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Copy number variants (CNVs) have been associated with the risk of schizophrenia, autism and intellectual disability. However, little is known about their spectrum of psychopathology in adulthood.
Methods
We investigated the psychiatric phenotypes of adult CNV carriers and compared probands, who were ascertained through clinical genetics services, with carriers who were not. One hundred twenty-four adult participants (age 18–76), each bearing one of 15 rare CNVs, were recruited through a variety of sources including clinical genetics services, charities for carriers of genetic variants, and online advertising. A battery of psychiatric assessments was used to determine psychopathology.
Results
The frequencies of psychopathology were consistently higher for the CNV group compared to general population rates. We found particularly high rates of neurodevelopmental disorders (NDDs) (48%), mood disorders (42%), anxiety disorders (47%) and personality disorders (73%) as well as high rates of psychiatric multimorbidity (median number of diagnoses: 2 in non-probands, 3 in probands). NDDs [odds ratio (OR) = 4.67, 95% confidence interval (CI) 1.32–16.51; p = 0.017) and psychotic disorders (OR = 6.8, 95% CI 1.3–36.3; p = 0.025) occurred significantly more frequently in probands (N = 45; NDD: 39[87%]; psychosis: 8[18%]) than non-probands (N = 79; NDD: 20 [25%]; psychosis: 3[4%]). Participants also had somatic diagnoses pertaining to all organ systems, particularly conotruncal cardiac malformations (in individuals with 22q11.2 deletion syndrome specifically), musculoskeletal, immunological, and endocrine diseases.
Conclusions
Adult CNV carriers had a markedly increased rate of anxiety and personality disorders not previously reported and high rates of psychiatric multimorbidity. Our findings support in-depth psychiatric and medical assessments of carriers of CNVs and the establishment of multidisciplinary clinical services.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Dynamic surficial changes and changes in the position of the firn line and the areal extent of Hofsjökull ice cap, Iceland, were studied through analysis of a time series (1973–98) of synthetic-aperture radar (SAR) and Landsat data. A digital elevation model of Hofsjökull, which was constructed using SAR interferometry, was used to plot the SAR backscatter coefficient (σ°) vs elevation and air temperature along transects across the ice cap. Seasonal and daily σ° patterns are caused by freezing or thawing of the ice-cap surface, and abrupt changes in σ° are noted when the air temperature ranges from ∼−5° to 0°C. Late-summer 1997 σ° (SAR) and reflectance (Landsat) boundaries agree and appear to be coincident with the firn line and a SAR σ° boundary that can be seen in the January 1998 SAR image. In January 1994 through 1998, the elevation of this σ° boundary on the ice cap was quite stable, ranging from 1000 to 1300 m, while the equilibrium-line altitude, as measured on the ground, varied considerably. Thus the equilibrium line may be obscured by firn from previous years. Techniques are established to measure long-term changes in the elevation of the firn line and changes in the position of the ice margin.
We describe the design and performance of the Engineering Development Array, which is a low-frequency radio telescope comprising 256 dual-polarisation dipole antennas working as a phased array. The Engineering Development Array was conceived of, developed, and deployed in just 18 months via re-use of Square Kilometre Array precursor technology and expertise, specifically from the Murchison Widefield Array radio telescope. Using drift scans and a model for the sky brightness temperature at low frequencies, we have derived the Engineering Development Array’s receiver temperature as a function of frequency. The Engineering Development Array is shown to be sky-noise limited over most of the frequency range measured between 60 and 240 MHz. By using the Engineering Development Array in interferometric mode with the Murchison Widefield Array, we used calibrated visibilities to measure the absolute sensitivity of the array. The measured array sensitivity matches very well with a model based on the array layout and measured receiver temperature. The results demonstrate the practicality and feasibility of using Murchison Widefield Array-style precursor technology for Square Kilometre Array-scale stations. The modular architecture of the Engineering Development Array allows upgrades to the array to be rolled out in a staged approach. Future improvements to the Engineering Development Array include replacing the second stage beamformer with a fully digital system, and to transition to using RF-over-fibre for the signal output from first stage beamformers.
