A direct experimental comparison of single-crystal CVD diamond and silicon carbide X-ray beam position monitors.

Single-crystal chemical vapour deposition (CVD) diamond detectors are an established transmissive synchrotron beamline diagnostic instrument used for beam position and beam intensity monitoring. A recently commercialized alternative is silicon carbide (4H-SiC) devices. These have the potential to provide the same diagnostic information as commercially available single-crystal CVD diamond X-ray beam position monitors, but with a much larger transmissive aperture. At Diamond Light Source an experimental comparison of the performance of single-crystal CVD diamond and 4H-SiC X-ray beam position monitors has been carried out. A quantitative comparison of their performance is presented in this paper. The single-crystal diamond and 4H-SiC beam position monitors were installed in-line along the synchrotron X-ray beam path enabling synchronous measurements at kilohertz rates of the beam motion from both devices. The results of several tests of the two position monitors' performance are presented: comparing signal uniformity across the surface of the detectors, comparing kHz intensity measurements, and comparing kHz beam position measurements from the detectors. Each test is performed with a range of applied external bias voltages. A discussion of the benefits and limitations of 4H-SiC and single-crystal CVD diamond detectors is included.

Modelling the effects of optical vibrations on photon beam parameters using ray-tracing software.

A method to simulate beam properties observed at the beamline sample-point in the presence of motion of optical components has been developed at Diamond Light Source. A series of stationary ray-tracing simulations are used to model the impact on the beam stability caused by dynamic motion of optical elements. Ray-tracing simulations using SHADOW3 in OASYS, completed over multiple iterations and stitched together, permit the modelling of a pseudo-dynamic beamline. As beamline detectors operating at higher frequencies become more common, beam stability is crucial. Synchrotron ring upgrades to low-emittance lattices require increased stability of beamlines in order to conserve beam brightness. By simulating the change in beam size and position, an estimate of the impact the motion of various components have on stability is possible. The results presented in this paper focus on modelling the physical vibration of optical elements. Multiple beam parameters can be analysed in succession without manual input. The simulation code is described and the initial results obtained are presented. This method can be applied during beamline design and operation for the identification of optical elements that may introduce large errors in the beam properties at the sample-point.

A single-crystal diamond X-ray pixel detector with embedded graphitic electrodes.

The first experimental results from a new transmissive diagnostic instrument for synchrotron X-ray beamlines are presented. The instrument utilizes a single-crystal chemical-vapour-deposition diamond plate as the detector material, with graphitic wires embedded within the bulk diamond acting as electrodes. The resulting instrument is an all-carbon transmissive X-ray imaging detector. Within the instrument's transmissive aperture there is no surface metallization that could absorb X-rays, and no surface structures that could be damaged by exposure to synchrotron X-ray beams. The graphitic electrodes are fabricated in situ within the bulk diamond using a laser-writing technique. Two separate arrays of parallel graphitic wires are fabricated, running parallel to the diamond surface and perpendicular to each other, at two different depths within the diamond. One array of wires has a modulated bias voltage applied; the perpendicular array is a series of readout electrodes. X-rays passing through the detector generate charge carriers within the bulk diamond through photoionization, and these charge carriers travel to the nearest readout electrode under the influence of the modulated electrical bias. Each of the crossing points between perpendicular wires acts as an individual pixel. The simultaneous read-out of all pixels is achieved using a lock-in technique. The parallel wires within each array are separated by 50 µm, determining the pixel pitch. Readout is obtained at 100 Hz, and the resolution of the X-ray beam position measurement is 600 nm for a 180 µm size beam.

Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI).

