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DTI studies in schizophrenia have consistently reported decreased fractional anisotropy (FA, an index of white matter microstructure) in patients. There is little evidence as to the genetic or environmental determinants of this difference however. Studies of twins with schizophrenia allow us to estimate these influences. We report a cross-sectional case control study of twins with and without schizophrenia.
We recruited mono- and di-zygotic twins concordant and discordant for DSM schizophrenia from across the United Kingdom, referred by their treating psychiatrists. We recruited healthy control twins from the Institute of Psychiatry Volunteer Twin Register and by national media advertisements. Clinical diagnoses were confirmed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (Spitzer and Endicott, 1978). Zygosity was confirmed by DNA analysis. Eleven pairs of monozygotic twins concordant for schizophrenia, 10 pairs of monozygotic and seven pairs of dizygotic twins discordant for schizophrenia, 24 pairs of healthy monozygotic twins and 20 pairs of healthy dizygotic twins were recruited.
Subjects were scanned with an optimized DTI sequence at 1.5T. Scans were warp-corrected, masked, and FA calculated at each voxel. FA maps were then co-registered to a study-specific FA template using SPM2 and group differences calculated on segmented white-matter FA maps using non-parametric XBAM_v3.4.
Results are presented of analyses comparing twins with schizophrenia with their well co-twin, linear trend analyses comparing healthy controls with well di and mono-zygotic co-twins, and a heritability analysis of the healthy controls.
Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
Ziprasidone has modest QTc-prolonging effects, but it is not known whether this translates into an increased risk of cardiovascular events. To address this issue, a large, international, open-label, randomized, post-marketing study, the Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC), has been conducted to compare the cardiovascular safety of ziprasidone and olanzapine. Between February 2002 and February 2006, over 18,000 patients with schizophrenia from 18 countries were enrolled from a variety of psychiatry practice settings. A physician-administered questionnaire collected baseline information on demographics, medical and psychiatric history, and concomitant medication use. Data were self-reported by patients or reported by enrolling physicians. Descriptive baseline data on 18,094 patients with schizophrenia are presented here. Patients (mean age, 41.6 years; 55.1% male; 60.0% white) came primarily from the United States or Brazil (73.0%). Approximately 18% of patients had hypertension, 14.8% had hyperlipidemia, 46.5% currently smoked, 28.9% had a body mass index of ≥30 kg/m2, and 7.7% had diabetes at baseline; all of these characteristics are major cardiovascular risk factors. Mean time since schizophrenia diagnosis was 10.4 years, and average Clinical Impression Score was 5.2 (range, 1-8). At baseline, 71% of patients were using antipsychotic drugs. Although almost 80% of patients were using concomitant medications, less than 3% were using antihypertensive drugs or statins. In conclusion, the ZODIAC baseline data suggest that this study population has a substantial prevalence of cardiovascular risk factors and that hyperlipidemia and hypertension may be undertreated.
To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:
1. determine the extent to which this is altered in schizophrenia and
2. use a verbal fluency paradigm.
This is relevant since:
1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and
2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.
Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.
The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.
Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.
The heritability of the brain’s structure and function in schizophrenia remains elusive
To assess the influence of genetic and environmental factors on executive function in schizophrenia.
A twin-sibling study of 206 subjects; 163 twins, varying in their zygosity and concordance for schizophrenia, and 43 singletons from sibling clusters varying in their concordance for schizophrenia. We assessed performance and regional brain activation using functional magnetic resonance imaging, during a phonological verbal fluency task.
Patients and their unaffected relatives developed greater activation in the left inferior frontal gyrus, and greater deactivation in the middle temporal gyri bilaterally. These features were maximally evident in subjects with schizophrenia. When the analysis was restricted to the unaffected relatives and healthy controls, a similar pattern was evident. Heritability was greatest in the left hippocampus and the right middle temporal gyrus. Genetic modelling indicated a phenotypic correlation between schizophrenia and increased activity in the inferior frontal gyrus and reduced activity in the left middle temporal gyrus and left hippocampus, which appeared principally due to shared genetic effects.
Both schizophrenia and its familial vulnerability were associated with altered frontal, parahippocampal and temporal activation during verbal fluency. The altered left inferior frontal activity was particularly associated with schizophrenia, while altered left medial temporal and right middle temporal activity were more heritable. The latter was more intimately linked to the genetic risk for schizophrenia, and thus the better candidate intermediate phenotype.
Digitaria exilis is an important indigenous cereal in West Africa. The first fonio reference transcriptome was released and became a key tool for developing new molecular markers contributing to a better understanding of its genetic diversity. A total of 126 new putative primer pairs were successfully designed in 37,327 unigenes from the D. exilis transcriptome. Thirty-seven primer pairs were randomly selected and tested for their ability to cross-amplify to related species. Clear amplification patterns were observed on 24 primer pairs. Of these, 71, 74 and 35% showed polymorphism in three species: D. exilis, D. longiflora and D. iburua. The transferability from D. exilis was 96% to D. longiflora and 71% to D. iburua. The new SSR markers confirmed the close genetic proximity of D. exilis with D. longiflora and its stronger genetic difference of D. exilis from D. iburua. These markers will be valuable for completing future knowledge on Digitaria evolutionary history, and for testing gene flows between related species.
