Nanoscale magnetic field detection using a spin torque oscillator.

Magnetic field detection with extremely high spatial resolution is crucial to applications in magnetic storage, biosensing, and magnetic imaging. Here, we present the concept of using a spin torque oscillator (STO) to detect magnetic fields by measuring the frequency of the oscillator. This sensor's performance relies predominantly on STO properties such as spectral linewidth and frequency dispersion with magnetic field, rather than signal amplitude as in conventional magnetoresistive sensors, and is shown in measured devices to achieve large signal to noise ratios. Using macrospin simulations, we describe oscillator designs for maximizing performance, making spin torque oscillators an attractive candidate to replace more commonly used sensors in nanoscale magnetic field sensing and future magnetic recording applications.

Compensatory strategies for acquired disorders of memory and planning: differential effects of a paging system for patients with brain injury of traumatic versus cerebrovascular aetiology.

BACKGROUND: Previous studies have demonstrated the effectiveness of paging systems in compensating for everyday memory and planning problems after brain injury, including in individuals with traumatic brain injury (TBI). METHODS: Here, in addition to further analyses of the TBI data from a previous randomised control crossover trial, results are reported from a sub-group of 36 participants with brain injury from cerebrovascular accident (CVA). RESULTS: Results indicate that, as with the TBI group, the pager was effective. However, the pattern of results following cessation of treatment differed. At a group level, TBI participants demonstrated maintenance of pager-related benefits, whereas CVA participants' performance returned to baseline levels. Comparisons of demographic and neuropsychological characteristics of the groups showed that the CVA group was older, had a shorter interval post-injury, and had poorer executive function than the TBI group. Furthermore, within the TBI group, maintenance was associated with executive functioning, such that executive dysfunction impeded maintenance. This correlation remained after controlling for demographic differences between groups. CONCLUSIONS: Together, these findings suggest that executive dysfunction may affect treatment-for example, whether or not temporary use of the pager is sufficient to establish a subsequently self-sustaining routine.

The European Brain Injury Questionnaire (EBIQ) as a reliable outcome measure for use with people with brain injury.

PRIMARY PURPOSE: There is a need to develop reliable outcome measures to determine well-being after brain injury. In 1997, Teasdale et al. published the European Brain Injury Questionnaire (EBIQ), a self-report and relative-report measure of the subjective experience of cognitive, emotional and social difficulties experienced by people with brain injury. It is now used in several rehabilitation centres as an outcome measure, but its test-re-test reliability has yet not been determined. The primary purpose of the present study is to establish this degree of reliability. RESEARCH DESIGN: The EBIQ was administered twice within an approximately 1-month period to 50 people with brain injury, to 20 relatives of people with brain injury and to 51 normal controls. RESULTS: The results showed significant and satisfactory test-re-test reliabilities for all three groups across all nine EBIQ scales (r = 0.55-0.90). CONCLUSION: It is concluded that the EBIQ is a clinically reliable measure to determine the subjective well-being of people with brain injury and to assess change of subjective concerns over time.

Using a paging system in the rehabilitation of encephalitic patients.

Memory and executive problems following encephalitis are common yet there are few published papers on the successful rehabilitation of such patients. We recently demonstrated (Wilson, Emslie, Quirk, & Evans, 2001; Wilson, Emslie, Quirk, Evans, & Watson, 2005) that a paging system could reduce the everyday memory and planning problems for people with non-progressive brain injury. Among the 143 patients who participated in the 2001 study were four people who had survived encephalitis. Their results are reported here. During a 2-week baseline, the successful task achievement of our four clients ranged from 2-81%. They then received a pager for 7 weeks and task achievement was documented in weeks 6 and 7. All were significantly more successful with the pager than they had been at baseline with success rates ranging from 45-96%. Five weeks after returning their pagers they were monitored once more. One of the encephalitic patients failed to achieve any of his target tasks, returning to baseline level, the other three dropped back a little but were still significantly more successful than at baseline. It is concluded that the paging system can reduce everyday memory and planning problems of patients with encephalitis.

Longitudinal assessment of awareness in early-stage Alzheimer's disease using comparable questionnaire-based and performance-based measures: a prospective one-year follow-up study.

