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The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.
Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.
We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).
These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.
Estimates of digesta passage through specific segments of the alimentary tract are a vital component of modelling approaches which attempt to quantitatively partition digestive processes in equines. This study reports results from three studies where digesta passage of Chromium (Cr) mordanted feeds was determined in the caecum of ponies.
Caecal outflow rates were determined during three in vivo apparent digestibility studies conducted using three caecally-fistulated ponies as described by Moore-Colyer et al, (1999) for studies 1 and 2; and McLean et al, (1999) for study 3. Pony basal diets consisted of unmolassed sugar beet pulp (USBP), hay cubes (HC) or a 2:1 mix of oat hulls:naked oats (OHNO) in study 1; a 1:1 mix of USBP:HC (USHC) in study 2 and either 100% HC or one of 3 diets consisting of a 1:1 HC:barley mix where the barley was either rolled (RBHC), micronised (MBHC) or extruded (EBHC) in study 3.
This paper reports the first large-sample investigation of the maltreatment-related correlates of low-income adolescents’ narratives about their childhood experiences with primary caregivers, as assessed with a modified version of the Adult Attachment Interview (AAI) and based on official reports of abuse and neglect (maltreated n = 214, nonmaltreated n = 140; M age = 16.7 years). Drawing on factor-analytic and taxometric evidence indicating that AAI narratives vary along two state of mind (i.e., dismissing and preoccupied) and two inferred childhood experience (i.e., maternal and paternal) dimensions, here we demonstrate that the experience of maltreatment, particularly when chronic, is associated with increased risk for dismissing and preoccupied states of mind and more negative inferred childhood experiences. Although such maltreatment-related associations were generally not specific to any of the four AAI dimensions, the experience of physical and/or sexual abuse was uniquely associated with preoccupied states of mind and negative inferred paternal experiences even after controlling for the other AAI dimensions. More extensive paternal perpetration of maltreatment also was uniquely related to more negative inferred paternal experiences.
Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth.
LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables.
Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%.
These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.
We present a heuristic model for the collisional evolution of material in a debris disk. This is used to consider the probability that the 2-3% brightness clump observed in the sub-mm Fomalhaut disk is caused by stochastic collisions between large planetesimals. While this simple model finds that the probability that the clump is caused by collisions is low (about 1 in 80,000), a more detailed model is required to ascertain its true likelihood.
New photometry of main-sequence debris discs has been carried out at 850 and 450/μm; the derived SEDs indicate that the dust can lie in either thin rings or radially-extended discs, as seen directly in the few nearby objects which are resolvable. All such objects are consistent with a long wavelength opacity index β of 1.0±0.2 - similar to T Tauri stars, but significantly lower than embedded objects.
Carbon films deposited by filtered cathodic vacuum arc have been used to form high quality Schottky diodes on p-Si. Energetic deposition with an applied substrate bias of -1 kV and with a substrate temperature of 100 °C has produced carbon diodes with rectification ratios of ∼ 3 × 106, saturation currents of ∼0.02 nA and ideality factors close to unity (n = 1.05). Simulations were used to estimate the effective work function and the thickness of an interfacial mixed (C/SiO2) layer from the current/voltage characteristics of the diodes.
We report on a comprehensive study of the defect structure in GaN grown on c-oriented sapphire by gas source molecular beam epitaxy and metal organic vapour phase epitaxy. Transmission electron microscopy is used to investigate the defect structures which are dominated by threading dislocations perpendicular to the sapphire surface and stacking faults. Additionally, dislocation densities are determined. For determination of dislocation densities by x-ray diffraction we employ a model that uses the linewidth of x-ray rocking curves for this purpose. Finally, Rutherford backscattering spectrometry is performed to complement the structural investigation.
Energetically-deposited carbon contacts to n-type 6H-SiC have exhibited either insulating, rectifying or ohmic electrical characteristics depending on the average energy of the depositing flux and the substrate temperature. Deposition at room temperature and at a low-medium average energy (<500 eV) has resulted in carbon with a low graphitic content and insulating electrical contacts. With higher average energy and at a moderately elevated temperature (∼100 °C), the higher graphitic content contacts were rectifying with an ideality factor, η, of ∼1.8 and barrier height of ∼0.88 eV. Oriented graphitic carbon deposited at 200 °C with biases exceeding 300 V formed ohmic contacts.
Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging.
A total of 61 youth (9–17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy.
There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n = 22) and low and decreasing (LowD; n = 39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p < 0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's < 0.001, corrected).
Patterns of function in lateral prefrontal cortical–amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.
Despite a lack of empirical evidence, many smokers and health professionals believe that tobacco smoking reduces anxiety, which may deter smoking cessation.
The study aim was to assess whether successful smoking cessation or relapse to smoking after a quit attempt are associated with changes in anxiety.
A total of 491 smokers attending National Health Service smoking cessation clinics in England were followed up 6 months after enrolment in a trial of pharmacogenetic tailoring of nicotine replacement therapy (ISRCTN14352545).
