Zolpidem is differentiated from triazolam in humans using a three-response drug discrimination procedure

The discriminative stimulus effects of the imidazopyridine hypnotic zolpidem and the classic benzodiazepine hypnotic triazolam were examined in seven healthy volunteers using a three-response drug discrimination procedure and a within-subject design. During an initial sampling phase, the training drug conditions (placebo, 20 mg/70 kg zolpidem, and 0.5 mg/70 kg triazolam) were identified to subjects by letter codes before oral drug administration. During a subsequent training phase, subjects earned money for correct drug identifications made 3.75 h after drug administration. Five out of seven subjects acquired the three-response discrimination. Analyses of standardized and unstructured self-report questionnaires revealed that zolpidem and triazolam produced different profiles of effects; zolpidem was associated with a number of negative somatic symptoms including nausea, blurred vision, visual images/hallucinations, and heavy limbs, whereas triazolam was associated with greater sedative effects. These results demonstrate a distinct profile of discriminative stimulus and subjective effects for zolpidem, relative to triazolam, which is consistent with its somewhat distinct pharmacological profile, and provide evidence for the sensitivity of the three-response drug discrimination procedure for detecting between-drug differences.     

Response of mouse plantaris muscle to functional overload: comparison with rat and cat

Functional overload (FO) of a muscle by removing its synergists results in a compensatory hypertrophy of the muscle. However, the extent of the response appears to be dependent, at least in part, on the activity and/or loading levels of the muscle following surgery. Thus, differences in the inherent physical activity levels across species may be an important factor to consider. In the present study, the effects of 8 weeks of FO on the isometric mechanical properties of the plantaris of mice (highly active) were determined and the findings compared with the results from previous studies performed on the plantaris of rats (highly active) and cats (less active). FO resulted in approximately a doubling of the mass, the physiological cross-sectional area and the maximum tetanic tension per unit cross-sectional area, was similar in the plantaris of control and FO mice. Isometric twitch speed properties were unaffected, but the tension enhancement in response to an increase in the rate of stimulation showed the pattern of a "faster" muscle following FO. The fatigue resistance of the plantaris in FO mice was significantly higher than in control mice. Although the degree of hypertrophy that occurred in the mouse plantaris was similar to that observed after FO in rats and in cats that are exercised intermittently at high intensities, there were differences in the mechanical properties that may be related to the adaptability of species and/or the behavioral responses to the overload.     

Occurrence of transcranial Doppler high-intensity transient signals in patients with potential cardiac sources of embolism. A prospective study

BACKGROUND AND PURPOSE: Cerebral emboli can be recognized by typical "high-intensity transient signals" (HITS) in the transcranial Doppler (TCD) spectral curves. Patients with potential cardiac sources of embolism are at higher risk for stroke. METHODS: We examined the frequency of HITS in the left middle cerebral artery (MCA) with TCD over periods of 30 minutes in 100 patients having potential cardiac sources of embolism, as indicated by transthoracic or transesophageal echocardiography. RESULTS: Thirty-six (36%) of the patients presented with HITS. Sex, age, sufficient anticoagulation level, antiplatelet therapy, neurological symptoms, and a history of thrombosis had no influence on the prevalence and number of HITS. The patients with a single echocardiographic diagnosis were separated into eight echocardiographically defined groups: patients with (1) atrial fibrillation, (2) coronary artery disease plus ejection fraction of more than 30% including at least three wall segments of hypokinesia/akinesia, (3) coronary artery disease with less than 30% ejection fraction, (4) dilated cardiomyopathy, (5) infectious endocarditis, (6) aortic stenosis, (7) mitral stenosis, and (8) patent foramen ovale. A significant difference in HITS occurrence could not be found in any of the defined groups. Only patients with infectious endocarditis showed a tendency for a higher HITS prevalence. CONCLUSIONS: HITS are common phenomena in patients with potential cardiac sources of embolism. The clinical relevance of these HITS remains unclear.     

Addressing a state''s physician workforce priorities through the funding of graduate medical education: the TennCare model

OBJECTIVE: To investigate differences in second-, third-, and fourth-year medical students' knowledge of bloodborne pathogen exposure risks, as well as their attitudes toward, and intentions to comply with, Universal Precautions (UP). DESIGN: Cross-sectional survey. PARTICIPANTS AND SETTING: Surveys about students' knowledge, attitudes, and intentions to comply with UP were completed by 111 second-year (preclinical), 80 third-year, and 60 fourth-year medical students at Washington University School of Medicine in the spring of 1996. RESULTS: Preclinical students knew more than clinical students about the efficacy of hepatitis B vaccine, use of antiretroviral therapy after occupational exposure to human immunodeficiency virus, and nonvaccinated healthcare workers' risk of infection from needlestick injuries (P<.001). Students' perceived risk of occupational exposure to bloodborne pathogens and attitudes toward hepatitis B vaccine did not differ, but preclinical students agreed more strongly that they should double glove for all invasive procedures with sharps (P<.001). Clinical students agreed more strongly with reporting only high-risk needlestick injuries (P=.057) and with rationalizations against using UP (P=.008). Preclinical students more frequently reported contemplating or preparing to comply with double gloving, wearing protective eyewear, reporting all exposures, and safely disposing of sharps, whereas students with clinical experience were more likely to report compliance. Clinical students also were more likely to report having "no plans" to practice the first three of these precautions (P<.001). CONCLUSIONS: Differences in knowledge, attitudes, and intentions to comply with UP between students with and without clinical experience may have important implications for the timing and content of interventions designed to improve compliance with UP.     

