Search

At any particular moment, the energy security of an energy system is at risk from events, both external and internal, that can affect its operation. By analyzing these risks, the state of the system’s energy security can be determined. If the method is generic, it can be applied to any energy system and the entities that support its operation. Despite the potential benefits of such a method, a review of the literature shows that existing methods of analysis focus on, for example, limited parts of the system or specific types of energy. To address this shortcoming, this paper presents a method for analyzing the risks to the energy security of any entity in an energy system. The method, derived from work at the National Institute for Statistics and Technology (NIST), determines the risks to an entity using the well-known properties of events (rate-of-occurrence and expected stress) and entities (flows, time-to-recover, and stress-tolerance). The paper demonstrates how the method can be applied using both qualitative and quantitative data to measure, analyze, and potentially improve a system’s energy security. Several examples are included. [ABSTRACT FROM AUTHOR]

Energy security exists in an energy system until an event occurs which increases the stress on one or more of its entities. A resilient entity, designed to recover quickly from an event, will return the system (and, by extension, the affected entity) to its previous secure state. However, if the event occurs repeatedly or the time to recover is deemed too slow, or both, the system may remain in a high-stress, insecure state. In these situations, if the stress is to be reduced, the entity must be adapted to handle the event and put the system into a new, secure state. This paper applies research from a variety of disciplines to analyze the temporal effects of events on entities, and shows how resilience and adaptation contribute to the existence of energy security in energy systems. It underscores the importance of time when discussing the impact of events on an energy system and employs methods associated with reliability, notably mean time between failures (MTBF), mean time to recover (MTTR), and tolerance, to describe resilience and adaptation. The analysis is presented and discussed with examples using three common energy security indicators. [ABSTRACT FROM AUTHOR]

In order to maintain or improve a jurisdiction's energy security, its energy system needs to meet the demands of its energy services with affordable and preferably environmentally acceptable flows of energy. Since diversity can be a factor in the long-term survival of a system, having a diversity of energy flows is frequently treated as a proxy for energy security. This paper examines the relationship between energy security and the diversity of an energy system's energy flows using a set of energy security indicators and the Shannon-Wiener diversity index. Although diversity may be considered necessary for maintaining and improving energy security, the quantitative analysis of the relationship shows that an energy flow considered diverse need not be secure and that a secure energy flow need not be considered diverse. Examples of this relationship are included. These findings can prove useful to policy makers and energy analysts when developing transition strategies for a jurisdiction's energy system. [ABSTRACT FROM AUTHOR]

Highlights: [•] The kappa opioid receptor agonist (−)pentazocine was applied to the cochlea. [•] Sound evoked neural potentials were reduced in amplitude after drug treatment. [•] Endogenous dynorphin at biologically plausible levels has an inhibitory effect. [•] Higher (nonbiological) concentrations of drugs excite the auditory nerve. [•] Transmitter effects should be assessed at biologically plausible concentrations. [ABSTRACT FROM AUTHOR]

Interest in electrical energy storage is growing despite the many barriers preventing it from competing against technologies that provide similar services. While technical issues remain at the forefront, barriers also exist in the policy and regulatory sphere, but some potential solutions are being explored in North American jurisdictions. [Copyright &y& Elsevier]

Abstract: Energy systems change over time as events, such as grid failures, new energy sources, and extreme weather conditions, occur, often affecting the system's energy security. Understanding events, their causes, and how they are handled, can help a jurisdiction and its energy stakeholders develop better, evidence-based energy policy. This paper employs a definition of stress in combination with systems analysis to specify methods for explaining the states through which an energy process, chain, or system passes in response to an event and how this response results in energy security improving, deteriorating, or being maintained. The definition uses three dimensions-availability, affordability, and acceptability-derived from the International Energy Agency's definition of energy security to show when and how a system's energy security will change. Examples are used to illustrate the application of the methods. [Copyright &y& Elsevier]

Abstract: Auditory cortex (AI) shows age-related decreases in pre-synaptic markers for gamma-aminobutyric acid (GABA) and degraded AI neuronal response properties. Previous studies find age-related increases in spontaneous and driven activity, decreased spectral and directional sensitivity, and impaired novelty detection. The present study examined expression of GABAA receptor (GABAAR) subunit message, protein, and quantitative GABAAR binding in young, middle-aged, and aged rat AI, with comparisons with adjoining parietal cortex. Significant loss of GABAAR α1 subunit message across AI layers was observed in middle-aged and aged rats and α1 subunit protein levels declined in layers II and III. Age-related increases in GABAAR α3 subunit message and protein levels were observed in certain AI layers. GABAAR subunits, including β1, β2, γ1, γ2s, and γ2L, primarily, but not exclusively, showed age-related declines at the message and protein levels. The ability of GABA to modulate [3H]t-butylbicycloorthobenzoate binding in the chloride channel showed age-related decreases in peak binding and changes in desensitization kinetics. Collectively, age-related changes in GABAAR subunit composition would alter the magnitude and temporal properties of inhibitory synaptic transmission and could underpin observed age-related functional changes seen in the elderly. [Copyright &y& Elsevier]

Abstract: Two of the most significant challenges in the 21st century will be to improve energy security and reduce the greenhouse gas emissions associated with energy consumption. A co-beneficial solution to these challenges is seen as increasing the use of renewable energy for the production of electricity. Some renewable sources, such as wind are often presented as a way to reduce greenhouse gas emissions; however, since wind’s variability increases uncertainty and risk in expected generation, it can be detrimental to energy security. One of the ways in which wind’s contribution to a jurisdiction’s energy security and greenhouse gas reduction strategies can be improved is to employ a forecasting method that can help reduce risks. This paper proposes a method that applies risk and reliability analysis techniques to obtain the most-likely RL (Resistance–Load) scenario using a set of historical data for wind-supply or generation and load. RL estimates the reliability of a wind-energy system by simulating an anticipated resistance (the electrical generation) attempting to meet a load (the electricity demand) for a future year. The method is demonstrated through a case study and its results are compared with real-time data from a 12MW wind farm to prove its efficacy. [Copyright &y& Elsevier]

