Elevated Electron Temperature Coincident with Observed Fusion Reactions in a Sheared-Flow-Stabilized Z Pinch.

The sheared-flow-stabilized Z pinch concept has been studied extensively and is able to produce fusion-relevant plasma parameters along with neutron production over several microseconds. We present here elevated electron temperature results spatially and temporally coincident with the plasma neutron source. An optical Thomson scattering apparatus designed for the FuZE device measures temperatures in the range of 1-3 keV on the axis of the device, 20 cm downstream of the nose cone. The 17-fiber system measures the radial profiles of the electron temperature. Scanning the laser time with respect to the neutron pulse time over a series of discharges allows the reconstruction of the T_{e} temporal response, confirming that the electron temperature peaks simultaneously with the neutron output, as well as the pinch current and inductive voltage generated within the plasma. Comparison to spectroscopic ion temperature measurements suggests a plasma in thermal equilibrium. The elevated T_{e} confirms the presence of a plasma assembled on axis, and indicates limited radiative losses, demonstrating a basis for scaling this device toward net gain fusion conditions.

A multi-chord, two-color interferometer using Hilbert transform phase detection for measuring electron density in spheromak plasmas.

A new, four-chord, CO2/He-Ne heterodyne interferometer has been designed and built for measuring line-averaged plasma density in the HIT-SI3 and subsequent HIT-SIU sustained spheromak devices. The two-color system successfully eliminates vibration-induced errors caused by mirrors that are secured to the vacuum chamber and is able to resolve electron densities ne in the full operating range of 1018-1020 m-3 in both experiments with an integrated error of 4.7 × 1017 m-2. Data are presented from high toroidal current plasma discharges, showing the time evolution of electron densities ne and jϕ/ne along multiple chords.

High-speed feedback control of an oscillating magnetic helicity injector using a graphics processing unit.

A real-time control system has been developed to control the amplitude, phase, and offset of bulk plasma parameters inside an oscillating magnetic helicity injector. Control software running entirely on an Nvidia Tesla P40 graphical processing unit is able to receive digitizer inputs and send response patterns to a Pulse Width Modulation (PWM) controller with a minimum control loop period of 12.8 µs. With an input digitization rate of 10 MS/s, a three-parameter proportional integral differential controller is shown to be sufficient to inform the PWM controller to drive the desired oscillating plasma waveform with a frequency of 16.6 kHz that is located near the resonance of a coupled RLC circuit. In particular, the temporal phase of the injector waveform is held within 10° of the target value. Control is demonstrated over the toroidal modal structure of the imposed magnetic perturbations of the helicity injection system, allowing a new class of discharges to be studied.

Bilateral hippocampal increase following first-episode psychosis is associated with good clinical, functional and cognitive outcomes.

BACKGROUND: Hippocampal pathology has been proposed to underlie clinical, functional and cognitive impairments in schizophrenia. The hippocampus is a highly plastic brain region; examining change in volume, or change bilaterally, over time, can advance understanding of the substrate of recovery in psychosis. METHOD: Magnetic resonance imaging and outcome data were collected at baseline and 6-year follow-up in 42 first-episode psychosis subjects and 32 matched controls, to investigate whether poorer outcomes are associated with loss of global matter and hippocampal volumes. Bilateral hippocampal increase (BHI) over time, as a marker of hippocampal plasticity was hypothesized to be associated with better outcomes. Regression analyses were performed on: (i) clinical and functional outcomes with grey matter volume change and BHI as predictor variables; and (ii) cognitive outcome with BHI as predictor. RESULTS: BHI was present in 29% of psychosis participants. There was no significant grey matter loss over time in either patient or control groups. Less severe illness course and lesser symptom severity were associated with BHI, but not with grey matter change. Employment and global function were associated with BHI and with less grey matter loss. Superior delayed verbal recall was also associated with BHI. CONCLUSIONS: BHI occurs in a minority of patients following their first psychotic episode and is associated with good outcome across clinical, functional and cognitive domains.

Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study.

BACKGROUND: To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode. METHOD: One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re-evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls. RESULTS: At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035). CONCLUSIONS: We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data.

The differential effect of illicit drug use on cognitive function in first-episode psychosis and healthy controls.

OBJECTIVE: Illicit drug use can result in impairment in cognitive function in healthy individuals. Individuals with a psychotic disorder also show a deficit in cognitive function. Drug use may simply contribute to the characteristic cognitive deficit found in psychosis or alternatively result in a 'double deficit'. This study aims to investigate the association between drug use and cognitive function at the first-episode of psychosis and in community-matched controls. METHOD: One hundred and seventy-seven patients at the first episode of psychosis completed a battery of neuropsychological tests. Those that had used drugs in the previous year (n = 80) were compared with those who had not used drugs in the previous year (n = 97). A subsample of the first-episode psychosis patients were compared with community-matched controls (n = 110) according to drug-use status. RESULTS: Patients with a first episode of psychosis who had used drugs performed equally to those who had not used drugs on neuropsychological tests. In contrast, healthy controls who had used drugs in the previous year performed worse on tests of executive function and working memory compared with those controls that had not used drugs. CONCLUSION: There are differential associations of illicit drug misuse with cognitive function for first-episode psychosis patients and healthy controls.

Differing patterns of brain structural abnormalities between black and white patients with their first episode of psychosis

BACKGROUND: African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients. METHOD: We obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls. RESULTS: White British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus. CONCLUSIONS: We found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.