An amino acid as a cofactor for a catalytic polynucleotide

Natural ribozymes require metal ion cofactors that aid both in structural folding and in chemical catalysis. In contrast, many protein enzymes produce dramatic rate enhancements using only the chemical groups that are supplied by their constituent amino acids. This fact is widely viewed as the most important feature that makes protein a superior polymer for the construction of biological catalysts. Herein we report the in vitro selection of a catalytic DNA that uses histidine as an active component for an RNA cleavage reaction. An optimized deoxyribozyme from this selection requires L-histidine or a closely related analog to catalyze RNA phosphoester cleavage, producing a rate enhancement of approximately 1-million-fold over the rate of substrate cleavage in the absence of enzyme. Kinetic analysis indicates that a DNA-histidine complex may perform a reaction that is analogous to the first step of the proposed catalytic mechanism of RNase A, in which the imidazole group of histidine serves as a general base catalyst. Similarly, ribozymes of the "RNA world" may have used amino acids and other small organic cofactors to expand their otherwise limited catalytic potential.     

Home use of a functional electrical stimulation system for standing and mobility in adolescents with spinal cord injury

OBJECTIVE: Functional electrical stimulation (FES) is a technology that may allow some patients with spinal cord injury (SCI) to integrate standing and upright mobility with wheelchair mobility. The purpose of this study was to document the patterns of home and community use of a FES system for standing and mobility. DESIGN: A telephone questionnaire was administered every 1 to 4 weeks for a minimum of 1 year. An interview was given at the end of the study to probe the motivators and barriers to home use. SETTING: Training for use of the FES system was performed in an inpatient pediatric rehabilitation setting. Data collection began after the subjects were discharged to home. PARTICIPANTS: Five adolescents with complete, thoracic-level SCI. INTERVENTION: Subjects participated in a program of FES exercise followed by training in basic mobility skills such as standing transfers, maneuvering, level ambulation, one-handed and reaching activities, and stair ascent/descent. MAIN OUTCOME MEASURE: The frequency with which the FES system was used at home and the activities for which it was utilized were documented. Motivators and barriers to FES home use were examined. RESULTS: Subjects donned the FES system on the average once every 3 to 4 days. Between 51% and 84% of the times donned, the system was used for exercise. The remaining times it was used for standing activities, most commonly reaching, one-handed tasks, and standing for exercise. "Motivators" included being able to do things that would otherwise be difficult, perceiving a healthful benefit or a sense of well-being from standing and exercise, and feeling an obligation to stand as a participant in a research study. "Barriers" to FES use included not finding time to use the system, having difficulty seeing opportunities to stand, and being reluctant to wear the FES system all day.     

A complexity measure for selective matching of signals by the brain

We have previously derived a theoretical measure of neural complexity (CN) in an attempt to characterize functional connectivity in the brain. CN measures the amount and heterogeneity of statistical correlations within a neural system in terms of the mutual information between subsets of its units. CN was initially used to characterize the functional connectivity of a neural system isolated from the environment. In the present paper, we introduce a related statistical measure, matching complexity (CM), which reflects the change in CN that occurs after a neural system receives signals from the environment. CM measures how well the ensemble of intrinsic correlations within a neural system fits the statistical structure of the sensory input. We show that CM is low when the intrinsic connectivity of a simulated cortical area is randomly organized. Conversely, CM is high when the intrinsic connectivity is modified so as to differentially amplify those intrinsic correlations that happen to be enhanced by sensory input. When the input is represented by an individual stimulus, a positive value of CM indicates that the limited mutual information between sensory sheets sampling the stimulus and the rest of the brain triggers a large increase in the mutual information between many functionally specialized subsets within the brain. In this way, a complex brain can deal with context and go "beyond the information given."     

Developing a dynamic project learning and cross‐project learning capability: synthesizing two perspectives

Driven by the complexity of new products and services, project work has become increasingly common in all types of organizations. However, research on project learning suggests that often project teams do not meet their stated objectives and, moreover, there is limited organizational learning from the experiences of project work. We use the dynamic capabilities framework to argue that building a dynamic project learning capability is useful for organizations that make extensive use of projects. We use both survey and interview data to discuss the key ways in which such a dynamic capability can be built. Our survey data demonstrate the importance of documenting project learning, but our interview data show that teams are often remiss at documenting their learning. The results from the two different approaches are synthesized using Boland & Tenkasi’s notions of perspective‐making and perspective‐taking. Importantly, combining the results from the two sets of data suggests that organizations need to emphasize the benefits from project reviews and documentation and explore ways in which the documents produced can be made more useful as boundary objects to encourage the sharing of learning across projects.     

Matching of Radiation with Array of Planar Antennas with SINIS Bolometers in an Integrating Cavity

Journal of Communications Technology and Electronics - Abstract—Arrays of planar annular antennas in the 345 GHz range with integrated superconductor–insulator–normal...