Mapping the evolving strain field during continental breakup from crustal anisotropy in the Afar Depression.

Rifting of the continents leading to plate rupture occurs by a combination of mechanical deformation and magma intrusion, yet the spatial and temporal scales over which these alternate mechanisms localize extensional strain remain controversial. Here we quantify anisotropy of the upper crust across the volcanically active Afar Triple Junction using shear-wave splitting from local earthquakes to evaluate the distribution and orientation of strain in a region of continental breakup. The pattern of S-wave splitting in Afar is best explained by anisotropy from deformation-related structures, with the dramatic change in splitting parameters into the rift axis from the increased density of dyke-induced faulting combined with a contribution from oriented melt pockets near volcanic centres. The lack of rift-perpendicular anisotropy in the lithosphere, and corroborating geoscientific evidence of extension dominated by dyking, provide strong evidence that magma intrusion achieves the majority of plate opening in this zone of incipient plate rupture.

Reduced connectivity of the auditory cortex in patients with auditory hallucinations: a resting state functional magnetic resonance imaging study.

BACKGROUND: Previous research has reported auditory processing deficits that are specific to schizophrenia patients with a history of auditory hallucinations (AH). One explanation for these findings is that there are abnormalities in the interhemispheric connectivity of auditory cortex pathways in AH patients; as yet this explanation has not been experimentally investigated. We assessed the interhemispheric connectivity of both primary (A1) and secondary (A2) auditory cortices in n=13 AH patients, n=13 schizophrenia patients without auditory hallucinations (non-AH) and n=16 healthy controls using functional connectivity measures from functional magnetic resonance imaging (fMRI) data. METHOD: Functional connectivity was estimated from resting state fMRI data using regions of interest defined for each participant based on functional activation maps in response to passive listening to words. Additionally, stimulus-induced responses were regressed out of the stimulus data and the functional connectivity was estimated for the same regions to investigate the reliability of the estimates. RESULTS: AH patients had significantly reduced interhemispheric connectivity in both A1 and A2 when compared with non-AH patients and healthy controls. The latter two groups did not show any differences in functional connectivity. Further, this pattern of findings was similar across the two datasets, indicating the reliability of our estimates. CONCLUSIONS: These data have identified a trait deficit specific to AH patients. Since this deficit was characterized within both A1 and A2 it is expected to result in the disruption of multiple auditory functions, for example, the integration of basic auditory information between hemispheres (via A1) and higher-order language processing abilities (via A2).

Brain surface contraction mapped in first-episode schizophrenia: a longitudinal magnetic resonance imaging study.

Schizophrenia is associated with structural brain abnormalities, but the timing of onset and course of these changes remains unclear. Longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive brain volume decreases in patients around and after the onset of illness, although considerable discrepancies exist regarding which brain regions are affected. The anatomical pattern of these progressive changes in schizophrenia is largely unknown. In this study, MRI scans were acquired repeatedly from 16 schizophrenia patients approximately 2 years apart following their first episode of illness, and also from 14 age-matched healthy subjects. Cortical Pattern Matching, in combination with Structural Image Evaluation, using Normalisation, of Atrophy, was applied to compare the rates of cortical surface contraction between patients and controls. Surface contraction in the dorsal surfaces of the frontal lobe was significantly greater in patients with first-episode schizophrenia (FESZ) compared with healthy controls. Overall, brain surface contraction in patients and healthy controls showed similar anatomical patterns, with that of the former group exaggerated in magnitude across the entire brain surface. That the pattern of structural change in the early course of schizophrenia corresponds so closely to that associated with normal development is consistent with the hypothesis that a schizophrenia-related factor interacts with normal adolescent brain developmental processes in the pathophysiology of schizophrenia. The exaggerated progressive changes seen in patients with schizophrenia may reflect an increased rate of synaptic pruning, resulting in excessive loss of neuronal connectivity, as predicted by the late neurodevelopmental hypothesis of the illness.

