Ultrathin thermoacoustic nanobridge loudspeakers from ALD on polyimide.

The recent development of low-temperature (<200 °C) atomic layer deposition (ALD) for fabrication of freestanding nanostructures has enabled consideration of active device design based on engineered ultrathin films. This paper explores audible sound production from thermoacoustic loudspeakers fabricated from suspended tungsten nanobridges formed by ALD. Additionally, this paper develops an approach to lumped-element modeling for design of thermoacoustic nanodevices and relates the near-field plane wave model of individual transducer beams to the far-field spherical wave sound pressure that can be measured with standard experimental techniques. Arrays of suspended nanobridges with 25.8 nm thickness and sizes as small as 17 µm × 2 µm have been fabricated and demonstrated to produce audible sound using the thermoacoustic effect. The nanobridges were fabricated by ALD of 6.5 nm Al2O3 and 19.3 nm tungsten on sacrificial polyimide, with ALD performed at 130 °C and patterned by standard photolithography. The maximum observed loudspeaker sound pressure level (SPL) is 104 dB, measured at 20 kHz, 9.71 W input power, and 1 cm measurement distance, providing a loudspeaker sensitivity value of ∼64.6 dB SPL/1 mW. Sound production efficiency was measured to vary proportional to frequency f 3 and was directly proportional to input power. The devices in this paper demonstrate industrially feasible nanofabrication of thermoacoustic transducers and a sound production mechanism pertinent to submicron-scale device engineering.

Thymic epithelial cells provide unique signals for positive selection of CD4+CD8+ thymocytes in vitro.

Using a novel system that supports positive selection in vitro, we have investigated the cellular requirements for this process by testing the ability of individual thymic and nonthymic stromal cell types to support the maturation of CD4+CD8+ thymocytes into CD4+ or CD8+ T cells. We show that thymic cortical epithelial cells are unique in their ability to mediate this maturation, and suggest that in addition to TCR ligation, these cells supply specific signals for positive selection. Moreover, by demonstrating positive selection on ECDI (1-ethyl-3-[3'dimethyl-aminopropyl]-carbodiimide)-fixed epithelial cells in this system, we provide direct evidence that the provision of these signals involves interactions with epithelial cell surface molecules rather than the release of soluble factors.

Manipulating walking path configuration influences gait variability and six-minute walk test outcomes in older and younger adults.

This study determined whether manipulations to walking path configuration influenced six-minute walk test (6MWT) outcomes and assessed how gait variability changes over the duration of the 6MWT in different walking path configurations. Healthy older (ODR) and younger (YNG) (n=24) adults completed familiarisation trials and five randomly ordered experimental trials of the 6MWT with walking configurations of; 5, 10 and 15m straight lines, a 6m by 3m rectangle (RECT), and a figure of eight (FIG8). Six-minute walk distance (6MWD) and walking speed (m.s(-1)) were recorded for all trials and the stride count recorded for experimental trials. Reflective markers were attached to the sacrum and feet with kinematic data recorded at 100 Hz by a nine-camera motion capture system for 5m, 15m and FIG8 trials, in order to calculate variability in stride and step length, stride width, stride and step time and double limb support time. Walking speeds and 6MWD were greatest in the 15m and FIG8 experimental trials in both groups (p<0.01). Step length and stride width variability were consistent over the 6MWT duration but greater in the 5m trial vs. the 15m and FIG8 trials (p<0.05). Stride and step time and double limb support time variability all reduced between 10 and 30 strides (p<0.01). Stride and step time variability were greater in the 5m vs. 15m and FIG8 trials (p<0.01). Increasing uninterrupted gait and walking path length results in improved 6MWT outcomes and decreased gait variability in older and younger adults.

P300 delay and attenuation in schizophrenia: reversal by neuroleptic medication.