Many investigations in recent years have targeted understanding the genetic and biochemical basis of aging. Collectively, genetic factors and biological mechanisms appear to influence longevity in general and specifically; reduction of the insulin/IGF-1 signaling cascade has extended life span in diverse species. Genetic alteration of mammals for life extension indicates correlation to serum IGF-1 levels in mice, and IGF-1 levels have been demonstrated as a physiological predictor of frailty with aging in man. Longevity and aging data in the dog offer a close measure of the natural multifactorial longevity interactions of genetic influence, IGF-1 signaling, and environmental factors such as exposure, exercise, and lifestyle. The absence of genetic alteration more closely represents the human longevity status, and the unique species structure of the canine facilitates analyses not possible in other species. These investigations aimed to measure serum IGF-1 in numerous purebred and mixed-breed dogs of variable size and longevity in comparison to age, gender, and spay/neuter differences. The primary objective of this investigation was to determine plasma IGF-1 levels in the adult dog, including a wide range of breeds and adult body weight. The sample set includes animals ranging from just a few months of age through 204 months and ranging in size from 5 to 160 lb. Four groups were evaluated for serum IGF-1 levels, including intact and neutered males, and intact and spayed females. IGF-1 loss over time, as a function of age, decreases in all groups with significant differences between males and females. The relationship between IGF-1 and weight differs depending upon spay/neuter status, but there is an overall increase in IGF-1 levels with increasing weight. The data, currently being interrogated further for delineation of IGF-1 receptor variants and sex differences, are being collected longitudinally and explored for longevity associations previously unavailable in non-genetically modified mammals. [ABSTRACT FROM AUTHOR]

Abstract: Worldwide, many electricity suppliers are faced with the challenge of trying to integrate intermittent renewables, notably wind, into their energy mix to meet the needs of those services that require a continuous supply of electricity. Solutions to intermittency include the use of rapid-response backup generation and chemical or mechanical storage of electricity. Meanwhile, in many jurisdictions with lengthy heating seasons, finding secure and preferably environmentally benign supplies of energy for space heating is also becoming a significant challenge because of volatile energy markets. Most, if not all, electricity suppliers treat these twin challenges as separate issues: supply (integrating intermittent renewables) and demand (electric space heating). However, if space heating demand can be met from an intermittent supply of electricity, then both of these issues can be addressed simultaneously. One such approach is to use off-the-shelf electric thermal storage systems. This paper examines the potential of this approach by applying the output from a 5.15 MW wind farm to the residential heating demands of detached households in the Canadian province of Prince Edward Island. The paper shows that for the heating season considered, up to 500 households could have over 95 percent of their space heating demand met from the wind farm in question. The benefits as well as the limitations of the approach are discussed in detail. [Copyright &y& Elsevier]

Abstract: Presbycusis can be considered a slow age-related peripheral and central deterioration of auditory function which manifests itself as deficits in speech comprehension, especially in noisy environments. The present study examined neural correlates of a simple broadband noise stimulus in primary auditory cortex (A1) of young and aged Fischer–Brown Norway (FBN) rats. Age-related changes in unit responses to broadband noise bursts and spontaneous activity were simultaneously recorded across A1 layers using a single shank, 16-channel electrode. Noise bursts were presented contralateral to the left A1 at 80dB SPL. Aged A1 units displayed increased spontaneous (29%), peak (24%), and steady state response rates (38%) than did young A1 units. This was true across all A1 layers, although age-related differences were significantly greater for layers I–III (43% vs 18%) than lower layers. There was a significant age-related difference in the depth and duration of post-onset suppression between young and aged upper layer A1 units. The present functional differences across layers were consistent with studies showing greatest losses of gamma-aminobutyric acid (GABA) markers in superficial layers of A1 and with anatomic studies showing highest levels of inhibitory neurons located in superficial cortical layers. The present findings were also consistent with aging studies suggesting loss of functional inhibition in other cortical sensory systems. [Copyright &y& Elsevier]

Abstract: Aims: The type 2 muscarinic receptor (M2R) differs from the other G-protein-coupled muscarinic receptor (type 4, or M4R) in tissue distribution and physiologic effects. We studied the impact of these receptors on sleep and arousal by using M2R and M4R knock-out (KO) mice. Main methods: M2R and M4R KO and genetically intact mice were compared in terms of normal patterns of sleep, responses to sleep loss, infectious challenge and acoustic startle, and acoustic prepulse inhibition of startle (PPI). Key findings: Under basal conditions, M2R and M4R KO mice do not differ from the background strain or each other in the amount or diurnal pattern of sleep, locomotor activity, and body temperature. After enforced sleep loss, M2R KO mice, in contrast to the other two strains, show no rebound in slow-wave sleep (SWS) time, although their SWS is consolidated, and they show a greater rebound in time spent in REMS (rapid-eye-movement sleep) and REMS consolidation. During influenza infection, M2R KO mice, as compared with the other strains, show marked hypothermia and a less robust increase in SWS. During Candida albicans infection, M2R KO mice show a greater increase in SWS and a greater inflammatory response than do the other strains. M2R KO mice also show greater acoustic startle amplitude than does the background strain, although PPI was not different across the 3 strains over a range of stimulus intensities. Significance: Taken together, these findings support different roles for M2R and M4R in the modulation of sleep and arousal during homeostatic challenge. [Copyright &y& Elsevier]