This paper extends the existing theories of directed technical change by allowing the factors of production, skilled, and unskilled workers, to be employed in both the skill-intensive and unskilled-intensive sectors. Consequently, the direction of technical progress and the sectoral allocation of factors are jointly determined. The feedback between technical progress and the allocation of factors leads to new results concerning structural change and directed technical change. An increase in the endowment of a factor leads to a dynamic reallocation of factors toward the sector that uses the factor intensively. The reallocation of factors also affects the stability properties of directed technical change. When the parameter conditions necessary for strong bias are satisfied, the interior regime (nonspecialization) is at most locally stable. More importantly, if the relative endowment of skilled labor becomes too high (low), the economy necessarily specializes in the production of skilled (unskilled)-labor-intensive goods. Last, the relationship between the relative endowment of skilled labor and the steady-state relative wage rate is not necessarily monotonic.
This article considers the relationship between audiotape's material affordances and the audibility of cultural practices. Not all changes in the materiality of sound media are audible to listeners, and not all changes in the audibility of cultural practices require changes in their material support. Thus focus on the affordances of sound technologies – those possibilities of sound technologies that may or may not be engaged by its users, and the wide range of practices that such technologies support – can help to connect materiality and audibility. I address the affordances of audiotape by examining a number of small case studies where established sonic practices encounter a transition from phonography to audiotape: musique concrète and the tape loop, serialist composition, and Les Paul's use of overdubbing. Finally, I consider the nature of the audiotape archive and its mode of access in order to pose some general questions about the meaning and use of audiotape's affordances.
Violence against women and girls (VAWG) is an urgent global health problem. Root causes for VAWG include the individual- and family-level factors of alcohol abuse, mental health problems, violence exposure, and related adverse experiences. Few studies in low- and middle-income countries (LMIC) have assessed the effectiveness of psychological interventions for reducing VAWG. This randomized controlled trial, part of the What Works to Prevent Violence Against Women and Girls consortium, examines the effectiveness of a common elements treatment approach (CETA) for reducing VAWG and comorbid alcohol abuse among families in Zambia.
Study participants are families consisting of three persons: an adult woman, her male husband or partner, and one of her children aged 8–17 (if available). Eligibility criteria include experience of moderate-to-severe intimate partner violence by the woman and hazardous alcohol use by her male partner. Family units are randomized to receive CETA or treatment as usual. The primary outcome is VAWG as measured by the Severity of Violence Against Women Scale, assessed along with secondary outcomes at 24 months post-baseline. Interim assessments are also conducted at 4–5 months (following CETA completion) and 12 months post-baseline.
This ongoing trial is one of the first in sub-Saharan Africa to evaluate the use of an evidence-based common elements approach for reducing VAWG by targeting a range of individual- and family-level factors, including alcohol abuse. Results of this trial will inform policy on what interventions work to prevent VAWG in LMIC with local perspectives on scale up and wider implementation.
Bovine viral diarrhea virus (BVDV) has long been associated with a wide variety of clinical syndromes and immune dysregulation, many which result in secondary bacterial infections. Current understanding of immune cell interactions that result in activation and tolerance are explored in light of BVDV infection including: depletion of lymphocytes, effects on neutrophils, natural killer cells, and the role of receptors and cytokines. In addition, we review some new information on the effect of BVDV on immune development in the fetal liver, the role of resident macrophages, and greater implications for persistent infection.
The World Heritage Site of Wanar in Senegal features 21 stone circles, remarkable not least because they were erected in the twelfth and thirteenth century AD, when Islam ruled the Indian Ocean and Europe was in its Middle Ages. The state of preservation has benefited the exemplary investigation currently carried out by a French-Senegalese team, which we are pleased to report here. The site began as a burial ground to which monumental stones were added, perhaps echoing the form of original funerary houses. Found in a neighbouring field were scoops left from the cutting out of the cylindrical monoliths from surface rock. While the origins of Wanar lie in a period of state formation, the monuments are shown to have had a long ritual use. The investigation not only provides a new context for one of the most important sites in West Africa but the precise determination of the sequence and techniques used at Wanar offers key pointers for the understanding of megalithic structures everywhere.