Distributions of proton MR-detected metabolites have been mapped throughout the brain in a group of normal subjects using a volumetric MR spectroscopic imaging (MRSI) acquisition with an interleaved water reference. Data were processed with intensity and spatial normalization to enable voxel-based analysis methods to be applied across a group of subjects. Results demonstrate significant regional, tissue, and gender-dependent variations of brain metabolite concentrations, and variations of these distributions with normal aging. The greatest alteration of metabolites with age was observed for white-matter choline and creatine. An example of the utility of the normative metabolic reference information is then demonstrated for analysis of data acquired from a subject who suffered a traumatic brain injury. This study demonstrates the ability to obtain proton spectra from a wide region of the brain and to apply fully automated processing methods. The resultant data provide a normative reference for subsequent utilization for studies of brain injury and disease.

Differential brain responses when applying criterion attribute versus family resemblance rule learning.

Subsystems of category learning have been identified on the basis of general domains of content (e.g., tools, faces). The present study examined categories from the standpoint of internal structure and determined brain topography associated with expressing two fundamentally different category rule structures (criterion attribute, CA, and family resemblance, FR). CA category learning involves processing stimuli by isolated features and classifying by properties held by all members. FR learning involves processing stimuli by integral wholes and classifying on overall similarity among members without sharing identical features. fMRI BOLD response to CA and FR categorization was measured with pseudowords as stimuli. Category knowledge for both tasks was mastered prior to brain imaging. Areas of activation emerged unique to the structure of each category and followed from the nature of the rule abstraction procedure. CA categorization was implemented by strong target monitoring and expectation (medial parietal), rule maintenance in working memory, feature selection processes (inferior frontal), and a sensitivity to high frequency components of the stimulus such as isolated features (anterior temporal). FR categorization, consistent with its multi-featural nature, involved word-level processing (left extrastriate) that evoked articulatory rehearsal (medial cerebellar). The data suggest category structure is an important determinant of brain response during categorization. For instance, anterior temporal structures may help attune visual processing systems to high frequency components to support the learning of criterial, highly predictive rules.

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.

BACKGROUND: Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. METHODS: Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. RESULTS: Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. CONCLUSIONS: When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

Alveolar osteitis prevention by immediate placement of medicated packing.

OBJECTIVE: The purpose of this study was to evaluate whether immediate placement of medicated dry socket packing would decrease the incidence of alveolar osteitis (dry socket) with lower third molar extractions. STUDY DESIGN: In 100 patients, 200 lower third molars were extracted. One half of the sockets were packed to the crest of the alveolar ridge with a one-quarter-inch radiograph-detectable filament gauze that contained 9% eugenol, 36% balsam of Peru, and 55% petroleum jelly. The medicated packing was removed 1 week after surgery. None of the patients were taking antibiotics. Patients were instructed to increase their oral hygiene before and after surgery and were to use 0.12% chlorhexidine gluconate 2 days before and 3 days after surgery. RESULTS; Two hundred bilateral lower third molars of varying difficulty were extracted. The overall alveolar osteitis rate was 34 (17%). The immediately packed lower third molar sites had an alveolar osteitis rate of 8 (8%). The sockets that were not packed with medicated packing the day of surgery had an alveolar osteitis rate of 26 (26%). The difference was statistically significant (P =.001). CONCLUSION: The results of this study suggest that placement of medicated dry socket packing immediately after lower third molar extraction decreases the alveolar osteitis rate.

The effect of autonomic arousal on attentional focus.

This study investigates the effect of arousal on visual selection processes. Arousal is predicted to narrow the window of attention surrounding a point of focus. BOLD response to a letter discrimination task was measured under aroused (aversive noise) and non-aroused conditions (n = 8). Results revealed spatially distinct responses for trials invoking a narrow versus wide attentional focus. Under arousal a wide focus showed posterior thalamic activation similar to that associated with the narrowed attentional focus. This reflects altered stimulus filtering and supported the hypothesis. Relevant neuroanatomy involving the locus coeruleus and a triangular circuit of selective attention is discussed. The data demonstrates the intersection of arousal and visual stimulus selection systems, identifies a cognitive consequence of arousal, and provides the first fMRI evidence for brain stem autonomic arousal.

Feasibility of using fMRI to study mothers responding to infant cries.