Few studies of awareness in dementia have taken a longitudinal perspective, yet exploring the ways in which awareness changes over time may offer important information about the processes involved and the relationship between awareness and other variables. The present study explored in detail the patterns of change in awareness scores over time for a group of 12 participants with early-stage Alzheimer's disease using a multi-dimensional measure giving comparable participant-carer and post diction-performance discrepancy scores. There were small, non-significant increases in mean discrepancy scores for each of these components of the assessment, with similar patterns for questionnaire-based and performance-based ratings. The small changes that were observed reflected both participant and informant factors. The majority of participants showed only very minor changes; others showed changes in the direction of either reduced or increased awareness. There was no significant association between change in mean discrepancy score and change in MMSE score over time, although there was a significant decline in MMSE scores at follow-up. The observation of different longitudinal trajectories for awareness scores, reflecting increased or decreased awareness or no change, may indicate the operation of different processes affecting the expression of explicit awareness that can be understood within a biopsychosocial formulation of this complex construct.

A 5-year follow-up study of an atypical case of myotonic dystrophy.

This study presents 5-year follow-up data on NG, a woman with adult onset myotonic dystrophy and progressive cognitive decline who was first described by Wilson et al. The extent of the cognitive impairment is atypical of symptom-onset in adulthood and of paternal inheritance, both of which apply to this case. Together, the present and earlier studies report the results of regular neuropsychological assessments over a 16-year period. Severe impairment in executive functioning, episodic and semantic memory were apparent early in the history, while visuospatial skills and working memory were only mildly impaired after 16 years of follow-up. There was also a progressive dyslexia, initially characterized by the regularization errors typical of surface dyslexia, but subsequently dominated by visual/phonological reading errors. This pattern of impairment is not typical of myotonic dystrophy but resembles semantic dementia. Whilst the deficits may be attributable wholly to myotonic dystrophy pathology, the co-existence of a form of semantic dementia is also possible. It is noted that the aggregation of tau protein is a neuropathological feature common to both diseases.

Pasteurella multocida toxin as a tool for studying Gq signal transduction.

Pasteurella multocida toxin (PMT) stimulates and subsequently uncouples phospholipase C (PLC) signal transduction through its selective action on the Galphaq subunit. This review summarizes what is currently known about the molecular action of PMT on Gq and the resulting cellular effects. Examples are presented illustrating the use of PMT as a powerful tool for dissecting the molecular mechanisms involving pertussis toxin (PT)-insensitive heterotrimeric G proteins.

Emotional adjustment following cognitive recovery from 'persistent vegetative state': psychological and personal perspectives.

Previously, the cognitive recovery of a 26 year old woman, Kate, who developed a severe encephalomyelopathy and was in a 'minimally conscious/persistent vegetative state' for 6 months was reported. After 6 months, Kate began to respond to her environment and, at 2 years post-illness, neuropsychological assessment indicated that Kate was functioning within the normal range on tests of general intellectual functioning, executive functioning and most memory functions (with the exception of visual recognition memory). Although Kate has a severe dysarthria necessitating the use of a communication board and severe physical disabilities that require her to use a wheelchair, she has demonstrated an almost complete cognitive recovery and is among a tiny percentage of minimally conscious patients to do so. This single case report describes the emotional factors central to Kate's rehabilitation. Using a newly developed model of cognitive rehabilitation as a framework, the pivotal role that emotional and psychological factors played in Kate's adjustment to the consequences of her illness and the role of psychotherapeutic intervention in facilitating this adjustment are discussed.

Cognitive rehabilitation as a component of early intervention in Alzheimer's disease: a single case study.

Early intervention in Alzheimer's disease (AD) should focus on psychological and social needs as well as the provision of medication. One possible component of early intervention programmes for people with early-stage AD is cognitive rehabilitation aimed at fostering the development of strategies for coping with memory problems. The likely relevance of cognitive rehabilitation in early-stage AD is supported by neuropsychological and experimental learning studies, but further work is required to develop clinically relevant interventions, which can be applied in the real-life setting. This paper presents a single case intervention study in which a 66-year-old man with early-stage AD learned the names of 13 members of his support group using a mnemonic strategy coupled with either expanding rehearsal or repeated presentation, or both, within an errorless learning paradigm. Recall scores improved from a mean of 2.31% at initial baseline to 91.46% following intervention, and gains were largely maintained at follow-up. There was no evidence of any increase in depression, anxiety or caregiver strain during the intervention. The results support the view that cognitive rehabilitation interventions may form a valuable component of comprehensive early intervention programmes for people with AD.

Neurorehabilitation for two cases of post-traumatic stress disorder following traumatic brain injury.