BACKGROUND: P300 amplitude reduction in schizophrenia has been found by many investigators, but P300 latency generally has been reported to be normal; however, conflicting findings are present in the literature, and interpretation has been confounded by medication effects and methodological differences. METHODS: This study used a standard auditory oddball paradigm to compare the latency, amplitude, and topographic distribution of P300s in neuroleptic-free schizophrenic patients with those of healthy controls. The patients then were treated for 6 weeks with either remoxipride or haloperidol, and their P300s were reassessed. RESULTS: P300s were attenuated and delayed among neuroleptic-free patients. There was no evidence of peak lateralization or amplitude asymmetry over temporal areas. Subsequent neuroleptic medication normalized P300 latencies and increased P300 amplitudes, but the latter remained below normal limits over all except frontal areas. There were no correlations between P300 latency or amplitude and clinical symptomatology either before or after treatment. CONCLUSIONS: The finding of a P300 delay in neuroleptic-free schizophrenics that is normalized by neuroleptic medication has not been reported previously. Neuroleptic effects on P300 amplitude and latency appear to be independent of effects on clinical symptoms, and cannot be attributed to anticholinergic activity.

Three cases of carbamazepine toxicity.

The growing number of psychiatrists who prescribe carbamazepine therapy should be alert to the drug's potential complications. The authors report three such cases: one of hepatitis, one of a fatality due to aplastic anemia, and one of a severe dermatological reaction.

Studies on thymic epithelial cells in vitro.

Thymic epithelial cells are unique in their ability to support positive selection and are essential throughout thymocyte development. Here, we describe a technique for measuring the proliferation of thymic epithelial cells by flow cytometry using a combination of BrdU and pancytokeratin labelling, and we examine the effects of different in vitro culture strategies on thymic epithelial cell function. We find that at d15 gestation, 74% (+/- 0.4%) of thymic epithelial cells are in cycle, which declines to 63% (+/- 1.3%) by d16, and to 34% (+/- 1.9%) by d18. This decline in proliferation is also found in organ cultures and in cultures depleted of lymphoid cells by 2-dGuo, suggesting that the cell cycle status of thymic epithelial cells is independent of the lymphoid population. When cultured in vitro as 3-dimensional aggregates, purified MHC class II+ thymic epithelial cells retain the ability to support thymocyte maturation. In contrast, 2-dimensional monolayer culture abrogates the ability of these cells to support positive selection, causes a reduction in whn gene expression and reduces their ability to re-form coherent reaggregate structures. Intact lobes and 3-dimensional aggregates are therefore the best way of maintaining thymic epithelial cell function and gene expression in vitro.

Induction of apoptosis in thecal/interstitial cells: action of transforming growth factor (TGF) alpha plus TGF beta on bcl-2 and interleukin-1 beta-converting enzyme.

Follicular atresia is characterized by the initial rapid loss of granulosa cells by apoptosis, followed by the loss of thecal cells at a slower rate. We have previously shown that treatment of subconfluent cultures of thecal/interstitial cells (T/I) with transforming growth factor (TGF) alpha plus TGF beta caused chromatin condensation and internucleosomal fragmentation characteristic of apoptosis, whereas in the presence of either TGF alpha or TGF beta alone the cells remained healthy. In this study we have examined the effect of TGF alpha and TGF beta alone and in combination on the levels of mRNA encoding bcl-2 and interleukin-1 beta-converting enzyme (ICE) in T/I cells using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. Bcl-2, a cell survival gene, has been implicated in regulating the balance between cell proliferation and cell death in physiological processes. ICE, the homolog of the C. elegans cell death gene, ced-3, is also involved in apoptotic signal transduction. The levels of mRNA encoding specific PCR products for bcl-2 (430 bp) and ICE (453 bp) were amplified from T/I cell cDNA. Untreated T/I cells and TGF alpha- or TGF beta-treated cells contained comparable levels of bcl-2 mRNA. Treatment of T/I cells with TGF alpha plus TGF beta significantly decreased the levels of bcl-2 mRNA expression. TGF alpha plus TGF beta caused a significant decrease in bcl-2 mRNA levels within 3 h of treatment of T/I cells, followed by a progressive decline to 10% of control levels after 24 h of treatment. In contrast, in control T/I cells, the levels of ICE mRNA were low. TGF alpha plus TGF beta caused a progressive increase in ICE mRNA, reaching levels 2- and 3-fold higher than control cells after 5 and 7 h respectively. DNA analysis showed that DNA fragmentation, indicative of apoptosis, occurred after 10 h of treatment with TGF alpha plus TGF beta. These studies demonstrated that treatment of T/I cells with TGF alpha plus TGF beta influenced gene expression of bcl-2 and ICE prior to the time at which DNA fragmentation was observed. We propose that the gene products of bcl-2 and ICE are involved in the apoptotic signal transduction pathway induced by TGF alpha plus TGF beta in T/I cells.