While parenting is a universal human behavior, its neuroanatomic basis is currently unknown. Animal data suggest that the cingulate may play an important function in mammalian parenting behavior. For example, in rodents cingulate lesions impair maternal behavior. Here, in an attempt to understand the brain basis of human maternal behavior, we had mothers listen to recorded infant cries and white noise control sounds while they underwent functional MRI (fMRI) of the brain. We hypothesized that mothers would show significantly greater cingulate activity during the cries compared to the control sounds. Of 7 subjects scanned, 4 had fMRI data suitable for analysis. When fMRI data were averaged for these 4 subjects, the anterior cingulate and right medial prefrontal cortex were the only brain regions showing statistically increased activity with the cries compared to white noise control sounds (cluster analysis with one-tailed z-map threshold of P < 0.001 and spatial extent threshold of P < 0.05). These results demonstrate the feasibility of using fMRI to study brain activity in mothers listening to infant cries and that the anterior cingulate may be involved in mothers listening to crying babies. We are currently replicating this study in a larger group of mothers. Future work in this area may help (1) unravel the functional neuroanatomy of the parent-infant bond and (2) examine whether markers of this bond, such as maternal brain response to infant crying, can predict maternal style (i.e., child neglect), offspring temperament, or offspring depression or anxiety.

Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients.

OBJECTIVE: To determine whether the concentrations of the neuronal marker N-acetylaspartate (NAA) and the choline-containing metabolites (Cho) are altered in the subcortical brain of HIV+ patients who are cognitively normal and clinically asymptomatic, and to determine whether these alterations are greater in the presence of cognitive impairments and clinical symptoms. BACKGROUND: Pathologic studies suggest that subcortical gray matter carries a heavy HIV load, and neuropsychological test results are consistent with involvement of subcortical and frontostriatal brain systems in HIV disease. Noninvasive proton magnetic resonance spectroscopy (1H MRS) suggests neuronal preservation and macrophage infiltration in the subcortical brain of clinically symptomatic and cognitively impaired HIV+ individuals. Improved 1H MRS methods may allow the early detection of metabolite alterations in the subcortical brain of asymptomatic HIV+ individuals. METHODS: Two-dimensional 1H MRS imaging was performed on 30 HIV- control subjects and 70 HIV+ patients with varying severities of systemic disease and neuropsychological impairments, but without cerebral opportunistic infections. RESULTS: Subcortical Cho was elevated in HIV+ patients compared with control subjects regardless of the presence or absence of cognitive impairment or clinical symptoms. Subcortical NAA was lower than control NAA only in severely cognitively impaired HIV+ subjects. Subcortical NAA correlated with performance on a variety of neuropsychological tests but not with Centers for Disease Control clinical stage, whereas high-thalamic Cho was associated with low CD4 lymphocyte counts. CONCLUSIONS: 1H MRS imaging detects higher Cho in subcortical brain early in HIV disease, when individuals are clinically and neuropsychologically asymptomatic, whereas lower NAA is only found in subcortical brain in individuals with severe neuropsychological impairments. Quantitative 1H MRS imaging may play a role in the objective assessment of the presence, magnitude, and progression of brain involvement in HIV infection.

Cortical metabolite alterations in abstinent cocaine and cocaine/alcohol-dependent subjects: proton magnetic resonance spectroscopic imaging.

Chronic abuse of cocaine or alcohol is associated with structural, neuropathological and cognitive impairments that have been documented extensively. Little is known, however, about neurobiochemical changes in chronic substance abusers.We performed MRI and multi-slice brain proton magnetic resonance spectroscopic imaging (MRSI) to assess neuronal viability (via N-acetylaspartate (NAA)) and white matter metabolite status in 22 4-months-abstinent individuals dependent on crack cocaine only and on both crack cocaine and alcohol. Compared to 11 non-dependent controls we found (1) significantly lower NAA measures in the dorsolateral prefrontal cortex of the combined cocaine-dependent groups; (2) comparable spatial distribution and magnitude of these NAA effects for both cocaine-dependent groups; (3) higher choline-containing metabolites in frontal white matter of individuals dependent on both cocaine and alcohol; (4) absence of brain atrophy in both abstinent cocaine-dependent samples; and (5) partial recovery from prefrontal cortical NAA loss, primarily with abstinence from alcohol. The MRSI findings suggest preferential neuronal damage to the frontal cortex of both cocaine-dependent samples and gliosis in frontal white matter of individuals dependent on both alcohol and cocaine, conditions that persist for more than 4 months of abstinence.