In this paper, a leader's style of humor delivery is proposed to have an influence on followers' positive emotions (e.g., joy, contentment, pride in one's work), and subsequent creative performance. Extant literature is also presented in support of the proposition that humor delivery will have a positive effect on followers' creativity and innovation. Positive emotions are proposed to mediate the relationship between humor and creative performance. [ABSTRACT FROM AUTHOR]

Abstract: Free radical formation in the cochlea plays a key role in the development of noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant formation of both reactive oxygen species and reactive nitrogen species 7–10 days after noise exposure. Reduction in cochlear blood flow as a result of free radical formation has also been described. Here we report that the antioxidant agents vitamins A, C, and E act in synergy with magnesium to effectively prevent noise-induced trauma. Neither the antioxidant agents nor the magnesium reliably reduced NIHL or sensory cell death with the doses we used when these agents were delivered alone. In combination, however, they were highly effective in reducing both hearing loss and cell death even with treatment initiated just 1 h before noise exposure. This study supports roles for both free radical formation and noise-induced vasoconstriction in the onset and progression of NIHL. Identification of this safe and effective antioxidant intervention that attenuates NIHL provides a compelling rationale for human trials in which free radical scavengers are used to eliminate this single major cause of acquired hearing loss. [Copyright &y& Elsevier]

Abstract: The fusiform cell and deep layers of the dorsal cochlear nucleus (DCN) show neurotransmitter and functional age-related changes suggestive of a downregulation of inhibitory efficacy onto DCN output neurons. Inhibitory circuits implicated in these changes include vertical and D-multipolar cells. Cartwheel cells comprise a large additional population of DCN inhibitory neurons. Cartwheel cells receive excitatory inputs from granule cell parallel fibers and provide a source of glycinergic inhibitory input onto apical dendrites of DCN fusiform cells. The present study compared the response properties from young and aged units meeting cartwheel-cell criteria in anesthetized rats. Single unit recordings from aged cartwheel cells revealed significantly higher thresholds, increased spontaneous activity and significantly altered rate-level functions characterized by hyperexcitability at higher intensities. Aged cartwheel cells showed a significant reduction in off-set suppression. Collectively, these findings suggest a loss of tonic and perhaps response inhibition onto aged DCN cartwheel neurons. These changes likely reflect a compensatory downregulation of synaptic inhibition in response to a loss of excitatory drive from auditory and non-auditory excitatory inputs via granule cells. The impact of increased excitability of cartwheel cells on DCN output neurons is likely to be complex, influenced by loss of glycinergic release and/or subunit receptor changes which would only partially off-set age-related loss of inhibition onto the somata and basal dendrites of fusiform cells. [Copyright &y& Elsevier]

Abstract: Layer-V pyramidal cells comprise a major output of primary auditory cortex (A1). At least two cell types displaying different morphology, projections and in vitro physiology have been previously identified in layer-V. The focus of the present study was to characterize extracellular receptive field properties of layer-V neurons to determine whether a similar breakdown of responses can be found in vivo. Recordings from 105 layer-V neurons revealed two predominant receptive field types. Thirty-two percent displayed strong excitatory V/U-shaped receptive field maps and spiking patterns with shorter stimulus-driven interspike intervals (ISIs), reminiscent of the bursting cells discussed in the in vitro literature. V/U-shaped maps remained relatively unchanged across the three sequential repetitions of the map run on each neuron. Neurons with V/U-shaped maps were also easily depolarized with extracellular current pulse stimulation. In contrast, 47% of the neurons displayed Complex receptive field maps characterized by weak and/or inconsistent excitatory regions and were difficult to depolarize with current pulses. These findings suggest that V/U-shaped receptive fields could correspond to previously described intrinsic bursting (IB) cells with corticotectal projections, and that neurons with Complex receptive fields might represent the regular spiking (RS) cells with their greater inhibitory input and corticocortical/corticostriatal projection pattern. [Copyright &y& Elsevier]

Mice develop changes in sleep during the nonspecific immune response that occurs during the initial few days after inoculation with influenza virus. T lymphocytes, neutrophils, macrophages, and natural killer (NK) cells all participate in the early host response to influenza infection. All of these cell types are potential sources of endogenous substances that modulate sleep, but the contributory role of each cell type to the alteration of somnolence during infection has not been determined. To investigate which cell types contribute to the sleep enhancement that develops during influenza infection in mice, the sleep patterns of C57BL/6J mice with perturbations of particular facets of host immune response capabilities were assessed before and after influenza infection. Targeted mutation of the gene Ccl3 (macrophage inflammatory protein 1α)) prevented development of the dark phase sleep enhancement that is characteristic of C57BL/6J mice after influenza infection. Other experimental treatments that impair macrophage or monocyte function also produced significant (administration of pentoxifylline or CNI-1493) or marginally significant (deletion of the interferon-gamma gene or intranasal administration of carrageenan) changes in influenza-induced sleep enhancement in C57BL/6J mice. In contrast, functional impairments of NK cells, neutrophils, and T lymphocytes did not significantly influence sleep responses. These data therefore support a contributory role for macrophages, but not for NK cells, neutrophils, and T lymphocytes, in eliciting the sleep response typical of influenza-infected C57BL/6J mice. [Copyright &y& Elsevier]

