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Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
Methods
The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
Results
Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
Conclusions
The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
Child maltreatment is a major risk factor for psychopathology, including reactive attachment disorder (RAD).
Aims
To examine whether neural activity during reward processing was altered in children and adolescents with RAD.
Method
Sixteen children and adolescents with RAD and 20 typically developing (TD) individuals performed tasks with high and low monetary rewards while undergoing functional magnetic resonance imaging.
Results
Significantly reduced activity in the caudate and nucleus accumbens was observed during the high monetary reward condition in the RAD group compared with the TD group (P=0.015, family-wise error-corrected cluster level). Significant negative correlations between bilateral striatal activity and avoidant attachment were observed in the RAD and TD groups.
Conclusions
Striatal neural reward activity in the RAD group was markedly decreased. The present results suggest that dopaminergic dysfunction occurs in the striatum of children and adolescents with RAD, leading towards potential future risks for psychopathology.
To investigate the therapeutic effects of antioxidants on the clinical and biochemical outcome of patients with nasal polyposis.
Methods:
Thirty-four patients with nasal polyposis were divided into two groups receiving either intranasal steroid or intranasal steroid plus per-oral vitamins A, C and E and selenium. Paranasal sinus computed tomography, endoscopy, and polyp tissue and serum sampling were conducted pre- and post-therapy. Serum levels of malondialdehyde, superoxide dismutase, nitrite and myeloperoxidase and tissue levels of malondialdehyde and superoxide dismutase were measured. Group results were compared using the Mann–Whitney U test and Wilcoxon signed-rank test.
Results:
Both groups had significantly lower tissue parameters, computed tomography scores and serum malondialdehyde levels, comparing pre- versus post-treatment results. Post-treatment, the steroid plus antioxidant group had significantly lower tissue malondialdehyde levels and a greater fall in tissue and serum malondialdehyde, compared with the steroid group.
Conclusion:
Serum and tissue levels of malondialdehyde (an oxidative marker) were significantly decreased by adding antioxidants to standard therapy. This is the first report of the positive effects of adding antioxidants to steroid therapy for nasal polyposis.
Low-cost OEM GPS receivers with the capability of tracking the carrier phase are now used for many applications in the navigation and tracking arena. These receivers provide flexibility in applying carrier smoothing algorithms to improve the pseudorange positioning accuracy and even perform carrier-phase differential positioning. In this study, the performance of a low-cost single-frequency OEM GPS receiver for high-accuracy kinematic positioning in marine applications is investigated. As a first step, a set of zero baseline tests were carried out to evaluate the performance of the GPS receivers. In the second stage, a kinematic test was conducted at the Halic (Golden Horn), Istanbul. The results show that kinematic positioning with centimetre level accuracy can be achieved by the low-cost OEM GPS receiver in differential mode, suggesting its use in a variety of kinematic applications. The use of such a system could considerably reduce the cost of the GPS receiver and the total project costs of many applications.
The inhibitory influence of cyanuric acid on the virucidal effect of chlorine was studied. The time required for 99·9% inactivation of ten enteroviruses and two adenoviruses by 0·5 mg/l free available chlorine at pH 7·0 and 25○C was prolonged approximately 4·8–28·8 times by the addition of 30 mg/l cyanuric acid. Comparative inactivation of poliovirus 1 by free available chlorine with or without cyanuric acid revealed the following. The inactivation rate by 1·5 mg/l free available chlorine with 30 mg/l cyanuric acid or by 0·5 mg/l free available chlorine with 1 mg/1 cyanuric acid was slower than by 0·5 mg/1 free available chlorine alone. Temperature and pH did not affect the inhibitory influence of cyanuric acid on the disinfectant action of chlorine. In the swimming-pool and tap water, cyanuric acid delayed the virucidal effect of chlorine as much as in the ‚clean’ condition of chlorine-buffered distilled water. The available chlorine value should be increased to 1·5 mg/l when cyanuric acid is used in swimming-pool water.
X-linked retinoschisis (XLRS) is a common form of inherited macular degeneration caused by mutations in the RS1 gene. Whereas the role of RS1 has been implicated in the synaptic structure as well as layer organization in the retina, the pathological effect of a defective RS1 gene on the synaptic interaction between photoreceptor cells and second-order neurons has not been thoroughly investigated. In this study, we perform a detailed characterization of the retinal synaptic phenotypes caused by a splice site mutation in the murine RS1 homolog (Rs1htmgc1). Electron microscopic analysis showed that presynaptic terminals of photoreceptor cells contain a lower areal density of synaptic vesicles in the Rs1htmgc1 retina. Examination of the synaptic interactions in the outer plexiform layer also revealed ectopic localization of photoreceptor cell presynaptic markers and elongation of neurites from postsynaptic neurons (bipolar and horizontal cells), which are observed in other mouse models with defective photoreceptor cell molecules. Consistent with these synaptic abnormalities, ERG analysis of young Rs1htmgc1 mice revealed attenuation of the b-wave with preservation of the a-wave. These results demonstrate that RS1H has functional significance in the morphology and function of the synapse between photoreceptors and second-order neurons. A developmental study from postnatal day (P) 15 through P19 showed that synaptic interactions form normally, and structural abnormalities occur after completion of synaptic formation suggesting that RS1H is important for the maintenance of this synaptic interaction. Thus, Rs1htmgc1 mice may serve as a new genetic model for human XLRS and other synaptic disorders.