A comprehensive open reading frame phylogenetic analysis of isometric positive strand ssRNA plant viruses.

Rigorous large-scale whole genome comparisons are capable of providing more comprehensive and potentially more accurate descriptions of viral relationships, allowing for the effective validation and modification of current taxonomy. Using a set of 5 togaviruses as an outgroup, a comprehensive phylogeny for 115 isometric positive ssRNA plant viruses was generated based on the simultaneous comparison of over 480 ORFs found within completely sequenced genomes. With the exception of a diverse group of viruses representing the family Comoviridae, the single tree generated contained well supported branches corresponding to well established groups of viruses, including Bromoviridae, Umbravirus, Sobemovirus, and Tymoviridae. In addition, evidence for specific relationships between groups were also observed, specifically Tombusviridae + Umbravirus, and Luteoviridae + Sobemovirus. Various well established subgroups of viruses were also well resolved within the tree. In addition, some recent proposals involving the creation of new genera or the inclusion of newly described viruses into established genera were supported, while others were not. The evidence for frequent gene sharing and the potential consequences to viral taxonomy are discussed.

Magma-assisted rifting in Ethiopia.

The rifting of continents and evolution of ocean basins is a fundamental component of plate tectonics, yet the process of continental break-up remains controversial. Plate driving forces have been estimated to be as much as an order of magnitude smaller than those required to rupture thick continental lithosphere. However, Buck has proposed that lithospheric heating by mantle upwelling and related magma production could promote lithospheric rupture at much lower stresses. Such models of mechanical versus magma-assisted extension can be tested, because they predict different temporal and spatial patterns of crustal and upper-mantle structure. Changes in plate deformation produce strain-enhanced crystal alignment and increased melt production within the upper mantle, both of which can cause seismic anisotropy. The Northern Ethiopian Rift is an ideal place to test break-up models because it formed in cratonic lithosphere with minor far-field plate stresses. Here we present evidence of seismic anisotropy in the upper mantle of this rift zone using observations of shear-wave splitting. Our observations, together with recent geological data, indicate a strong component of melt-induced anisotropy with only minor crustal stretching, supporting the magma-assisted rifting model in this area of initially cold, thick continental lithosphere.

Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability.

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.

Spatial working memory ability is a marker of risk-for-psychosis.

BACKGROUND: Working memory has been identified as a core cognitive deficit in schizophrenia that is associated with negative symptoms, but it is unclear whether it is impaired prior to onset of psychosis in symptomatic patients. METHOD: Thirty-eight young people at ultra high-risk (UHR) of developing psychosis (of whom nine later became psychotic) were compared with 49 healthy controls on tests of spatial working memory (SWM) and delayed matching-to-sample (DMTS). RESULTS: Both SWM and DMTS performance was significantly poorer in the UHR groups. Those who later became psychotic generally performed more poorly than those who did not, although this did not reach significance for any measure. A significant association between SWM errors and negative symptoms was seen in the later-psychotic group only (P = 0.02). CONCLUSIONS: Spatial working memory abilities are impaired in those at high-risk for psychosis. The relationship between working memory and negative symptoms may be useful as a predictive tool.

Assessing the evidence on case management.

BACKGROUND: Evidence on the impact of case management is contradictory. AIMS: To discuss two different systematic reviews (one conducted by the authors and one conducted through the Cochrane collaboration) that came to contradictory conclusions about the impact of case management in mental health services. METHOD: We summarised the findings of the two reviews with respect to case management effectiveness, examined key methodological differences between the two approaches and discuss the impact of these on the validity of the results. RESULTS: The differences in conclusions between the two reviews result from the differences in inclusion criteria, namely non-randomised trials, data from unpublished scales and data from variables with skewed distributions. The theoretical and empirical effects of these are discussed. CONCLUSIONS: Systematic reviewers may face a trade-off between the application of strict criteria for the inclusion of studies and the amount of data available for analysis and hence statistical power. The available research suggests that case management is generally effective.