The partial contributions of reductions in fetal nutrition and oxygenation to slow fetal growth and a developmental origin of cardiovascular disease remain unclear. By combining high altitude with the chick embryo model, we have previously isolated the direct effects of high-altitude hypoxia on growth. This study isolated the direct effects of high-altitude hypoxia on cardiovascular development. Fertilized eggs from sea-level or high-altitude hens were incubated at sea level or high altitude. Fertilized eggs from sea-level hens were also incubated at high altitude with oxygen supplementation. High altitude promoted embryonic growth restriction, cardiomegaly and aortic wall thickening, effects which could be prevented by incubating eggs from high-altitude hens at sea level or by incubating eggs from sea-level hens at high altitude with oxygen supplementation. Embryos from high-altitude hens showed reduced effects of altitude incubation on growth restriction but not on cardiovascular remodeling. The data show that: (1) high-altitude hypoxia promotes embryonic cardiac and vascular disease already evident prior to hatching and that this is associated with growth restriction; (2) the effects can be prevented by increased oxygenation; and (3) the effects are different in embryos from sea-level or high-altitude hens.
Fifty-two Australian couples who had experienced the death of at least one member of a multiple birth (twin or higher order), with at least one survivor of that birth, were interviewed about their experiences at the time of the death, and since. This study compared parents' coping after the twins' deaths using the Beck Depression Inventory II, Perinatal Grief Scale, and unstructured interviews with some structured queries. Parents provided information on the influence of family, community and medical staff. According to retrospective reports, mothers experienced significantly more depression and grief than fathers at the time of loss. Both parents found the death of their twins grievous, but fathers, unlike mothers, were not encouraged to express their emotions. Although parents generally agreed about what helped them cope, fathers believed that they should be able to cope regardless of their grief. The strength of parents' spiritual beliefs had increased significantly since their loss, and there was some evidence that depressed and grieving mothers turned to spiritual support. Parents whose children died earlier reported levels of depression similar to those reported by parents whose children died later. To date, this is the largest study of grief in couples who have experienced the death of a twin and who have a surviving twin or higher order multiple.
Transition metal-doped ZnO bulk crystals and thin films have been investigated to determine the effects of transition metal incorporation on optical, magnetic, and structural properties of ZnO. A modified melt growth technique was used to grow bulk Zn1-xMnxO, Zn1-xCoxO, and Zn1-xFexO. Optical transmission measurements show an apparent shift in absorption edge with increasing transition metal incorporation. Raman spectroscopy also shows increasing lattice disorder with increasing transition metal concentration. ZnO thin films doped with Ni, Co, and Gd were grown by metalorganic chemical vapor deposition (MOCVD). While the Co-doped thin films showed antiferromagnetic behavior, magnetic hysteresis was observed in the Ni-doped and Gd-doped thin films. Structural quality was verified with X-ray diffraction (XRD), and optical properties were investigated using room temperature photoluminescence (PL) and optical transmission measurements. Properties of ZnO:TM bulk crystals and thin films are compared and used to discuss possible origins of ferromagnetism in these materials.
Mobile lice levels of two species of sea lice, Lepeophtheirus salmonis and Caligus elongatus, were examined on two samples of Atlantic salmon from the west coast of Ireland. The samples examined were taken two weeks apart from salmon caught by drift net in June 2003 at two different locations off the west coast of Ireland, one in the north-west and one in the west. Both samples of salmon caught were comparable in terms of numbers of total lice counted. No significant differences in male, female and ovigerous L. salmonis levels between the two samples were recorded, however, a significant difference was recorded between juvenile L. salmonis levels. Morphometric comparisons of male and ovigerous L. salmonis examined for each of the two salmon samples examined revealed some differences. There was a significant difference in male L. salmonis in terms of cephalothorax length between the samples. In the females significant differences were found between cephalothorax length, overall total length and egg length. Significant positive correlations within samples were also observed, between total female body length and both total egg number and egg string length in one of the samples examined.
PLANET, the Probing Lensing Anomaly NETwork, is an international team
conducting observations of on-going gravitational microlensing
events from five sites in the southern hemisphere. Our primary goal is to
detect or to put constraints on sub-stellar companions of M dwarfs from the galactic disk.
We report the current status and discuss the future prospects.
A 2 m robotic telescope at Dome C which would benefit from continuous coverage and dream like seeing
(median of 0.27 arcsec) is currently the best option for a
ground based aggressive search for Earth-mass planets in the habitable zone.
Quantum dots (QDs) have been shown to improve the efficiency and optical properties of opto- electronic devices compared to two dimensional quantum wells in the active region. The formation of self-assembled GaN nanostructures on aluminum nitride (AlN) grown on sapphire substrates by Metal Organic Chemical Vapor deposition (MOCVD) was explored. This paper reports on the effect of in-situ activation in nitrogen atmosphere on MOCVD grown GaN nanostructures. The effect of introducing manganese in these nanostructures was also studied. Optically active nanostructures were successfully obtained. A blue shift is observed in the photoluminescence data with a decrease in nanostructure size.
A trench-first dual damascene process has been developed for fat wires (1.26 μm pitch, 1.1 μm thickness) in a 0.18 μm CMOS process with copper/fluorosilicate glass (FSG) interconnect technology. The process window for the patterning of vias in such deep trenches depends on the trench depth and on the line width of the trench, with the worse case being an intermediate line width (lines that are 3X the via diameter). Compared to a single damascene process, the dual damascene process has comparable yield and reliability, with lower via resistance and lower cost.