Recent progress in in situ observation of solid–liquid interfaces by means of transmission electron microscopy, carried out by the Nagoya group, was reviewed. The results obtained on pure materials are discussed based on Jackson's theory. The structure of the solid–liquid interfaces of eutectic alloys was also observed. The in situ observation technique of solid–liquid interface is applied to industrially important reactions which include liquid phases.
In this study, the microstructural change of the surface of Si single crystal (Si(100)) after the scratching tests under very small loading forces was investigated. At first, line-scratching tests and scanning-scratching tests were carried out using an atomic force/friction force microscope (AFM/FFM). Next, cross-sectional TEM observations of the wear marks which were generated by the scratching tests were carried out. As a result of the TEM observations after the line-scratching tests, it was found that dislocations were observed in the area of less than 100nm thickness from the surface of the wear marks which were formed under the loading forces of more than 5μN. In the case of the loading forces of more than 20μN, an amorphous region was also observed just under the wear marks. As a result of the TEM observations after the scanning-scratching tests, it was found that the introduction of dislocations took place and no amorphous region appeared. It was also found that the several atomic layers at the top surface of the wear marks shifted in parallel to (100).
The accuracy that can be achieved by a single GPS receiver in stand-alone mode is around 10 metres with SA switched off; this is not adequate for most hydrographic studies. This study aims to improve this level of accuracy using a single geodetic receiver in stand-alone mode by applying a phase smoothing algorithm. The algorithm described in this study requires that the measurements be started from a known point for initialisation. The test site selected for the study is Halic bay, Istanbul. After GPS data were collected on a geodetic point for initialisation, the receiver was moved to a hydrographic vessel and trial measurements were performed along several survey profiles. The position of the vessel was calculated at every epoch using the carrier phase smoothing algorithm. In order to analyse the accuracy of the results, a second receiver collected data on another known point on the seashore during the whole session. The position of the vessel was accurately determined using a kinematic positioning method considering the data collected by both receivers. The results produced show that an accuracy of less than a metre can be achieved using the approach considered in this study.
Microtribology of Silicon single crystals is one of the important factors for the practical use of MEMS. In this study, the effect of crystal orientation on microwear of Silicon single crystal and the wear structure were mainly investigated. Microfriction experiments using atomic force / friction force microscope (AFM / FFM) were carried out to investigate the effect of crystal orientation on the microwear depth of Silicon single crystals. In these experiments, the scanning-scratching directions of a tip of AFM / FFM were <100> and <110> on Si(100) surface and <112> on Si(111) surface. As a result, it was found that the depth of the wear marks generated on Silicon surfaces increased in the following order: <112>, <100>, <100>. Cross-sectional TEM observations of the microwear marks were carried out. As a result, it was found that the small dislocation loops were generated in the surface region at the first stage of the microwear, and the size and the number of dislocations increased with the progress of the microwear.
In 1996, three adenovirus type 7 (Ad7) strains were isolated from children with fever and upper respiratory diseases in Japan. Restriction endonucleases (REs) analysis and PCR amplification of the E3 7·7 kDa ORF revealed that these strains were genotype Ad7h and closely related to an Argentine Ad7h strain, which has been reported to be highly virulent and so far predominant only in South America. These strains showed weak cross-neutralizing activity and specific haemagglutination-inhibition activity to Ad3 antiserum. The present findings suggest that Ad7h in South America has spread to other parts of the world. Since the seroprevalence to Ad7 in the current Japanese population is very low due to the absence of Ad7 circulation in Japan for decades, Ad7 outbreak as a typical case of re-emerging infectious diseases is a cause for serious concern.
Melting and solidification of metallic materials have been observed directly using an in-situ heating experiment in an electron microscope. In pure Al melting initiates at the surface, while in a eutectic alloy melting initiates preferentially at eutectic interfaces and grain boundaries. The atomic structure of a solidliquid interface was identified by comparing an experimental image with computed ones.