Visuospatial memory and learning in first-episode schizophreniform psychosis and established schizophrenia: a functional correlate of hippocampal pathology?

BACKGROUND: Despite a number of studies that have indicated impaired memory function in patients with schizophrenia, there have been few that have used a sensitive measure of right medial temporal lobe pathology. Given the reported findings of reduced hippocampal volume in schizophrenia, we used a theoretically sensitive test of the right medial temporal lobe to determine the nature of the visuospatial memory deficit in the disorder. METHODS: Seventy-six patients (37 with a first-episode schizophreniform psychosis, and 39 with established schizophrenia) were compared with 41 comparison subjects on a number of tests of visuospatial memory. These included spatial working memory, spatial and pattern recognition memory and a pattern-location associative learning test. RESULTS: Both patient groups displayed recognition memory deficits when compared to the comparison group. However, only those patients with established schizophrenia (of 9 years duration on average) were impaired on the associative learning test. CONCLUSIONS: The results indicate either a progressive decline in visuospatial associative learning ability over the course of the disorder, or that poor visuospatial associative learning is a marker for poor prognosis. In addition, these results have implications for our understanding of the role of the right medial temporal lobe in the pathophysiology of schizophrenia.

Frontal atrophy correlates with behavioural changes in progressive supranuclear palsy.

Regional brain volumes were measured in 21 patients with progressive supranuclear palsy (PSP), 17 patients with Parkinson's disease and 23 controls using 3D MRI-based volumetry. Cortical, subcortical and ventricular volume measures were correlated with global indices of motor disability and cognitive disturbance. All MRI measures, including hippocampal volume, were preserved in Parkinson's disease. Patients with PSP could be distinguished from both Parkinson's disease and controls by whole brain volume loss, ventricular dilatation and disproportionate atrophy of the frontal cortex. Caudate nucleus volume loss additionally differentiated PSP from controls, but was modest in severity and proportionate to whole brain volume loss. The present study identifies disease-specific differences in the topography of brain atrophy between PSP and Parkinson's disease, and has potential implications for the in vivo radiological differentiation of these two disorders. In PSP, the variance in frontal grey matter volume related to measures of behavioural disturbance, confirming the use of behavioural tests for ante-mortem case differentiation and suggesting that intrinsic cortical deficits contribute to these clinical disturbances.

A stable single-chain variable fragment expressing transfectoma demonstrates induction of idiotype-specific cytotoxic T-cells during early growth stages of a murine B-lymphoma.

The idiotypic determinants associated with the variable regions of antibody molecules are known to function as tumor-associated antigens (TAAs). However, there is no clear-cut evidence documenting their efficacy in inducing TAA-specific cytotoxic T-lymphocytes (CTLs). In most previous studies, idiopeptides were implicated in elicitation of TAA-specific CD4+ T-cells. Using a murine B-cell lymphoma, 2C3, we earlier demonstrated induction of splenic CD4+ and CD8+ T-lymphocytes directed to idiotypic Ig of the tumor. In the present study, we provide more direct evidence of the existence of Id-specific CTLs in the spleens of 2C3 bearing BALB/c mice using an scFv-transfectoma, P815A4, as a target. While both P815A4 and 2C3 cells were equally susceptible to cytolysis by the effector cells, lysis was evident only during early tumor progression. Moribund animals at the late stage of tumor growth failed to demonstrate any significant cytotoxic immune response against either tumor. Antibodies to MHC class I alleles Kd, Dd, Ld, beta2m and CD8 molecules all inhibited cytotoxicity. The CTL population from early tumor-bearers recognized 2C3 tumor in the context of all major H-2d alleles; however, in case of P815A4 cells, it was restricted to Kd and Dd alleles only. Based on these antibody inhibition studies, it appears that the idiopeptides generated in both tumors are in some way different, yet they were recognized equally by CTLs not only from the tumor-bearers but also by CTLs from 2C3-hyperimmune mice. It appears that scFv-containing transfectomas expressing antibody variable region epitopes would be useful for both elucidating CTL-defined idiopeptides and monitoring TAA-specific CTL response in tumor-bearing animals.