To investigate the feasibility of a national audit of epistaxis management led and delivered by a multi-region trainee collaborative using a web-based interface to capture patient data.
Methods:
Six trainee collaboratives across England nominated one site each and worked together to carry out this pilot. An encrypted data capture tool was adapted and installed within the infrastructure of a university secure server. Site-lead feedback was assessed through questionnaires.
Results:
Sixty-three patients with epistaxis were admitted over a two-week period. Site leads reported an average of 5 minutes to complete questionnaires and described the tool as easy to use. Data quality was high, with little missing data. Site-lead feedback showed high satisfaction ratings for the project (mean, 4.83 out of 5).
Conclusion:
This pilot showed that trainee collaboratives can work together to deliver an audit using an encrypted data capture tool cost-effectively, whilst maintaining the highest levels of data quality.
Hackerspaces are community-operated physical places where individuals get together to build things. While the organization itself is private, the ‘space’ that is created for individuals to work has elements of a common pool resource (CPR). The previous literature finds technology to be important in effective CPR management. Through an ethnographic study of a hackerspace, we show how technology is crucial for management of the ‘space’. In addition, we highlight how technology is used in hackerspaces to satisfy three of Ostrom's design principles for stable CPR management.
The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80–300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised.
With outdoor lighting ordinances in Arizona first in place around observatories in 1958 and 1972, then throughout the state since 1986, Arizonans have extensive experience working with communities and businesses to preserve our dark skies. Though communities are committed to the astronomy sector in our state, astronomers must collaborate with other stakeholders to implement solutions. Ongoing education and public outreach is necessary to enable ordinance updates as technology changes. Despite significant population increases, sky brightness measurements over the last 20 years show that ordinance updates are worth our efforts as we seek to maintain high quality skies around our observatories. Collaborations are being forged and actions taken to promote astronomy for the longer term in Arizona.
This study of the tree shrew, Tupaia belangeri, provides evidence for an intracollicular pathway that arises in the superficial gray layer and terminates in the optic layer. As a first step, Nissl, myelin, and cytochrome oxidase stains were used to identify the layers of the superior colliculus in the tree shrew. Second, anterograde and retrograde axonal transport methods were used to determine relationships between laminar borders and patterns of connections. Intraocular injections of wheat germ agglutinin conjugated to horseradish peroxidase showed that the border between the superficial gray and optic layers in the tree shrew is marked by a sharp decrease in the density of retinotectal projections. The optic layer also could be distinguished from the subjacent intermediate gray layer by differences in connections. Of the two layers, only the intermediate gray layer received projections following injections of wheat germ agglutinin conjugated to horseradish peroxidase within substantia nigra pars reticulata. Similarly, following injections of horseradish peroxidase or biocytin in the paramedian pons, the intermediate gray but not the optic layer contained labeled cells of origin for the main premotor pathway from the tectum, the predorsal bundle. Next, cells in the superficial gray layer were intracellularly injected with biocytin in living brain slices. Axons were traced from narrow and wide field vertical cells in the deep part of the superficial gray layer to the gray matter surrounding the fiber fascicles of the optic layer. Small extracellular injections of biocytin in brain slices showed that the optic layer gray matter contains a population of stellate cells that are in position to receive the input from the superficial layer. Finally, small extracellular injections of biocytin in the intermediate gray layer filled cells that sent prominent apical dendrites into the optic layer, where they may be directly contacted by the superficial gray layer cells. Taken together, the results support the hypothesis that the optic layer is functionally distinct from its adjacent layers, and may provide a link in the transfer of information from the superficial, retinal recipient, to the intermediate, premotor, layer of the superior colliculus.