Buspirone-induced jitteriness in three patients with panic disorder and one patient with generalized anxiety disorder.

Three patients with a history of panic disorder and one patient with a history of generalized anxiety disorder were treated with buspirone and experienced an increase in their anxiety levels, agitation, and restlessness and also developed pressured speech and racing thoughts. These symptoms completely resolved after buspirone was discontinued. Jitteriness may have been due to an unusual adrenergic sensitivity in these patients.

Medazepam and the driving ability of anxious patients.

A double-blind crossover trial of Medazepam was carried out in 14 anxious hospital patients. The mean self-adjusted dosage was 16.5 mg daily. The active drug was no more effective than placebo in relieving anxiety, which was rated both clinically and by the Middlesex Health Questionnaire (M.H.Q.) (Crown and Crisp, 1970). This may have been because the dose was relatively low for chronically anxious hospital patients. Even this dosage caused significantly higher scores on the M.H.Q. scale for depression. Braking and driving simulator tests were not adversely affected by Medazepam. In real driving conditions those taking the drug made significantly more technical, but not dangerous, errors. Pulse and blood pressure also were not affected.

HIV and the brain: evidence of early involvement and progressive damage.

AIDS is often accompanied by progressive encephalopathy and 'subcortical' dementia, but there is uncertainty regarding how early the brain involvement may begin in the course of HIV infection. This study used a cognitive auditory 'oddball' paradigm to elicit sensory and cognitive event related potential (ERP) components from healthy controls and from patients at different stages of HIV infection. Sensory component latencies did not differ between groups, but cognitive components showed progressive delays corresponding to increasingly severe clinical stages of HIV infection. The earliest changes were found among asymptomatic HIV + patients, suggesting that this test is a sensitive indicator of early subclinical CNS damage. In contrast, neither frequency analysis nor nonlinear dynamical analysis of the EEG showed differences between healthy controls and patients.

Tardive dyskinesia--diagnostic issues, subsyndromes, and concurrent movement disorders: a study of state hospital inpatients referred to a movement disorder consultation service.

Of 49 state hospital patients referred for movement disorder consultation for tardive dyskinesia (TD), 11 (23.9%) of 46 meeting inclusion criteria had movement disorders other than TD. These other disorders led to a false diagnosis of TD in 6 subjects (12.2%). Between-day dyskinesia variability affected TD ascertainment in only 3.2 percent of subjects. Prevalences of other neurological conditions in the 30 patients identified with definite TD were parkinsonism (90%), dystonia (25%), akathisia (16%), cerebellar signs (40%), dysmetria (23%), cerebellar tremor (17%), tardive dystonia (3.3%), and tardive akathisia (3.3%). Concurrence rates of parkinsonism with TD varied significantly according to which clinical signs were used to define parkinsonism. Using a rating score threshold of at least mild, rigidity occurred in 79.3 percent, bradykinesia in 55.2 percent, and resting tremor in 41.4 percent of subjects with TD; more significant rigidity occurred in 41.4 percent, bradykinesia in 31.0 percent, and resting tremor in 20.7 percent. Concurrence rates of neurological conditions with TD subsyndromes were distributed rather evenly according to condition prevalences, except for an association of cervicotruncal TD with bradykinesia (perhaps because of ventromedial striatal presynaptic and postsynaptic D2 blockade, respectively). These findings, as well as the occurrence of equal gender ratio and relative under-representation of bipolar and alcohol disorders in subjects with definite TD, are discussed.

Flash P2 delay in primary degenerative dementia of the Alzheimer type.

1. Flash visual evoked responses of 31 patients meeting DSM-III-R criteria for primary degenerative dementia of the Alzheimer type were compared with 31 healthy controls. 2. P1 latency was normal (75 +/- 6 msec Alzheimer's; 75 +/- 6 msec controls). 3. P2 was significantly delayed (162 +/- 32 msec, 147 +/- 20 msec, p < 0.03) among patients. 4. P1-P2 interpeak latency was significantly increased (87 +/- 32 msec, 71 +/- 21 msec, p < 0.03) among patients.

Reduction of dyskinesias and psychiatric disability with clozapine over different time courses.