Objective: This study examined the clinical features of patients with clinical diagnoses of probable Alzheimer disease (AD), possible AD, and uncertain.Design: Case study comparing three groups of AD patients diagnosed at their initial visit to an Alzheimer outpatient clinic.Setting: Southern Illinois University School of Medicine's Center for Alzheimer Disease and Related Disorders (CADRD) assessment sites (20) in rural Illinois.Participants: 300 patients assessed at CADRD between January 1, 1994 and July 1, 2000.Measurements: Patients were given an extensive clinical battery consisting of physical and neurologic examination, mental status testing including the Mini-Mental State Exam (MMSE), Short Blessed Dementia (SBD) and Blessed Dementia Scale (ADL), medical history evaluation, and laboratory tests. Other data included age at visit, gender, and medical history variables.Results: Mean MMSE, SBD, and ADL scores differed significantly between groups (p's < 0.01). In all three cognitive tests, the uncertain group was the least impaired while the probable AD group was the most impaired. A Rasch model indicated that only the cognitive measures were useful in discriminating between the three diagnostic groups.Conclusion: In general, probable AD patients were distinguished from possible AD patients by the severity of their dementia as measured by the MMSE, ADL and SBD as well as Hachinski-Ischemic Score (HIS) scores. A Rasch model did well at predicting group membership based upon dementia measures only. The uncertain group differed from the AD groups in age and dementia severity as measured by the MMSE, ADL and SBD. Noting differences between this and previous studies, we speculate disparity may be related to differences in population ethnicity. [ABSTRACT FROM AUTHOR]

Objective Since patients with dementia with Lewy bodies (DLB) tend to have greater impairment of attention and construction and better memory ability on neuropsychological tests than patients with Alzheimer's disease (AD), we determined if the items that measure attention, memory, and construction in the Mini-Mental State Examination (MMSE) help to distinguish DLB from AD early in the course of the dementia. Design We retrospectively studied the first available MMSE exam for each of our patients with DLB or AD and compared their MMSE subscores for attention, memory, and construction. Setting A university dementia brain bank in central Illinois, USA. Patients All patients with neuropathologically-proven DLB or AD with MMSE scores≥13. Results We identified 17 DLB and 27 AD patients for whom we had MMSE exams. The attention and construction subtest scores of the DLB group were worse (p =0.0071 and p =0.0038, respectively) than those of the AD group. The memory subscores of the DLB group were better, although the difference did not reach statistical significance (p =0.22). When a mathematical equation was used to combine the three subscores with equal weighting ($Attention-{5\over 3}\;Memory+5\cdot Construction$), the scores of the DLB group were worse (p =0.00007). Using this equation, a score less than 5 points was associated with DLB with a sensitivity of 0.82 (95% Confidence Interval (CI)=0.57–0.96) and a specificity of 0.81 (95% CI=0.62–0.94). Conclusions Our findings support the work of others regarding the relative neuropsychological impairments of DLB and AD and indicate that the MMSE may be helpful in the differentiation of DLB and AD. Copyright © 2002 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Operating systems is an example of a subject that, with the right tools, can be taught in an applied manner, giving students the opportunity to understand, and hence appreciate, the fundamentals of commercial operating systems such as Unix and Windows. Not surprisingly, the tools needed in an operating systems course are, at a minimum, a hardware testbed and a programming language into which algorithms can be translated. This paper describes how many of the salient points concerning operating systems, such as concurrency and critical regions, can be covered in an applied manner using the PC, the C programming language, and extensions to C. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one on the discussion of teaching the fundamentals of hardware and software to computer science students and another on the development of computer application software.

Presents a letter to the editor on the use of the Mini-Mental State Examination to differentiate Alzheimer's disease from dementia with Lewy bodies.

Objective: To determine the capability of patients with Alzheimer's disease (AD) and age-matched controls to discriminate and recognize odorants equilibrated for strength and familiarity, and to determine if immediate corrective-feedback can improve performance in either task. Major results: No significant differences between elderly controls (EC) and AD patients were apparent for the discrimination task regardless of feedback condition. The EC group outperformed the AD group on the recognition task. Feedback enhanced EC group performance but failed to benefit the AD group. Conclusions: Early in the disease process, AD subjects have a deficit in processing olfactory cues at levels beyond that necessary for discrimination. This deficit is specifically related to the olfactory system and is in addition to any general cognitive deficits they may have. Feedback is ineffective for AD subjects but can greatly enhance the performance of the intact elderly on tasks requiring the verbal mediation of olfactory cues. [ABSTRACT FROM AUTHOR]

Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs. [ABSTRACT FROM AUTHOR]

Age-related hearing loss frequently results in a loss in the ability to discriminate speech signals, especially in noise. This is attributable, in part, to a loss in temporal resolving power and ability to adjust dynamic range. Circuits in the adult dorsal cochlear nucleus (DCN) have been shown to preserve signal in background noise. Fusiform cells, major DCN output neurons, receive focused glycinergic inputs from tonotopically aligned vertical cells that also project to the ventral cochlear nucleus. Glycine-mediated inhibition onto fusiform cells results in decreased tone-evoked activity as intensity is increased at frequencies adjacent to characteristic frequency (CF). DCN output is thus shaped by glycinergic inhibition, which can be readily assessed in recordings from fusiform cells. Previous DCN studies suggest an age-related loss of markers for glycinergic neurotransmission. The present study postulated that response properties of aged fusiform cells would show a loss of inhibition, resembling conditions observed with glycine receptor blockade. The functional impact of aging was examined by comparing response properties from units meeting fusiform-cell criteria in young and aged rats. Fusiform cells in aged animals displayed significantly higher maximum discharge rates to CF tones than those recorded from young-adult animals. Fusiform cells of aged rats displayed significantly fewer nonmonotonic CF rate-level functions and an age-related change in temporal response properties. These findings are consistent with an age-related loss of glycinergic input, likely from vertical cells, and with findings from other sensory aging studies suggesting a selective age-related decrement in inhibitory amino acid neurotransmitter function. [ABSTRACT FROM AUTHOR]