Defect structure beneath and near Vickers indentations made with loads of 10, 25 and 50g in Si has been studied in detail by TEM. Both plan-view and cross-sectional observations have been made. Beneath the 10 and 25g indentations an amorphous phase is formed, but beneath the 50g indentation no amorphous phase is formed.
Mode I cracks introduced in Si at the ductile-brittle transition temperature (DBTT) have been examined extensively using transmission electron microscopy. Cross-sectional as well as plane-view specimens suitable for the observation were prepared using a focused ion beam technique. Many small dislocation loops nucleate at the fracture surface of a mode I crack during the propagation at DBTT.
Annealing effects on Al-Nd (0.19 – 1.82 at. %) thin films deposited on a glass substrate have been investigated. It is found that the resistivity of an Al-Nd-alloy thin film decreases significantly after annealing at 300 °C or higher temperatures. Using cross-sectional transmission electron microscopy (X-TEM), we have observed segregation of Al-Nd inter-metallic precipitates and pure-Al grains during the annealing. The decrease of the resistivity can be attributed to the segregation. Segregation has been also detected from the increase of diffracted X-ray intensities corresponding to Al-Nd inter-metallic compounds in X-ray diffraction (XRD) analysis. Atomic force microscopy (AFM) observation has revealed that the optimum content ratio of Nd in Al-Nd alloys used as interconnect materials for thin-film-transistor liquid crystal display (TFT/LCD) applications is around 0.97 atomic %.
A rapid and precise sample preparation method using focused ion beam (FIB) etching was developed for cross-sectional transmission electron microscopy (X-TEM) analysis of a thin-film transistor (TFT) fabricated on a glass substrate. Gallium (Ga) ions accelerated at 30 kV and at various incident beam angles were applied during FIB etching to create a uniform thin wall. We successfully prepared X-TEM specimens of long and fragile aluminum (Al) whiskers formed on thin Al films in TFT metallization, where a strong charge is built up during FIB etching. The effect of ion-beam-assisted tungsten deposition prior to FIB etching is discussed. A whisker having a length not exceeding approximately 10 #x00B5;m can be successfully etched to a thickness of 200 nm while keeping its original shape. The performance of this technique is demonstrated in applications to etching at other fragile locations related to TFTs.
The recent attention paid to stress migration of aluminum (Al) electrodes in thin-film transistor liquid crystal display (TFT-LCD) applications indicates that wiring materials with low electrical resistivities are of considerable interest for their potential use in higher-resolution displays. In this paper, we firstly describe how as-grown Al whiskers on Al electrodes fabricated on a LCD-grade glass substrate can be characterized by means of a high-voltage transmission electron microscope (HV-TEM) operated at 1 MV. The whiskers ranging from 300 to 400 nm in diameter are sufficient to be transparent to high-voltage electrons. This allows detailed observation of whisker characteristics such as its morphology and crystallography. In most cases, the as-grown Al whiskers in our study had straight rod shapes, and could be regarded as single crystals. Secondly, we report on the in-situ fabrication and observation of Al whiskers at elevated temperature with the HV-TEM. Since relatively thick TEM samples (up to about 1 mm) can be set on a sample holder in the HV-TEM, various growth stages of Al whiskers can be investigated under various heating conditions. Finally, we demonstrate a TEM sample preparation method for the cross-section of an individual Al whisker, using focused ion beam (FIB) etching. This technique makes it possible to reduce the thickness of an Al whisker close to the root. Both bright- and dark-field TEM images provide nanostructural information on the whisker/Al thin-film interface.
The relation between the nanostructure of pure Al and Al-0.2 wt.% Cu thin films on glass substrates and anti-stress migration properties were investigated. These films were deposited on liquid-crystal display (LCD) grade glass substrate (550 x 650 mm) by means of two types of dc magnetron multi-chamber sputtering apparatus.
We developed the nanoindentation techniques to accelerate the characterization time for stress migration test. By AFM and cross-sectional TEM observations, we found an unusual three-layer structure in a Al-Cu thin film with strong anti-stress migration property.
Hydrogenated amorphous silicon thin-film transistors (a-Si:H TFTs) are now widely used as elements for active matrix liquid crystal displays. The nanometer-scale multilayered structure of a-Si:H TFTs has been characterized by cross-sectional transmission electron microscopy (TEM). The discrete layer construction of a faulty TFTs and the generation of defects during manufacturing processes have been investigated. A combination of focused ion beam (FIB) etching and cross-sectional TEM leads to a successful failure analysis. A contamination layer with a thickness of 10–30 nm and microvoids inside multilayers are identified in faulty TFTs. An a-Si layer on silicon nitride (SiNx) is crystallized during TEM observation. Electron energy loss spectroscopy analysis indicates that the diffusion of nitrogen into a-Si layer causes the crystallization.