 % lower in iodine content than conventional milk (median iodine concentration 144·5 v. 249·5 ng/g; P < 0·001). There was no difference in the iodine concentration of either conventional or organic milk by area of purchase. However, a difference was seen in iodine concentration of organic milk by region of origin (P < 0·001). The lower iodine concentration of organic milk has public-health implications, particularly in view of emerging evidence of iodine deficiency in UK population sub-groups, including pregnant women. Individuals who choose organic milk should be aware that their iodine intake may be compromised and should ensure adequate iodine intake from alternative sources.
An essentially impurity free, direct write and potentially high spatial resolution quantum well intermixing technique using pulsed laser irradiation is reported. This technique uses a Q-switched Nd:YAG laser emitting at 1.06 μm with a pulse length of ∼20 ns and repetition rate of 10 Hz. The typical energy densities used for both Gain As/Gain AsP and GaAs/AlGaAs structures were ∼ 5 mJ mm−2. Multiphoton interactions with carriers lead to phonon emission, the phonons interact with the lattice thus generating point defects which diffuse during a subsequent annealing stage in a rapid thermal annealer and cause intermixing. Photoluminescence measurements have demonstrated that the spatial resolution of the process is better than the resolution of the PL measurement (ie better than 25 μm) and the technique has been used to write directly a grating of period 1.25 μm into a GalnAs/GalnAsP quantum well structure. This was achieved using a grating of period 2.5 μm etched into the surface of the substrate; when illuminated by the Q-switched pulses this grating generated a volume hologram of point defects within the sample at half the etched period. A clear dip in the transmission spectrum of the waveguide which had been processed in this way was observed at 1.525 μm. Differential bandgap shifts of up to 40 meV have been observed in GaAs/AlGaAs double quantum well samples. 3 μm wide ridge waveguide lasers were fabricated from the intermixed and control samples. The threshold currents of the intermixed and the control lasers were comparable. The slope efficiency of the intermixed lasers showed insignificant changes when compared to the as-grown lasers.
In this study we report discovery of a new type of water bell. This is formed by impinging a vertical liquid jet on to the underside of a large horizontal flat plate. After impact, the liquid spreads radially along the plate before falling at an abrupt unspecified radius. This falling liquid may then coalesce to form a curtain which encloses a volume of air. When the flow rate of the impinging jet is altered from the value at initial formation, a pronounced hysteretic effect in the water bell shape can be observed. We present detailed observations of these new phenomena, including the size and nature of the flow underneath the plate and the shape of the liquid curtain. These observations are interpreted theoretically in a companion paper (Part 2, Button et al. vol. 649, 2010, pp. 45–68).
In a companion paper (Part 1, Jameson et al. J. Fluid Mech. vol. 649, 2010, 19–43), the discovery of a new type of water bell was reported. When a vertical liquid jet impacts on the underside of a large horizontal plate, the resulting thin film spreads radially along the plate to an unspecified abrupt departure point, from whence it falls away from the plate of its own accord. The departure radius of the fluid from the plate is seen to depend strongly on the volumetric flow rate. The falling liquid may then coalesce to form a water bell. Here we present a theoretical analysis and explanation of this phenomenon. A force balance determining the maximum radial extension of the thin film flow along the plate is considered as a mechanism for fluid departure from the plate, for which an analytical model is developed. This model gives good predictions of the measured radius of departure. When a water bell has been formed, and the flow rate is altered, many interesting shapes are produced that depend on the shapes at previous flow rates. We discuss the origin of this hysteresis, and also present a leading order theory for the bell shape under a regime of changing flow rate. The models are compared with experimental results spanning two orders of magnitude in viscosity.
To investigate the extent to which three putative ‘environmental’ risk factors, maternal punitive discipline (MPD), paternal punitive discipline (PPD) and negative life events (NLEs), share genetic influences with, and moderate the heritability of, externalizing behavior.
The sample consisted of 2647 participants, aged 12–19 years, from the G1219 and G1219Twins longitudinal studies. Externalizing behavior was measured using the Youth Self-Report, MPD, PPD and exposure to NLEs were assessed using the Negative Sanctions Scale and the Life Event Scale for Adolescents respectively.
Genetic influences overlapped for externalizing behavior and each ‘environmental’ risk, indicating gene–environment correlation. When controlling for the gene–environment correlation, genetic variance decreased, and both shared and non-shared environmental influences increased, as a function of MPD. Genetic variance increased as a function of PPD, and for NLEs the only interaction effect was on the level of non-shared environment influence unique to externalizing behavior.
The magnitude of the influence of genetic risk on externalizing behavior is contextually dependent, even after controlling for gene–environment correlation.
Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview — Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.
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