Objectives: Tonsillectomy is one of the most commonly performed otolaryngologic procedures in the United States. Many options and controversies exist regarding techniques and peri-operative management. The purpose of the study was to examine current practice patterns among otolaryngologists regarding tonsillectomy. Methods: A 13 question survey regarding tonsillectomy techniques and peri-operative management was mailed to 10% of randomly selected board certified otolaryngologists of the AAO-HNS in the spring of 2002. Four hundred and eighteen anonymously completed questionnaires were returned, for a response rate of 58.5%. Statistical analysis of survey data was performed by means of cross tabulation and Pearson Chi-Square Calculation. Results: Monopolar electrocautery was the most common technique used among those surveyed (53.5%). There was a significant correlation between choice of monopolar electrocautery and the cited reason for choice of technique being decreased blood loss (P<0.001). There was no relationship between pediatric fellowship training and choice of technique. 97.7% routinely admitted sleep apnea patients for post-operative observation. There was no significant correlation between practice setting (tertiary versus community) and type of post-operative monitoring for sleep apnea patients, with patients most commonly admitted to an intermediate care setting. Conclusion: In our survey, the most common surgical technique for tonsillectomy was monopolar electrocautery, chosen for the reason of decreased blood loss. [Copyright &y& Elsevier]

This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of aminoglycoside (AG) ototoxicity. Two groups of five 250-350 g albino guinea pigs served as subjects. For 28 days, albino guinea pigs were administered either 200 rog/kg/day amikacin, or saline subcutaneously. Auditory brainstem response testing was performed prior to the first injection and again before sacrifice, 28 days later. Cochleae were harvested and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase activities and malondialdehyde levels were measured. All antioxidant enzymes had significantly lower activity in the amikacin group (p < 0.05) than in the control group. The difference in cochlear antioxidant enzyme activity between groups inversely correlated significantly with the change in ABR thresholds. The greatest correlation was for the high frequencies, which are most affected by aminoglycosides. This study demonstrates that antioxidant enzyme activity and amikacin-induced hearing loss significantly covary. [ABSTRACT FROM AUTHOR]

The inferior colliculus (IC) is an important auditory processing center receiving inputs from lower brainstem nuclei, higher auditory and nonauditory structures, and contralateral IC. The IC, along with other auditory structures, is involved in coding information about the envelope of complex signals. Biologically relevant acoustic signals, including animal vocalizations and speech, are spectrally and temporally complex and display amplitude and frequency variations over time. Certain IC neurons respond selectively over a narrow range of modulation frequencies to sinusoidally amplitude modulated (SAM) stimuli. Responses to SAM stimuli can be measured in terms of discharge rate, with rate plotted against the modulation frequency to generate rate modulation transfer functions (rMTF). A role for the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in shaping selective responses to SAM stimuli has been suggested. The present study examined the role of GABA in shaping responses to SAM stimuli in the IC of anesthetized chinchilla. Responses from 94 IC neurons were obtained before, during and after iontophoretic application of the GABAA receptor antagonist bicuculline methiodide. Complete responses to SAM stimuli were obtained from 55 extensively tested neurons, displaying band-pass (38) and low-pass rMTFs (17). For neurons showing band-pass rMTFs, GABAA receptor blockade selectively increased discharge rate at low modulation frequencies for 14 units, increased discharge near the best modulation frequency for 12 units. For neurons showing low-pass rMTFs, GABAA receptor blockade selectively increased discharge rate at low modulation frequencies for nine units. GABAA receptor blockade consistently reduced peak modulation gain, producing low-pass gain functions in a subset of IC neurons. In support of previous findings suggesting that selective temporal responses to SAM stimuli are coded in lower brainstem nuclei, temporal responses to SAM stimuli were relatively unaffected by GABAA receptor blockade. These findings support a role for GABA in shaping selective rate responses to SAM stimuli for a subset of chinchilla IC neurons. [Copyright &y& Elsevier]

The strategy of delaying or retarding the progression of Alzheimer's disease requires early diagnosis and treatment. Previous research indicates that measurement of changes in olfaction and cognition will play an important role in the early detection of AD and in the monitoring of therapy effectiveness. Using the data of 177 subjects, our objective was to study the measurement properties of the University of Pennsylvania Smell Identification Test (UPSIT) using a Rasch scaling framework. The results indicate that the UPSIT can yield a linear, unbiased, and unidimensional Rasch measure of human smell recognition abilities. As expected, olfactory recognition ability decreased with age, and at the rate of about 0.05 Logits per year. Also, Alzheimer's patients showed a decrease in smell recognition equivalent to that experienced by healthy subjects over the course of 30 years. Hormone replacement therapy was not found to affect healthy women's olfactory recognition ability. Additional diagnostic information can be extracted from the analysis of incorrect responses patterns that is relevant to group membership. [ABSTRACT FROM AUTHOR]

Here, we present results of quantum cascade laser lifetime tests under various aging conditions including an accelerated life test. The total accumulated life time exceeds 1.5 x 106 device hours. The longest single device aging time was 46500 hours without failure in the room temperature aging test. Four failures were found in a group of 19 devices subjected to the accelerated life test with a heat-sink temperature of 60 °C and a continuous-wave current of 1 A. Failure mode analyses revealed that thermally induced oxidation of InP in the semi-insulating layer is the cause of failure. An activation energy of 1.2 eV is derived from the dependence of the failure rate on laser core temperature. The mean time to failure of the quantum cascade lasers operating at a typical condition with the current density of 5 kA/cm² and heat-sink temperature of 25 °C is expected to be 809 000 hours. [ABSTRACT FROM AUTHOR]