INTRODUCTION: We present two cases to illustrate the assessment and management of post-traumatic stress disorder (PtSD) in the context of traumatic brain injury (TBI). Case KE suffered a TBI in a road traffic accident (RTA) in which his girlfriend was killed. Case CM survived a penetrating neurological injury from a severe knife attack. Both suffered cognitive difficulties, primarily in attention and memory, and selective visual impairments, and had endured significant losses of social role. METHOD: Within a neurorehabilitation programme, goals were set regarding management of their cognitive difficulties for regaining social roles and for the management of their PtSD symptoms. Cognitive behavioural therapy (CBT) was provided for managing PtSD symptoms, which included use of a stress inoculation and graduated exposure to avoided situations and trauma re-experiences. RESULTS: Both survivors reported significant improvements in managing mood state, and in redeveloping social roles. Objective measures confirmed significant gains from intervention. CONCLUSIONS: CBT, set within a neurorehabilitation programme, can lead to improvement in PtSD symptoms and psychosocial outcome in TBI survivors.

Brief report: prevalence of post-traumatic stress disorder symptoms after severe traumatic brain injury in a representative community sample.

PRIMARY OBJECTIVE: In this study, the authors investigated the prevalence of symptoms of post-traumatic stress disorder (PTSD) in a community sample of 66 survivors of severe traumatic brain injury (TBI). RESEARCH DESIGN, METHODS AND PROCEDURES: A representative sample of survivors of TBI were selected on the basis of having suffered significant disturbance in consciousness following their trauma event in the form of coma and/or post-traumatic amnesia. Neuropsychological testing confirmed that participants had suffered cognitive deficits consistent with severe brain injury. Participants were administered the Impact of Events inventory for symptoms of PTSD. MAIN OUTCOMES AND RESULTS: The authors found a prevalence rate of 18% for moderate-to-severe PTSD symptoms. CONCLUSIONS: PTSD symptoms are common following severe TBI. Further research is needed to establish protective and predictive factors for PTSD in TBI groups.

G(q/11) is involved in insulin-stimulated inositol phosphoglycan putative mediator generation in rat liver membranes: co-localization of G(q/11) with the insulin receptor in membrane vesicles.

Insulin signaling to generate inositol phosphoglycans (IPGs) was demonstrated to occur via the participation of the heterotrimeric G-proteins G(q/11). IPGs were measured as two specific inositol markers, myo-inositol and chiro-inositol after strong acid hydrolysis. Insulin and Pasteurella multocida toxin (PMT) generated both myo-inositol and chiro-inositol IPGs in a dose-dependent manner. PMT has been shown to activate G(q) specifically. Insulin action was abrogated by pre-treatment with anti G(q/11) antibody. Western blotting demonstrated the enrichment of both insulin receptor beta subunit and G(q/11) in the liver membrane vesicles. Vesicles also contained clathrin, caveolin PLC beta 1 and PLC Delta. Immunogold staining revealed the co-localization of both insulin receptor beta subunit and G(q/11) in an approximate stochiometric ratio of 1:3. No vesicles were detected with either component alone. The present and considerable published data provide strong evidence for insulin signaling both via a tyrosine kinase cascade mechanism and via heterotrimeric G-protein interactions.

Evaluation of accuracy and reliability of indirect calorimetry for the measurement of resting energy expenditure in healthy dogs.

OBJECTIVE: To assess accuracy and reliability of open-flow indirect calorimetry in dogs. ANIMALS: 13 clinically normal dogs. PROCEDURE: In phase 1, oxygen consumption per kilogram of body weight (VO2/kg) was determined in 6 anesthetized dogs by use of open-flow indirect calorimetry before and after determination of VO2/kg by use of closed-circuit spirometry. In phase 2, four serial measurements of VO2 and carbon dioxide production (VCO2) were obtained in 7 awake dogs by use of indirect calorimetry on 2 consecutive days. Resting energy expenditure (REE) was calculated. RESULTS: Level of clinical agreement was acceptable between results of indirect calorimetry and spirometry. Mean VO2/kg determined by use of calorimetry before spirometry was significantly greater than that obtained after spirometry. In phase 2, intraclass correlation coefficients (ICC) for REE and VO2 were 0.779 and 0.786, respectively, when data from all 4 series were combined. When the first series was discounted, ICC increased to 0.904 and 0.894 for REE and VO2, respectively. The most reliable and least variable measures of REE and VO2 were obtained when the first 2 series were discounted. CONCLUSIONS AND CLINICAL RELEVANCE: Open-flow indirect calorimetry may be used clinically to obtain a measure of VO2 and an estimate of REE in dogs. Serial measurements of REE and VO2 in clinically normal dogs are reliable, but a 10-minute adaption period should be allowed, the first series of observations should be discounted, multiple serial measurements should be obtained, and REE.