Can contrast sensitivity functions in dyslexia be explained by inattention rather than a magnocellular deficit?

We examined whether data demonstrating contrast sensitivity losses in dyslexia that have been interpreted as evidence for loss of magnocellular visual function could be explained by inattention. Computer simulations of observers with poor concentration yielded inflated estimates of threshold that were a constant proportion of the true threshold across spatial frequencies. Data from many, but not all, studies supporting the magnocellular deficit theory are well described by these simulations, which predicted no interaction between observer group and spatial frequency. Some studies have reported significant interactions, but suffer from statistical deficiencies. This compromises some of the evidence for a magnocellular deficit in dyslexia derived from studies of threshold contrast sensitivity.

A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia.

Brain abnormalities have been identified in patients with schizophrenia, but what is unclear is whether these changes are progressive over the course of the disorder. In this longitudinal study, hippocampal and temporal lobe volumes were measured at two time points in 30 patients with first episode psychosis (mean follow-up interval=1.9 years, range 0.54-4.18 years) and 12 with chronic schizophrenia (mean follow-up interval=2.3 years, range 1.03-4.12 years) and compared to 26 comparison subjects (mean follow-up interval 2.2 years, range 0.86-4.18 years). Hippocampal, temporal lobe, whole-brain and intracranial volumes (ICV) were estimated from high-resolution magnetic resonance images. Only whole-brain volume showed significant loss over the follow-up interval in both patient groups. The rate of this volume loss was not different in the first episode group compared to the chronic group. There were no changes in either hippocampal or temporal lobe volumes. The negative findings for the hippocampus and temporal lobes may mean that the abnormalities in these regions are stable features of schizophrenia. Alternatively, the period before the onset of frank psychotic symptoms may be the point of greatest risk for progressive change.

Selective bilateral hippocampal volume loss in chronic schizophrenia.

BACKGROUND: The hippocampus is implicated in the pathophysiology of schizophrenia; however, volumetric changes are subtle and have limited diagnostic specificity. It is possible that the shape of the hippocampus may be more characteristic of schizophrenia. METHODS: Forty-five patients with chronic schizophrenia and 139 healthy control subjects were scanned using magnetic resonance imaging. Hippocampi were traced manually, and two-dimensional shape information was analyzed. RESULTS: Two shape factors were found to be adequate to represent variance in the shape of the hippocampus. One of these factors, representing volume loss behind the head of the hippocampus, provided a degree of discrimination between patients with chronic schizophrenia and healthy control subjects; however, overall hippocampal volume following appropriate adjustment for brain volume showed a similar level of discrimination. Patients with chronic schizophrenia were best characterized using these two measures together, but diagnostic specificity was only moderate. CONCLUSIONS: This study identified that less of the hippocampus was distributed in its posterior two-thirds in patients with chronic schizophrenia, and specifically in the region just posterior to the hippocampal head. Group discrimination on the basis of hippocampal volume and shape measures was moderately good. A full three-dimensional analysis of hippocampal shape, based on large samples, would be a useful extension of the study.

Spatial working memory deficits in schizophrenia: relationship with tardive dyskinesia and negative symptoms.