Abstract: l-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that l-theanine has been shown to inhibit caffeine''s stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that l-theanine may suppress opioid withdrawal signs. Additionally, l-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties. Thus, in these studies we determined whether l-theanine attenuates opioid-withdrawal signs in morphine-dependent rhesus monkeys, a model for spontaneous opioid withdrawal in human opioid addicts. We also evaluated whether l-theanine decreases anxiety-like behavior in mice, using the elevated plus maze and marble burying assays. l-theanine significantly attenuated designated opioid withdrawal signs, including fighting, rigid abdominal muscles, vocalizing on palpation of abdomen, pacing, retching, wet-dog shakes, and masturbation. It had a relatively quick onset of action that persisted for at least 2.5h. l-theanine also produced anxiolytic-like effects in the elevated plus maze and the marble burying assay in naïve mice at doses that did not significantly affect motor behavior. The results of these studies suggest that l-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors. [Copyright &y& Elsevier]

MDAN-21, 7'-{2-[(7-{2-[({(5α,6α)-4,5-Epoxy-3,14-dihydroxy-17-methylmorphin-6-yl}-aminocarbonyl)metoxy]-acetylamino} -heptylaminocarbonyl)-methoxy]-acetylamino}-naltrindole, a bivalent opioid ligand containing a mu-opioid receptor agonist (derived from oxymorphone) linked to the delta-opioid receptor antagonist (related to naltrindole) by a spacer of 21 atoms, was reported to have potent analgesic properties in mice. Tolerance, physical dependence, and conditioned place preference were not evident in that species. The finding that bivalent ligands in this series, with spacers 19 atoms or greater, were devoid of tolerance and dependence led to the proposal that MDAN-21 targets heteromeric mu-delta-opioid receptors. The present study focused on its effects in nonhuman primates (Macaca mulatta), a species with a physiology and behavioral repertoire not unlike humans. With regard to opioids, this species usually better predicts clinical outcomes. MDAN-21 substituted for morphine in morphinedependent monkeys in the remarkably low dose range 0.006-0.032 mg/kg, subcutaneously. Although MDAN-21 failed to produce reliable thermal analgesia in the dose range 0.0032-0.032 mg/kg, intramuscularly, it was active in the same dose range and by the same route of administration, in the capsaicin-induced thermal allodynia assay. The results suggest that MDAN-21 may be useful in the treatment of opioid dependence and allodynia. The data provide additional evidence that opioid withdrawal is associated with sensitized pain. [ABSTRACT FROM AUTHOR]

Abstract: We have previously reported rescue from noise-induced auditory brainstem response (ABR) threshold shifts with d-methionine (d-met) administration 1 h after noise exposure. The present study investigated further d-met rescue intervals at 3, 5 and 7 h post-noise exposure. Chinchillas laniger were exposed to a 6 h 105 dB sound pressure level (dB SPL) octave band noise (OBN) and then administered d-met i.p. starting 3, 5, or 7 h after noise exposure; controls received saline i.p. immediately after noise exposure. ABR assessments were performed at baseline and on post-exposure days 1 and 21. Outer hair cell (OHC) loss was measured in cochleae obtained at sacrifice 21 days post-exposure. Administration of d-met starting at any of the delay times of 3–7 h post-noise exposure significantly reduced day 21 ABR threshold shift at 2 and 4 kHz and OHC loss at all hair cell regions measured (2, 4, 6 and 8 kHz). ABR threshold shifts in the control group at 6 and 8 kHz were only 8 and 11 dB respectively allowing little opportunity to observe protection at those 2 frequencies. [Copyright &y& Elsevier]

The article discusses research on the incidence and under-recognition of delirium in patients suffering from urinary disorders. The study involved 141 patient and found that 17 patients have delirium, with 6 of them having no record of delirium by physicians. It is noted that delirium may increase morbidity in patients, as well as medical costs.

Abstract: Aims: Our previous work revealed that mice lacking the p50 subunit of transcription factor nuclear factor kappa B (NF-κB) (p50 KO mice) and genetically intact F2 mice have similar locomotion under basal conditions, yet p50 KO mice show greater locomotor activation after caffeine ingestion. In this report, we test whether KO mice display altered caffeine pharmacokinetics or increased caffeine-induced DA turnover relative to F2 mice, and evaluate the impact of intraperitoneal administration of specific adenosine and DA receptor antagonists on locomotor activity. Main methods: Concentrations of DA and caffeine were measured using high performance liquid chromatography. DA turnover was measured after treatment of mice with an inhibitor of tyrosine hydroxylase. Locomotor activity was measured using telemetry. Key findings: The data reveal that 1) caffeine concentrations in blood and brain are similar in KO and F2 mice after oral or intraperitoneal administration; 2) KO mice show greater DA turnover under basal conditions, but turnover is similar in both strains after caffeine administration; 3) the specific A2AAR antagonist SCH 58261 induces greater locomotion in KO versus F2 mice; and 4) the activating effect of SCH 58261 in KO mice is prevented by prior treatment with the D2R antagonist raclopride. Significance: These findings support the conclusions that 1) A2AAR has a major impact on behavioral activation of p50 KO mice, and 2) D2R mediated neurotransmission is important to this effect. [Copyright &y& Elsevier]