Cognitive recovery from "persistent vegetative state": psychological and personal perspectives.

This study reports on the case of a young woman who, at the age of 26, developed a severe encephalomyelopathy and was in a vegetative state or minimally conscious state for 6 months. She showed a sleep-wake cycle, but no evidence of cognitive functioning. Six months after her illness, she began to respond to her environment and eventually returned home to the care of her parents, with regular periods of respite care in a home for people with severe physical disabilities. She remains in a wheelchair with a severe dysarthria and communicates via a letter board. Two years after her illness, staff at the home requested an assessment of her cognitive functioning. On the WAIS-R verbal scale and the Raven's Progressive Matrices, the woman's scores were in the normal range. So too were her recognition of real versus nonsense words and her memory functioning (apart from a visual recognition memory test which was in the impaired range). Although she enjoyed the tests, she became distressed when asked about her illness and previous hospitalization. She was reassessed 1 year later, when there were few significant changes in her test scores but she could talk about her illness and hospitalization without becoming distressed. She was angry, however, about her experiences in the first hospital. Further tests suggested good executive functioning. In short, this woman's cognitive functioning is in the normal range for most tasks assessed, despite a severe physical disability and dysarthria, and despite the fact that she was vegetative for 6 months. Although some recovery following 6 months of being vegetative/minimally conscious is not unknown, it is rare, particularly for those with non-traumatic injuries, and the majority of people similarly affected remain with significant cognitive deficits. This client has, by and large, made an almost complete cognitive recovery. She feels positive about her life now and says the formal assessment showed people she was not stupid and this made her happy. The paper concludes with the young woman's own comments and views about what happened to her and her present feelings.

The effects of increased rehabilitation therapy after brain injury: results of a prospective controlled trial.

OBJECTIVE: The objective was to investigate the effect of increased intensity of rehabilitation therapy provided to brain-injured subjects on the rate at which independence was regained and the duration of hospital admission. DESIGN: A two-centre, prospective, controlled study with random allocation to groups. SETTING: Two district general hospitals on the south coast of England. SUBJECTS: Fifty-six people with moderate and severe head injury consecutively admitted to Southampton and Poole hospitals between June 1995 and September 1997. INTERVENTIONS: Increased intensity of rehabilitation therapy input without change in content. RESULTS: Subjects receiving more intensive therapy made more rapid progress and were discharged home sooner. The different intensities of therapy employed in this study showed no evidence of a 'ceiling' effect and the 'intervention group' made significantly more rapid progress on tests of dependency during the period of admission. A clear response to increased therapy input was seen in one of the centres with more rapid functional improvement and a shorter length of hospital stay. This centre already had more therapy and better community facilities. No such benefits were seen at the other centre where the intervention group had a longer hospital stay than the routine group. CONCLUSION: Increasing the hours per week of therapy given to adults recovering from brain injury in hospital can accelerate the rate of recovery of personal independence and result in their being discharged from hospital sooner. Increased rehabilitation therapy after brain injury is associated with enhanced functional recovery and shorter hospital stay if provided in the context of an integrated service that can provide ongoing community support. There is no evidence of any ceiling effect of therapeutic intensity beyond which no further response is observed.

Atrazine potentiation of arsenic trioxide-induced cytotoxicity and gene expression in human liver carcinoma cells (HepG2).