Human herpesvirus-8 ORF K8.1 gene encodes immunogenic glycoproteins generated by spliced transcripts.

A cDNA library from phorbol ester-induced human herpesvirus-8 (HHV-8) carrying BCBL-1 cells was screened with an HIV+KS+ serum, and several cDNA clones encoding HHV-8 proteins were identified. Sequence analysis of two full-length cDNA clones show open reading frames (ORFs) encoded by spliced messages originating from the HHV-8 K8.1 gene. One cDNA encodes an ORF of 228 amino acids, designated K8. 1.A, with a cleavable signal sequence, a transmembrane domain, and four N-glycosylation sites. The splicing event generated the transmembrane domain in the ORF not seen in the genomic K8.1 ORF. Another cDNA encodes an ORF of 167 amino acids, designated K8.1.B, that shares similar amino and carboxyl termini with ORF K8.1.A but with an in-frame deletion. The primary translation products of ORF K8.1A (34 kDa) and K8.1B (20 kDa) in the in vitro-transcription-translation experiments shifted into glycosylated species of 43 and 32 kDa, respectively, in the presence of microsomal membranes. This suggested that the ORF K8.1A and K8.1B encode for glycoproteins. Riboprobes from the K8.1A cDNA insert hybridized with an HHV-8-specific 0.9-kb abundant transcript from BCBL-1 cells. Synthesis of this RNA was eliminated in the presence of a DNA synthesis inhibitor, suggesting that this RNA was a late gene transcript. Because ORFs K8.1A and K8.1B are unique for HHV-8, human sera were tested in Western blot reactions for antibodies against glutathione-S-transferase-ORF K8.1A fusion protein. All sera that were positive for HHV-8 antibodies in immunofluorescence assays with phorbol ester-induced BCBL-1 cells were also positive for anti-ORF K8.1A antibodies. This suggests that measurement of anti-ORF K8.1A antibodies would provide an HHV-8-specific serological assay. Further work is needed to define the biological role of the HHV-8 ORF K8.1A and K8.1B glycoproteins.

Identification and characterization of human herpesvirus-8 lytic cycle-associated ORF 59 protein and the encoding cDNA by monoclonal antibody.

Monoclonal antibody (Mab) 11D1 specific for HHV-8 showed a predominantly nuclear membrane fluorescence with about 30% of phorbol ester (TPA)-induced HHV-8-carrying BCBL-1 cells and with 2-8% of uninduced cells, but not with other herpes viruses infected cells. This Mab immunoprecipitated a 50-kDa polypeptide from BCBL-1 cells. The synthesis of this polypeptide was reduced but not inhibited by phosphonoacetic acid (PAA). A 2.3-kb cDNA insert from a cDNA library of TPA-induced BCBL-1 cells was identified by Mab 11D1. Sequence analysis shows that this cDNA is open at the 5' end and encodes two ORFs of 396AA (5' end) and 357AA (3' end). These ORFs are identical to the published HHV-8 ORFs 59 and 58, respectively in vitro transcription and translation of the cDNA resulted in the synthesis of a 50-kDa polypeptide and its partial peptide map was identical to that of the 50-kDa polypeptide detected in the TPA induced BCBL-1 cells. Riboprobe made from the cDNA insert hybridized with several viral specific RNAs from BCBL-1 cells. Levels of these RNA species were reduced, but not inhibited by PAA. These characteristics are similar to other herpes viruses genes encoding the lytic cycle associated early-late class accessory proteins that are essential for viral DNA replication. This Mab 11D1 recognizing the HHV-8 lytic cycle associated ORF 59 protein will be highly useful in monitoring the lytic replicative cycle.