Nine subjects with schizophrenia or schizoaffective disorder were treated with clozapine, 500 mg/day for at least 3 months. Each was affected by tardive dyskinesia whose severity was reduced significantly after 3 months of treatment but not at earlier monthly assessments. In contrast, psychiatric symptoms were lessened significantly after 1 month. The more delayed improvement of dyskinesia as compared to the pace of psychiatric improvement suggests a differential effect of the drug.

Which atypical antipsychotics are identified by screening tests?

Only two tests were specific for antipsychotic potential. All effective antipsychotics blocked pharmacologically induced locomotion and affected firing in the mesolimbic DA neurons. The remaining single- (Table 1) and repeated- (Table 2) dose tests identified the atypical antipsychotics. Clozapine, thioridazine, sulpiride, tiospirone, and molindone were atypical in both types of study. Pimozide, pipamperone, aceperon, methylperon, and clotiapine were atypical in single-dose studies, clopenthixol in repeated-dose studies. Since the biochemical abnormality causing psychoses is unknown, it may be that current methods of screening for new antipsychotics are inadequate and possibly inappropriate. If a neurotransmitter other than DA is the primary cause, then totally new tests may be needed. Present tests, especially those involving behavioral paradigms, may continue to select out compounds that cause EPS side-effects. New methods such as positron emission tomography scanning and other brain-imaging techniques hold the promise of studying specific types and subtypes of receptors in the living human brain. The recent discovery of chromosomal abnormalities in psychotic illness may provide new insights into the biochemical causes of such disorders and lead to completely new compounds that will be both safer and more effective. In the meantime we plan to review the literature on the clinical use of the compounds identified as atypical in this article and to develop research protocols to assess their efficacy in treatment-resistant psychoses and intractable conditions such as tardive dyskinesia.

Methylphenidate infusion in euthymic bipolars: effect of carbamazepine pretreatment.

A number of studies have reported attenuation by lithium (Li) pretreatment of the activating and euphoriant effects of psychostimulants. In view of increasing interest in the therapeutic potential of carbamazepine (CBZ) in bipolar disorder, we examined the effect of CBZ pretreatment on methylphenidate-induced behavioral activation and euphoria. Seven euthymic bipolar subjects received 2 weeks of pretreatment with CBZ or placebo in a double-blind crossover design. After each pretreatment period, the subjects received methylphenidate, 30 mg i.v.; mood and behavior changes were monitored for a period of 5 hours after each infusion. Methylphenidate induced a striking psychostimulant effect that was not attenuated by CBZ pretreatment. Possible implications of this finding for the antimanic efficacy of CBZ and for mechanisms of action are discussed.

Visual evoked responses in Alzheimer's disease: a review.

This review of the literature has shown that a delayed flash P2, in the presence of a normal flash P1 and pattern-reversal P100, can distinguish groups of Alzheimer's patients from groups who are healthy, psychiatrically ill, or suffering from other types of dementia. The VER's usefulness in the individual patient remains undetermined. With today's techniques, too many patients are misclassified. False negatives may result if Alzheimer's patients with visual symptoms are a distinct subgroup. Those with a normal flash VER may have cortical dysfunction outside the visual association areas. This would most likely be in the earliest stages of the disease before the atrophy becomes widespread. It may be that a VER test would only be valid in established disease. Future research should use adequate numbers of patients who are in a single category of mild, moderate or severe, so that the applicability of a VER test in the early stages of the disease can be determined. Strict diagnostic criteria such as the NINCDS-ADRDA guidelines should be used. Patients should be drug free, or at least not taking medications with anticholinergic properties. Flash VER should be obtained using a strobe light with eyes closed, and the pattern VER using a black and white television with a large pattern and high contrast.

A review of EEG biofeedback treatment of anxiety disorders.

Alpha, theta and alpha-theta enhancements are effective treatments of the anxiety disorders (Table 1). Alpha suppression is also effective, but less so (Table 2). Perceived success in carrying out the task plays an important role in clinical improvement. Research is needed to find out how much more effective they are than placebo, and which variables are important for efficacy. Variables needing study are: duration of treatment, type and severity of anxiety, number and type of EEG waveforms used, pretreatment with other kinds of feedback, position and number of electrodes, and presence of concomitant medication.