Recent studies in our laboratory indicated that arsenic trioxide has the ability to cause significant cytotoxicity, and induction of a significant number of stress genes in human liver carcinoma cells, HepG2. However, similar investigations with atrazine did not show any significant effects of this chemical on HepG2 cells, even at its maximum solubility of 100 microg/mL in 1% dimethyl sulfoxide (DMSO). Further cytogenetic studies were therefore carried out to investigate the combined effects of arsenic trioxide and atrazine on cell viability and gene expression in immortalized human hepatocytes. Cytotoxicity was evaluated using the MTT-assay for cell viability, while the CAT-Tox (L) assay was performed to measure the induction of stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG2), by creating stable transfectants of different mammalian promoter-chloramphenicol acetyltransferase (CAT) gene fusions. Cytotoxicity experiments yielded LC50 values of 11.9 +/- 2.6 microg/mL for arsenic trioxide in de-ionized water, and 3.6 +/- 0.4 microg/mL for arsenic trioxide in 100 microg/mL atrazine; indicating a 3 fold increase in arsenic toxicity associated with the atrazine exposure. Co-exposure of HepG2 cells to atrazine also resulted in a significant increase in the potency of arsenic trioxide to upregulate a number of stress genes including those of the glutathione-S-transferase Ya subunit--GST Ya, metallothioneinIIa--HMTIIA, 70-kDa heat shock protein--HSP70, c-fos, 153-kDa growth arrest and DNA damage (GADD153), 45-kDa growth arrest and DNA damage (GADD45), and 78-kDa glucose regulated protein--GRP78 promoters, as well as the xenobiotic response element--XRE, tumor suppressor protein response element--p53RE, cyclic adenosine monophosphate response element--CRE, and retinoic acid response element--RARE. No significant changes were observed with respect to the influence of atrazine on the modulation of cytochrome P450 1A1-CYP 1A1, and nuclear factor kappa (B site) response element--NFkappaBRE by arsenic trioxide. These results indicate that co-exposure to atrazine strongly potentiates arsenic trioxide-induced cytotoxicity and transcriptional activation of stress genes in transformed human hepatocytes.

Interaction of hand use and spatial selective attention in children.

It has been argued that concurrent motor action can modulate visual spatial attention. The visual spatial biases of adult patients with unilateral neglect, for example, can be ameliorated by simultaneous use of the contralesional hand. Such improvements are most dramatic when the contralesional hand is moved within contralesional space. To date, evidence of such an interaction in neurologically healthy individuals has not been presented. Line bisection is a simple task that is sensitive to attentional spatial bias. When young children are asked to bisect horizontal lines using their right hands, they show a reliable, if small, bias that is consistent with the pattern seen in adult neglect. This bias is reversed when the left hand is used. Here, we show that these effects are significantly modulated by the location of the movements relative to the body mid-line - specifically that the conjunction of hand movements within ipsilateral space is necessary for the previously reported pattern to be observed. We further demonstrate that these effects are not present in the bisections of neurologically healthy adults. In a final study, we examined whether the hand movement effects seen in children's line bisections would persist in a purely visual task (that is when the movements were made irrelevant to the response). Again, significant modulation of children's perception by concurrent hand movements - and the relative location of those movements - was observed. The theoretical and clinical implications of the results are discussed.

Transcriptional activation of stress genes and cytotoxicity in human liver carcinoma cells (HepG2) exposed to 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene.

The CAT-Tox (L) assay has recently been developed and validated for detecting and quantifying the specific molecular mechanisms that underlie toxicity of various xenobotic chemicals. We performed this assay to measure the transcriptional responses associated with 2,4,6-trinitrotoluene (TNT) and 2 of its byproducts [2,4 and 2,6-dinitotoluenes (DNTs)] to 13 different recombinant cell lines generated from human liver carcinoma cells (HepG2) by creating stable transfectants of mammalian promoter chloramphenicol acetyltransferase (CAT) gene fusions. Cytoxicity test with the parental HepG2 cells, using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]-based assay for cell viability, yielded LC50 values of 105 +/- 6 mg/mL for TNT in 1% dimethyl sulfoxide (DMSO), and > 300 mg/mL for DNTs, upon 48 h of exposure. TNT appeared to be more toxic than 2,4-DNT, which also showed a higher toxicity compared to 2,6-DNT. Of the 13 recombinant constructs evaluated, 8 (CYP 1A1, GST Ya, XRE, HMTIIA, c-fos, HSP70, GADD153, and GADD45), 5 (c-fos, HSP70, GADD153, GADD45, and GRP78), and none showed inductions to significant levels (p < 0.05), for TNT, 2,4-DNT, and 2,6-DNT, respectively. For most constructs, the induction of stress genes was concentration-dependent. These results show the potential for TNT and 2,4-DNT to cause protein damage and/or perturbations of protein biosynthesis (HSP70 and GRP78), alterations in DNA sequence or its helical structure (c-fos, GADD153, GADD45), and the potential involvement of TNT in the biotransformation process (CYP 1A1, GST Ya, XRE), and in the toxicokinetics of metal ions (HMTIIA). Within the range of concentrations tested (0-300 mg TNT or DNT/mL in 1% DMSO), no significant inductions (p > 0.05) of NFKBRE, p53RE, CRE, and RARE were found.