These experiments were designed to test the idea that the optic layer in the tree shrew, Tupaia belongeri, is functionally distinct and provides a link between the visuosensory superficial and the premotor intermediate layers of the superior colliculus. First, cells in the optic layer were intracellularly labeled with biocytin in living brain slices. Compared to cells in the adjacent lower part of the superficial gray layer, which have apical dendrites that ascend toward the tectal surface, optic layer cells have dendritic fields that are restricted for the most part to the optic layer itself. The differences in dendritic-field location imply that superficial gray and optic layer cells have different patterns of input. The axons of optic layer cells terminate densely within the optic layer and, in addition, project in a horizontally restricted fashion to the overlying superficial gray and subjacent intermediate gray layers. This pattern also is different from the predominantly descending interlaminar projections of lower superficial gray layer cells. Next cells in the intermediate gray layer were labeled in order to examine the relationships between optic layer cells and these subjacent neurons that project from the superior colliculus to oculomotor centers of the brain stem Neurons in the upper part of the intermediate gray layer send apical dendrites into the optic layer and therefore can receive signals from the superficial gray layer either directly, from descending axons of lower superficial gray layer cells, or indirectly, through intervening optic layer cells. In contrast, lower intermediate gray layer cells have more radiate dendritic fields that are restricted to the intermediate gray layer. Thus, these lower cells must depend on descending projections from optic or upper intermediate gray layer cells for signals from the superficial gray layer. Together, these results support the idea that the optic layer is a distinct lamina that provides a link between the superficial and intermediate gray layers. They also are consistent with the traditional view that descending intracollicular projections play a role in the selection of visual targets for saccades.
Rabbit polyclonal hyperimmune antibodies to Yersinia pestis, and a mouse monoclonal antibody against the capsular antigen fraction 1 (F1) were compared in immunofluorescence (IF) tests. Fluorescent antibody conjugates were prepared from polyclonal antisera to four F1 positive Y. pestis strains; the conjugated antibody to strain A1122 gave the strongest IF staining of F1 positive and F1 negative Y. pestis strains. Indirect assays were rejected in favour of direct assays utilizing polyclonal and monoclonal reagents because the increased background staining reduced the effective contrast of bacterial visualisation. Polyclonal conjugates gave fairly homogeneous staining of Y. pestis bacterial populations, but in monoclonal assays a skew distribution of fluorescence intensity was observed, the majority of bacteria being poorly stained. The proportion of cells stained well by the monoclonal sufficed for easy identification of Y. pestis of the F1 positive phenotype however, and staining was not affected by washing the bacteria or treating them with formaldehyde. Y. pestis strains of the F1 positive genotype reacted with the monoclonal if bacteria were grown at 37 °C but not if the growth temperature was reduced to 25°C thus preventing capsule production. The polyclonal conjugate reacted with bacteria of these strains that had been grown at either temperature. Strains of F1 negative genotype grown at either temperature. Strains of F1 negative genotype grown at either temperature reacted with the polyclonal conjugate but not with the monoclonal. Cross reactions between the polyclonal reagents and Y. enterocolitica biovar 2, serovar O 8 could not be removed by selective absorption; however, the monoclonal antibody gave no cross reaction.
The F1 phenotypic status of bacterial preparations was verified by ELISA measurement of the fraction 1 antigen concentration. Antigen levels for F1 positive and F1 negative phenotypes differed by about three logs for suspensions of Y. pestis harvested from solid media.
The polyclonal and monoclonal direct IF tests applied to spleen and blood smears of laboratory mice infected with Y. pestis were able to differentiate between lethal infection with an F1 positive strain carrying all four classical virulence determinants, an F1 positive vaccine strain, and an F1 negative strain.
Literacy (i.e., the state of being literate) produces change both in individuals and in social groups (Akinnaso 1981, Ong 1982). Change through literacy may be realized in incresased skills and reasoning abilities, may be called improvement, and may be measured against established norms, or it many be measured by changed attitudes, belief systems, and cultural patterns (cf., Bendor-Samuel 1980).