Differing patterns of brain structural abnormalities between black and white patients with their first episode of psychosis.

BACKGROUND: African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients. METHOD: We obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls. RESULTS: White British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus. CONCLUSIONS: We found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.

Minor physical anomalies in patients with first-episode psychosis: their frequency and diagnostic specificity.

BACKGROUND: An increased prevalence of minor physical anomalies (MPAs) has been extensively documented in schizophrenia but their specificity for the disorder remains unclear. We investigated the prevalence and the predictive power of MPAs in a large sample of first-episode psychotic patients across a range of diagnoses. METHOD: MPAs were examined in 242 subjects with first-episode psychosis (50% schizophrenia, 45% affective psychosis and 5% substance-induced psychosis) and 158 healthy controls. Categorical principal components analysis and analysis of variance were undertaken, and individual items with the highest loading were tested using the chi2 test. RESULTS: Overall facial asymmetry, assymetry of the orbital landmarks, and frankfurt horizontal significantly differentiated patients with schizophrenia and affective psychosis from controls, as did a 'V-shaped' palate, reduced palatal ridges, abnormality of the left ear surface and the shape of the left and right ears. Patients with affective psychosis had significantly lowered eye fissures compared with control subjects. CONCLUSIONS: MPAs are not specific to schizophrenia, suggesting a common developmental pathway for non-affective and affective psychoses. The topographical distribution of MPAs in this study is suggestive of an insult occurring during organogenesis in the first trimester of pregnancy.

Cathepsin D activity in human peripheral blood mononuclear leukocytes.

To investigate the cellular origins of cathepsin D (CD) in inflammatory lesions, the CD content of lymphocyte subsets, monocytes, and macrophages were compared. Human monocytes, B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes were separated from peripheral blood of normal donors. CD content was 0.13 +/- .01 micrograms equivalents of CD per million cells and significant differences between different cell types were not found. To determine the CD content of macrophages, differentiation of peripheral blood monocytes was induced by either in vitro culture or treatment with 4 beta-phorbol-12-myristate-13-acetate (PMA). Macrophages induced by five-day culture contained four times more CD than unstimulated monocytes, and macrophages induced by 18-h treatment with 20 mg/ml 4 beta-PMA contained nine times more CD than monocytes treated with 4 alpha-PMA, an inactive stereoisomer of 4 beta-PMA. These results suggest that macrophages are one of the enriched sources of CD in inflammatory lesions.

Activation of astrocytic lysosomal proteinases by factors released by mononuclear leukocytes.

Lysosomal proteinases are increased in the tissue lesions of experimental allergic encephalomyelitis and have been implicated in the degradation of myelin proteins. The cellular origins of the increased proteinases are not known but reactive astrocytes found in areas of increased activity are candidate cells. To evaluate the potential of astrocytes as the source of these proteinases, cathepsin B (CB) and cathepsin D (CD) levels were measured in lysates of cultured astrocytes from neonatal rats. Because astrocytes are activated by inflammatory mediators in demyelinating lesions the effect of activation on proteinase levels was examined. Culture supernatants from mononuclear leukocytes stimulated with either concanavalin A or phytohemagglutinin (PHA) induced significant increases in the astrocytic proteinases. Neither PHA alone, interleukin-1, interleukin-2, nor gamma-interferon induced significant increases. Fractions of the supernatant from PHA stimulated mononuclear leukocytes were tested and activity was found in fractions corresponding to a molecular weight of 45-50,000. These studies demonstrate that astrocytes contain significant amounts of CB and CD activity which can be increased by a factor or factors released by activated mononuclear leukocytes.

A dopamine receptor model and its application in the design of a new class of rigid pyrrolo[2,3-g]isoquinoline antipsychotics.

A hypothetical model of the interaction of antipsychotic drugs with the dopamine receptor is described. This three-dimensional molecular model has been developed on the basis of plausible intermolecular interactions between pharmacophoric groups of diverse types of antipsychotic drugs and postulated amino acid side chain substituents of the receptor protein. Three essential binding sites (one possibly required for antagonism) and one lipophilic auxiliary binding site are identified. The geometry is defined via the three-dimensional structures of drugs exhibiting receptor activity, including (R)-apomorphine, (+)-dexclamol, and molindone (whose crystal structure has been determined). A new conformationally rigid pyrrolo[2,3-g]isoquinoline derivative has been designed to conform to the receptor model. The compound (+/-)-1 (2,6-dimethyl-3-ethyl-4,4a,5,6,7,8,8a,9-octahydro-4a,8a-trans-1H-pyrrolo[2,3-g] isoquinolin-4-one; Ro 22-1319) exhibits potent antipsychotic-like activity. The activity is stereospecific, residing in the (-) enantiomer, predicted and confirmed by X-ray crystal structure analysis of (-)-1.HCl to have the 4aR,8aR absolute configuration.

Cost of a cardiac surgical and a general thoracic surgical patient to the National Health Service in a London teaching hospital.

The cost of the inpatient stay for a typical aortic valve replacement and for an oesophagectomy were determined by recording and costing every aspect of the patients' care from admission until discharge. This method of cost calculation was found to be satisfactory and could be used by other centres to allow comparisons between hospitals or countries. At St Thomas's Hospital in 1977 the cost of a cardiac operation was 2755 pounds, an oesophagectomy 1870 pounds, and a general surgical operation 564 pounds.