Premorbid brain size is a determinant of functional reserve in abstinent crack-cocaine and crack-cocaine-alcohol-dependent adults.

Studies of Alzheimer's disease patients show that individuals with larger premorbid brains have a later onset of disease, or a lessened severity of cognitive impairment, or both. This may be due to a "functional reserve" associated with the greater number of neurons and synapses available in larger brains. We used magnetic resonance imaging and the MicroCog Assessment of Cognitive Functioning to examine the association between intracranial volume (premorbid brain size) and neuropsychological function in abstinent crack-cocaine and crack-cocaine-alcohol dependent individuals. There were no significant differences between the crack-only and the crack-alcohol dependent participants in neuropsychological performance or in intracranial volume. The abstinent cocaine-dependent individuals (both crack-only and crack-alcohol) were significantly impaired in many neuropsychological domains. Intracranial volume accounted for a significant proportion of the variance in neuropsychological performance. This result is consistent with the finding in the Alzheimer's literature that larger brains can maintain function to a greater degree, or for a longer period of time, in the face of cerebral disease or insult. Functional reserve may be a heretofore little recognized protective mechanism of the brain that has consequences for the severity of expression of cerebral disease or insult throughout life.

Abstinent chronic crack-cocaine and crackcocaine/alcohol abusers evidence normal hippocampal volumes on MRI despite persistent cognitive impairments.

We measured hippocampal volumes and cognitive functioning in crack-cocaine and crack-cocaine/alcoholdependent subjects (abstinent approximately 10-12 weeks) compared to age-matched controls. Cognitive function was evaluated using the computerized MicroCog Assessment of Cognitive Functioning (which includes tests of explicit, declarative memory subserved by the hippocampus). The hippocampal volumes were quantified on T1-weighted MRIs and were expressed as a proportion of intracranial vault volume. Both subjects and controls showed the larger right versus left hippocampal volume expected in normal anatomy, but we found no differences in hippocampal volume between any of the groups. However, both abstinent cocaine-dependent subjects and abstinent cocaine/alcohol-dependent subjects showed persistent cognitive impairments, including deficits in explicit memory. Our results suggest that either: (1) the hippocampus is resistant to structural volume loss in young and middle-aged cocaine or cocaine/alcohol-dependent subjects, (2) the hippocampal volume loss suffered by young and middle-aged cocaine or cocaine/alcohol-dependent subjects resolves after approximately 3 months of abstinence, or (3) hippocampal atrophy is obscured by the process of gliosis. Further, the cognitive impairments persisting in these abstinent cocaine and cocaine/alcohol-dependent samples may (1) be unrelated to hippocampal function or (2) be associated with abnormal hippocampal function that is not reflected in MRI measures of overall hippocampal atrophy.

Detection of human herpesvirus 8 DNA in Kaposi's sarcoma lesions and peripheral blood of human immunodeficiency virus-positive patients and correlation with serologic measurements.

Polymerase chain reaction (PCR) was used to examine human herpesvirus 8 (HHV-8) DNA from Kaposi's sarcoma (KS) lesions, normal skin, and peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients who did or did not have KS. Of 9 KS biopsies, 8 were positive for five HHV-8 open-reading frames and ranged from 1 viral genome per 2.5-12.7 cells. Two putative replicative gene RNAs were detected by reverse transcription-PCR at low levels in 1 KS lesion. HHV-8 DNA was detected in 4 of 8 PBMC samples from patients with KS and in 2 of 18 PBMC samples from patients without KS. Sera were tested for reactivity with BCBL-1 cells (HHV-8 positive): High immunofluorescence antibody titers against HHV-8 lytic and latent antigens were detected in samples from KS-positive patients, and >20 polypeptides from induced BCBL-1 cells were recognized. Sera from 6 of 18 patients without KS showed low levels of antibodies against HHV-8 lytic and latent antigens.