Reduced insulin sensitivity and glucose intolerance have been long suspected of having important involvement in aging. Here we report that in studies of calorie restriction (CR) effects in mutant (Propldf and growth hormone receptor knockout [GHIRKO]) and normal mice, insulin sensitivity was strongly associated with longevity. Of particular interest was enhancement of the already increased insulin sensitivity in CR df/df mice in which longevity was also further extended and the lack of changes in insulin sensitivity in calorically restricted GHRKO mice in which there was no further increase in average life span. We suggest that enhanced insulin sensitivity, in conjunction with reduced insulin levels, may represent an important (although almost certainly not exclusive) mechanism of increased longevity in hypopituitary, growth hormone (GH)-resistant, and calorie-restricted animals. We also report that the effects of GH treatment on insulin sensitivity may be limited to the period of OH administration. [ABSTRACT FROM AUTHOR]

Integration of multimodal information is essential for understanding complex environments. In the auditory system, multisensory integration first occurs in the cochlear nucleus (CN), where auditory nerve and somatosensory pathways converge (Shore, 2005). A unique feature of multisensory neurons is their propensity to receive cross-modal compensation after deafening. Based on our findings that the vesicular glutamate transporters, VGLUT1 and VGLUT2, are differentially associated with auditory nerve and somatosensory inputs to the CN, respectively (Zhou et al., 2007), we examined their relative distributions after unilateral deafening. After unilateral intracochlear injections of kanamycin (1 and 2 weeks), VGLUT1 immunoreactivity (ir) in the magnocellular CN ipsilateral to the cochlear damage was significantly decreased, whereas VGLUT2-ir in regions that receive nonauditory input was significantly increased 2 weeks after deafening. The pathway-specific amplification of VGLUT2 expression in the CN suggests that, in compensatory response to deafening, the nonauditory influence on CN is significantly enhanced. One undesirable consequence of enhanced glutamatergic inputs could be the increased spontaneous rates in CN neurons that occur after hearing loss and that have been proposed as correlates of the phantom auditory sensations commonly called tinnitus. [ABSTRACT FROM AUTHOR]

Aging and acoustic trauma may result in partial peripheral deafferentation in the central auditory pathway of the mammalian brain. In accord with homeostatic plasticity, loss of sensory input results in a change in pre- and postsynaptic GABAergic and glycinergic inhibitory neurotransmission. As seen in development, age-related changes may be activity dependent. Age-related presynaptic changes in the cochlear nucleus include reduced glycine levels, while in the auditory midbrain and cortex, GABA synthesis and release are altered. Presumably, in response to age-related decreases in presynaptic release of inhibitory neurotransmitters, there are age-related postsynaptic subunit changes in the composition of the glycine (GlyR) and GABAA (GABAAR) receptors. Age-related changes in the subunit makeup of inhibitory pentameric receptor constructs result in altered pharmacological and physiological responses consistent with a net down-regulation of functional inhibition. Age-related functional changes associated with glycine neurotransmission in dorsal cochlear nucleus (DCN) include altered intensity and temporal coding by DCN projection neurons. Loss of synaptic inhibition in the superior olivary complex (SOC) and the inferior colliculus (IC) likely affect the ability of aged animals to localize sounds in their natural environment. Age-related postsynaptic GABAAR changes in IC and primary auditory cortex (Al) involve changes in the subunit makeup of GABAARs. In turn, these changes cause age-related changes in the pharmacology and response properties of neurons in IC and Al circuits, which collectively may affect temporal processing and response reliability. Findings of age-related inhibitory changes within mammalian auditory circuits are similar to age and deafferentation plasticity changes observed in other sensory systems. Although few studies have examined sensory aging in the wild, these age-related changes would likely compromise an animal's ability to avoid predation or to be a successful predator in their natural environment. [ABSTRACT FROM AUTHOR]

Abstract: The striatal dopamine D2 receptor (D2R) and adenosine A2A receptor (A2AAR) exhibit mutually antagonistic effects through physical interactions and by differential modulation of post-receptor signaling pathways. The expression of the A2AAR and the D2R is differentially regulated by nuclear factor-κB (NF-κB). In this report, we determined the role of NF-κB in regulation of these receptors by comparing mice deficient in the NF-κB p50 subunit (p50 KO) with genetically intact B6129PF2/J (F2) mice. Quantification of adenosine receptor (AR) subtypes in mouse striatum by real time PCR, immunocytochemistry and radioligand binding assays showed more A2AAR but less A1AR in p50 KO mice as compared with F2 mice. Striata from p50 KO mice also had less D2R mRNA and [3H]-methylspiperone binding than did striata from F2 mice. Gαolf and Gαs proteins, which are transducers of A2AAR signals, were also present at a higher level in striata from the p50 KO versus F2 mice. In contrast, the Gαi1 protein, which transduces signals from the A1AR and D2R, was significantly reduced in striata from p50 KO mice. Behaviorally, p50 KO mice exhibited increased locomotor activity relative to that of F2 mice after caffeine ingestion. These data are consistent with a role for the NF-κB in the regulation of A1AR, A2AAR, D2R and possibly their coupling G proteins in the striatum. Dysregulation of these receptors in the striata of p50 KO mice might sensitize these animals to locomotor stimulatory action of caffeine. [Copyright &y& Elsevier]