There was a points difference of 11.8 (95% CI 7.7-16.0) in anxiety score 6 months after cessation between people who relapsed to smoking and people who attained abstinence. This reflected a three-point increase in anxiety from baseline for participants who relapsed and a nine-point decrease for participants who abstained. The increase in anxiety in those who relapsed was largest for those with a current diagnosis of psychiatric disorder and whose main reason for smoking was to cope with stress. The decrease in anxiety on abstinence was larger for these groups also.
People who achieve abstinence experience a marked reduction in anxiety whereas those who fail to quit experience a modest increase in the long term. These data contradict the assumption that smoking is a stress reliever, but suggest that failure of a quit attempt may generate anxiety.
The consolidation of crystalline powders to obtain dense microstructures is typically achieved through a combination of volume and grain boundary diffusion. In situ transmission electron microscopy was utilized to study neck formation between adjacent nickel particles during the early stages of sintering. It was found that the presence of carbon during consolidation of Ni lowers the reduction temperature of nickel oxides on the particle surface and therefore has the potential to accelerate consolidation. In the absence of carbon, the surface oxides remain present during the early stage of sintering and neck formation between particles is limited by self-diffusion of nickel through the oxide layer. This study provides direct experimental evidence that corroborates related earlier hypotheses of self-cleaning on the surface of the nanoparticles that precedes neck formation and growth.
Membranes of epitaxial SiC have been used as a means of eliminating the leakage current into the Si substrate during circular transmission line model (CTLM) measurements. In the n+-3C-SiC/Si wafers, the Si substrate was etched in a patterned window with dimensions up to 10 mm × 15 mm2. An array of CTLM metal contacts was then deposited onto the upper surface of the n+-SiC membrane. The CTLM contacts on the membrane have shown an ohmic current/voltage response while electrodes located on the adjacent substrate were non-ohmic. Values of ρc were measured directly on the membranes. These results have shown a significant increase in the current flow below the metal contacts due to the presence of the Si substrate.
This paper describes the development of a nitrogen-based passivation technique for interface states near the conduction band edge [Dit(Ec)] in 4H-SiC/SiO2. These states have been observed and characterized in several laboratories for n- and p-SiC since their existence was first proposed by Schorner, et al. . The origin of these states remains a point of discussion, but there is now general agreement that these states are largely responsible for the lower channel mobilities that are reported for n-channel, inversion mode 4H-SiC MOSFETs. Over the past year, much attention has been focused on finding methods by which these states can be passivated. The nitrogen passivation process that is described herein is based on post-oxidation, high temperature anneals in nitric oxide. An NO anneal at atmospheric pressure, 1175°C and 200–400sccm for 2hr reduces the interface state density at Ec-E ≅0.1eV in n-4H-SiC by more than one order of magnitude - from > 3×1013 to approximately 2×1012cm−2eV−1. Measurements for passivated MOSFETs yield effective channel mobilities of approximately 30–35cm2/V-s and low field mobilities of around 100cm2/V-s. These mobilities are the highest yet reported for MOSFETs fabricated with thermal oxides on standard 4H-SiC and represent a significant improvement compared to the single digit mobilities commonly reported for 4H inversion mode devices. The reduction in the interface state density is associated with the passivation of carbon cluster states that have energies near the conduction band edge. However, attempts to optimize the the passivation process for both dry and wet thermal oxides do not appear to reduce Dit(Ec) below about 2×1012cm−2eV−1 (compared to approximately 1010cm−2eV−1 for passivated Si/SiO2). This may be an indication that two types of interface states exist in the upper half of the SiC band gap – one type that is amenable to passivation by nitrogen and one that is not. Following NO passivation, the average breakdown field for dry oxides on p-4H-SiC is higher than the average field for wet oxides (7.6MV/cm compared to 7.1MV/cm at room temperature). However, both breakdown fields are lower than the average value of 8.2MV/cm measured for wet oxide layers that were not passivated. The lower breakdown fields can be attributed to donor-like states that appear near the valence band edge during passivation.
Strain relaxed Si1−xGex buffer layers are of great importance as virtual substrates for Si1−xGex/Si quantum well structures and devices. We apply He+ ion implantation and subsequent annealing on pseudomorphic, MBE-grown Si1−xGex/Si(100) heterostructures with an implantation depth of about 100 nm below the Si1−xGex/Si interface. A narrow defect band is generated inducing the formation of strain relieving misfit dislocations during subsequent thermal annealing. Efficient strain relaxation was demonstrated for Si1−xGex layers with Ge fractions up to 30 at. %. The variation of the implantation dose and the annealing conditions changes the dislocation configuration and the He bubble structure. At a dose of 2×1016 cm−2 a high degree of relaxation is accompanied by a low density of threading dislocations of about 107 cm−2 for a Ge content of 30%. An additional increase of the Ge content can be achieved by annealing in oxygen. The oxidation of Si1−xGex leads to the formation of SiO2 while the Ge atoms are rejected from the oxide leading to a pile-up of Ge below the oxidation front. The heterostructures were analyzed using X-ray diffraction, Rutherford backscattering/channeling spectrometry and transmission electron microscopy.