OBJECTIVE: This study examined the interrelationship between negative symptoms, orofacial tardive dyskinesia, and specific neurocognitive processes, particularly those involved in memory and executive function, in patients with schizophrenia. METHOD: A set of computerized neurocognitive tasks, the Cambridge Neuropsychological Test Automated Battery, was used to assess executive and memory function in 54 hospitalized patients with chronic schizophrenia. Analysis of covariance was used to examine differences between groups with or without the topographical syndromes of orofacial tardive dyskinesia and between groups with high or low negative symptom scores. Principal-components and path analyses were used to examine further the influence of negative symptoms and orofacial tardive dyskinesia on performance on tests of memory and executive function. RESULTS: Both orofacial tardive dyskinesia and negative symptoms were significantly and independently associated with deficits on measures of spatial working memory span derived from principal-components analysis, but only orofacial tardive dyskinesia was associated with deficits on measures of spatial working memory strategy. Both were also associated with impairment on the delayed-matching-to-sample task, a test of memory. These associations were not explained by deficits in global intellectual function. Path analysis suggested that the relationships between the clinical symptoms and performance on the delayed-matching-to-sample task were mediated entirely through their relationship with the spatial working memory measures. CONCLUSIONS: In schizophrenia, orofacial tardive dyskinesia and evident negative symptoms are relatively independent markers of compromise of the cerebral systems that mediate spatial working memory. Candidate neural circuits include the frontal-striatal-thalamic systems, particularly those involving the dorsolateral prefrontal cortex.

A brief scale for assessing patients' satisfaction with care in outpatient psychiatric services.

OBJECTIVE: The authors evaluated the reliability and preliminary validity of the Charleston Psychiatric Outpatient Satisfaction Scale, a 15-item measure of patients' satisfaction designed for use in outpatient settings. The instrument uses a 5-point Likert-type response format that minimizes positive response bias and optimizes variability and predictive validity. METHODS: The Charleston Psychiatric Outpatient Satisfaction Scale was administered to 282 patients seen in psychiatric outpatient clinics affiliated with a public-academic psychiatric institution over a one-week period in 1995. RESULTS: The internal reliability of the instrument was high (alpha=.87), and its convergent validity was supported by the significant correlation of all items with anchor items that measured overall satisfaction with care and likelihood of recommending the clinic to others. The best predictors of overall ratings of care were the items measuring patients' satisfaction with helpfulness of the services and with the respect shown for patients' opinions about treatment. The best predictors of recommendation of the program to others were the items measuring satisfaction with matching of the treatment plan to patients' individual needs and with the respect shown for patients' opinions about treatment. Mean scores for all items ranged from 3.6 (satisfaction with parking) to 4.5 (satisfaction with helpfulness of the secretary and with the overall quality of care), indicating that overall satisfaction in this sample was high. CONCLUSIONS: The results provide preliminary support for the reliability and validity of the Charleston Psychiatric Outpatient Satisfaction Scale:

Acculturation and dental health among Vietnamese living in Melbourne, Australia.

OBJECTIVES: To describe the relationship between acculturation and oral health status, oral health knowledge and frequency of dental visits in subjects of Vietnamese background, 18 years or older, living in Melbourne, Australia. METHODS: Oral health status was measured using the DMFS index. Oral health knowledge was estimated by responses to six specific oral preventive measures: brushing, flossing, use of fluorides, diet, and dental visits. Dental visits was measured by the number of visits in the 12 months prior to the survey. Acculturation was measured along two dimensions, psychological and behavioural, using the Psychological-Behavioural Acculturation Scale. Data were analysed using multivariate analysis to identify the combined effect of eight predictors (age, gender, occupational status, education, reason for migration, proportion of life in the host country, behavioural acculturation and psychological acculturation) against the dependent variables. RESULTS: The analysis was conducted on a sample of 147 subjects and showed significant interactions between the acculturation variables and three outcome measures: dental caries, knowledge of preventive measures and dental visits. Results indicated that acculturation was an important intervening variable. Psychological acculturation was strongly related to the three oral health outcomes, although the effect of behavioural acculturation was also apparent regarding dental status. CONCLUSIONS: This study offers several insights for understanding the mechanisms by which acculturation impacts oral health status. Interventions that simplify the cultural influence of immigrant groups by focusing on socio-demographic differences and even immigration variables to define risk groups might not produce predicted changes in oral health status.