Abstract: A number of otoprotective agents are currently being investigated. Various types of agents have been found in animal studies to protect against hearing loss induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a decade we have been investigating d-methionine (d-met) as an otoprotective agent. Studies in our laboratory and others around the world have documented d-met’s otoprotective action, in a variety of species, against a variety of ototoxic insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced ototoxicity, protection of the stria vascularis has also been documented. Further d-met has an excellent safety profile. d-Met may act as both a direct and indirect antioxidant. In this report, we provide the results of three experiments, expanding findings in d-met protection in three of our translational research areas: protection from platinum based chemotherapy-, aminoglycoside- and noise-induced hearing loss. These experiments demonstrate oral d-met protection against cisplatin-induced ototoxicity, d-met protection against amikacin-induced ototoxicity, and d-met rescue from permanent noise-induced hearing loss when d-met is initiated 1h after noise exposure. These studies demonstrate some of the animal experiments needed as steps to translate a protective agent from bench to bedside. [Copyright &y& Elsevier]

The study describes a novel method for tinnitus screening in rats by use of gap detection reflex procedures. The authors hypothesized that if a background acoustic signal was qualitatively similar to the rat's tinnitus, poorer detection of a silent gap in the background would be expected, Rats with prior evidence of tinnitus at 10 kHz (n = 14) exhibited significantly worse gap detection than controls (n = 13) when the gap was embedded in a background similar to their tinnitus. No differences between tinnitus and control rats were found with 16 kHz or broadband noise backgrounds, which helped to rule out explanations related to hearing loss or general performance deficits. The results suggest that gap detection reflex procedures might be effective for rapid tinnitus screening in rats. [ABSTRACT FROM AUTHOR]

Abstract: Phosphorylcholine (PC) moieties were chemically attached to surfaces of polymer microparticles by addition of 2-methylacryloyloxyethyl phosphorylcholine monomer to the seeded, semi-continuous polymerisations of methyl methacrylate (MMA) and butyl acrylate (BA). The surface of the bio-functionalised polymer microparticles was principally characterised using X-ray photoelectron spectroscopy (XPS), dynamic nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), acoustophoresis and enzyme-linked immunosorbent assays (ELISA). It was found that the persulphate initiating species are concealed behind the phosphorylcholine containing monomer sequence located on the surface of the microparticles. The combination of analytical techniques showed that the surfaces of the polymer microparticles are extremely mobile above the glass transition temperature of the co-polymer and able to rearrange depending on the environment in which they are placed. This allows the phosphorylcholine moiety to be preferentially expressed at the surface in aqueous media, but not so in the dry state or conditions of ultra-high vacuum. In terms of the nature of the biocompatibility of phosphorylcholine containing polymers, no evidence was found for the irreversible structuring of water molecules around the phosphorylcholine moiety in the wet state. The results of this work suggest that a more likely contributory reason for the protein-resistant nature of phosphorylcholine containing polymers is the mobility of the phosphorylcholine moiety. Increases in biocompatibility correspond with increases in the hydrophilicity of a polymer surface when phosphorylcholine is preferentially expressed. A large free water fraction may be present in the phosphorylcholine containing monomer sequence, as part of a hydrogel structure located at the surface of the polymer microparticles. This, coupled with concomitant modification of the local electrical double-layer very close to the surface may also play a critical role in reducing protein–surface interactions. [Copyright &y& Elsevier]

Abstract: Zwitterionic surfactants based on phosphorylcholine and sulfobetaine have been used as emulsifiers to prepare stable, monodisperse copolymer latices of methyl methacrylate and butyl acrylate at high volume fractions using seeded semi-continuous emulsion copolymerisation. The amounts of these surfactants required when semi-continuously fed into the preparation are more than an order of magnitude less than is conventionally used. The low amounts of emulsifier used in successful polymerisations allowed subtle features of the mechanism of polymerisation for this system to be revealed. At specific surfactant concentrations in the polymerisations, the results suggested that the rate of incorporation of surfactant into the growing primary polymer particle was greater than the rate of addition. This led to primary particle instability and a coagulative mechanism being the dominant nucleation mechanism. This occurred at points at or just above the critical micelle concentration (CMC). The total number of particles formed was proportional to the concentration of surfactant to the 0.87–1.48 power and is consistent with Gilberts analysis on the coagulative nucleation mechanism. This suggests that at other surfactant concentrations above and below the CMC for each zwitterionic surfactant used, the presence of a classical homogenous or micellar nucleation mechanism, each coupled with a coagulative process could be present, although the experimental data presented are not conclusive. The surfactants were found to be crucial to the stability of the growing latex particle, but their mechanism of action is still unclear. The final polymer latex particles were electrostatically stabilised, at least in part, by the persulphate initiator fragments. [Copyright &y& Elsevier]

A generalized strategy is developed to predict the occurrence of a multicategory-multifactorial disease from a set of medical risk factors that are most often used to screen patients for the disease. The prediction problem is formulated as an M-class classification problem. The strategy employs fusion to combine risk factors into a single feature vector, normalization to fuse risk factors which have different formats and ranges, rank-sum ordering for feature selection, discrete Karhunen-Loeve transform-based transformation to facilitate parametric classifier development, and the design of parametric classifiers. Two methods, which differ on how the features are selected, are developed. In the first method, features are selected from a set consisting of linear combinations of all risk factors. In the second method, the features are linear combinations of a preselected subset of the risk factors. The methods are applied to predict the occurrence of Alzheimer's disease (AD) into three classes: Probable-AD, Possible-AD, and Uncertain. It is shown that a classification accuracy of over 71% can be obtained. This result is quite encouraging given that AD is very difficult to clinically diagnose. Higher classification accuracies can be expected for diseases that are not as complex to diagnose as AD. Most importantly, it is concluded that the generalized strategy can not only be applied to the multicategory-multifactorial disease prediction problem but also to other multiclass pattern recognition problems involving diverse information collected from different sources. [ABSTRACT FROM AUTHOR]