Hemispheric and gender-related differences in the gross morphology of the anterior cingulate/paracingulate cortex in normal volunteers: an MRI morphometric study.

The sulci and gyri found within the anterior cingulate (AC), and across the cerebrum generally, have been found to vary in location and complexity from one individual to the next, making it difficult to analyze imaging data accurately and systematically. In this study, we examined the nature of morphometric variance in the AC of the left and right cerebral hemispheres using high-resolution structural magnetic resonance imaging (MRI) acquired from 176 healthy volunteers. Depending on the presence of a paracingulate sulcus (PCS) and its antero-posterior extent, three types of AC patterns were identified: 'prominent', 'present' and 'absent'. Hemispheric comparisons across the whole sample showed the PCS to be more commonly 'prominent' in the left hemisphere and more commonly 'absent' in the right hemisphere. There was a significant gender difference, such that males showed an asymmetric pattern characterized by increased fissurization of the left AC, while females showed greater symmetry, with less fissurization of the left AC. Overall cerebral morphology, namely hemispheric volume and hemispheric fissurization, were also measured and used as independent variables as well as covariates in the analyses in order to ascertain the specificity of the results regarding AC morphology. Results showed that cerebral volume for males was larger on the right than on the left while fissurization showed the reverse asymmetry of greater leftward fissurization. In contrast, females were symmetric in both respects. The findings regarding AC morphology could not be explained by differences in these overall cerebral measures or by differences in age and handedness within the population. The results suggest that in the normal male brain, there exist morphological asymmetries at both the global and local levels that are less apparent in the female brain. The findings have implications for future studies examining the organization, development and functional anatomy of the AC.

An optimized method for estimating intracranial volume from magnetic resonance images.

The accuracy and efficiency of protocols to measure intracranial volume (ICV) from volumetric magnetic resonance imaging (MRI) studies has not been formally analyzed. The ICV of 30 control participants was obtained by tracing every slice of a MRI data set on which the cranial cavity appeared, and compared with estimated ICVs calculated by progressively selecting one of every x slices (i.e., "1-in-x") as a sampling strategy. The reliability and precision of each sampling strategy was then determined. There was virtually no reduction in reliability at the 1-in-10 sampling strategy, with a reliability exceeding 0.999. ICV can be confidently traced using a 1-in-10 sampling strategy, which should result in significant time savings.

A meta-analysis of the effectiveness of mental health case management over 20 years.

OBJECTIVE: Meta-analytical methods were used to investigate the effectiveness of case management and to compare outcomes for assertive community treatment and clinical case management. METHODS: Controlled studies of case management published between 1980 and 1998 were identified from reviews and through database searches. The results were quantitatively combined and compared with results of studies of mental health services without case management. Combined effect sizes and significance levels for 12 outcome domains were calculated. Analysis of homogeneity was used to explore differences between models. RESULTS: Forty-four studies were analyzed; 35 compared assertive community treatment or clinical case management with usual treatment, and nine directly compared assertive community treatment with clinical case management. Both types of case management were more effective than usual treatment in three outcome domains: family burden, family satisfaction with services, and cost of care. The total number of admissions and the proportion of clients hospitalized were reduced in assertive community treatment programs and increased in clinical case management programs. In both programs the number of hospital days used was reduced, but assertive community treatment was significantly more effective. Although clients in clinical case management had more admissions than those in usual treatment, the admissions were shorter, which reduced the total number of hospital days. The two types of case management were equally effective in reducing symptoms, increasing clients' contacts with services, reducing dropout rates, improving social functioning, and increasing clients' satisfaction. CONCLUSIONS: Both types of case management led to small to moderate improvements in the effectiveness of mental health services. Assertive community treatment had some demonstrable advantages over clinical case management in reducing hospitalization.