2,295 research outputs found

    Transmural differences in the properties of ventricular muscle in normal and failing rabbit hearts

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    It is now well established that electrical, metabolic and mechanical properties vary across the wall of the mammalian ventricle. In this thesis, protein expression, intracellular [Ca2+], and myocyte shortening are examined in myocardium from endocardial and epicardial regions of normal rabbit hearts. These properties were compared with those in equivalent regions of hearts with significant left ventricular dysfunction (LVD) resulting from a ventricular apical infarct. Resting myocyte length was significantly longer in myocytes isolated from LVD hearts but no regional differences in resting myocyte length in sham or LVD myocytes was observed. Fractional shortening was not significantly different between endocardial and epicardial myocytes from both sham and LVD hearts. LVD endocardial myocytes shortened less than myocytes from the comparable region in the sham group. No difference in fractional shortening was observed when comparing epicardial myocytes from sham and LVD hearts. Contraction kinetics were slower in both LVD endocardial and epicardial myocytes. The rest decay effect was more pronounced in endocardial compared with epicardial myocytes in both sham and LVD groups but minimal differences were observed when comparing experimental groups. Peak systolic [Ca2+]i was similar in endocardial myocytes from both experimental groups but was significantly lower in the LVD epicardial group than sham. Peak systolic [Ca2+]i was similar between endocardial and epicardial myocytes in the sham group but LVD epicardial peak systolic [Ca2+]i was lower than endocardial. These results suggest various changes in [Ca2+]i transient amplitude and myocyte shortening in LVD that may be explained by changes in myofilament Ca2+ sensitivity. Transmural protein expression of Calsequestrin, SR Ca2+-ATPase (SERCA) and Na+/Ca2+ exchanger was similar in sham and LVD myocytes. Calsequestrin and Na+Ca2+ exchanger protein expression was significantly increased, and SERCA protein expression was significantly decreased, in LVD myocytes. The link between altered protein expression and altered intracellular [Ca2+] transients in LVD is discussed. Comparison of the amount of protein retrieved from sham and LVD ventricular homogenate samples showed that protein retrieval was similar throughout a range of ventricular tissue wet weights (60 to 1000mg) and in sham and LVD myocardial samples. In contrast, protein retrieved from crude SR preparations (250 - 1000mg) was significantly greater in LVD preparations than sham samples. In addition, crude SR vesicles derived from ventricular samples weighting less than 250mg proved unsuitable for experimental use because of the variable protein retrieval when using such small sample weights. Sources of experimental variation within the Western Blotting technique were also investigated. It was concluded that the major sources of variation were attributable to the electroblotting and the antibody binding steps

    Scenario planning and strategizing: an integrated approach

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    This thesis presents an analysis of how one UK Regional Development Agency (RDA) used scenario planning in its construction of the region’s Regional Economic Strategy (RES). Strategists are broadly defined to include those within the RDA charged with developing and enacting a consultative strategy making process, the consultants engaged to provide advice and expertise to ensure workshops were conducted effectively, and, individuals representing stakeholder organizations that attended these workshops and responded to written consultations. Four scenarios depicting the region in the year 2020 were produced, which were subsequently presented as an evidence-base for the strategy process. A draft RES was created and issued for consultation. Previous RES development processes had been criticized for their lack of consultation, in this iteration strategists skilfully utilized a recognized strategy making practice as a means of responding to this. The scenario planning approach they adopted bore little resemblance to to the sanitised and context-free recipes commonly presented in the strategy textbooks. The research is a reflective, longitudinal study with data drawn from forty-six semi-structured interviews producing an authentic rich description that illustrates how actors enacted a strategizing process in the complex environment of the UK public sector. The analysis highlights how the strategists were influenced by sometimes conflicting desires and aspirations, and that to reconcile these and ensure deadlines were met inductive, interpretive and subjective acts were required. This analysis presents strategists as bricoleurs, with the documents and draft strategies produced being socially situated co-constructions emerging from negotiated, temporally-bound, power-laden and politically-infused interactions

    Electroencephalography reflects the activity of sub-cortical brain regions during approach-withdrawal behaviour while listening to music

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    The ability of music to evoke activity changes in the core brain structures that underlie the experience of emotion suggests that it has the potential to be used in therapies for emotion disorders. A large volume of research has identified a network of sub-cortical brain regions underlying music-induced emotions. Additionally, separate evidence from electroencephalography (EEG) studies suggests that prefrontal asymmetry in the EEG reflects the approach-withdrawal response to music-induced emotion. However, fMRI and EEG measure quite different brain processes and we do not have a detailed understanding of the functional relationships between them in relation to music-induced emotion. We employ a joint EEG – fMRI paradigm to explore how EEG-based neural correlates of the approach-withdrawal response to music reflect activity changes in the sub-cortical emotional response network. The neural correlates examined are asymmetry in the prefrontal EEG, and the degree of disorder in that asymmetry over time, as measured by entropy. Participants’ EEG and fMRI were recorded simultaneously while the participants listened to music that had been specifically generated to target the elicitation of a wide range of affective states. While listening to this music, participants also continuously reported their felt affective states. Here we report on co-variations in the dynamics of these self-reports, the EEG, and the sub-cortical brain activity. We find that a set of sub-cortical brain regions in the emotional response network exhibits activity that significantly relates to prefrontal EEG asymmetry. Specifically, EEG in the pre-frontal cortex reflects not only cortical activity, but also changes in activity in the amygdala, posterior temporal cortex, and cerebellum. We also find that, while the magnitude of the asymmetry reflects activity in parts of the limbic and paralimbic systems, the entropy of that asymmetry reflects activity in parts of the autonomic response network such as the auditory cortex. This suggests that asymmetry magnitude reflects affective responses to music, while asymmetry entropy reflects autonomic responses to music. Thus, we demonstrate that it is possible to infer activity in the limbic and paralimbic systems from pre-frontal EEG asymmetry. These results show how EEG can be used to measure and monitor changes in the limbic and paralimbic systems. Specifically, they suggest that EEG asymmetry acts as an indicator of sub-cortical changes in activity induced by music. This shows that EEG may be used as a measure of the effectiveness of music therapy to evoke changes in activity in the sub-cortical emotion response network. This is also the first time that the activity of sub-cortical regions, normally considered “invisible” to EEG, has been shown to be characterisable directly from EEG dynamics measured during music listening

    Affective calibration of musical feature sets in an emotionally intelligent music composition system

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    Affectively driven algorithmic composition (AAC) is a rapidly growing field that exploits computer-aided composition in order to generate new music with particular emotional qualities or affective intentions. An AAC system was devised in order to generate a stimulus set covering nine discrete sectors of a two-dimensional emotion space by means of a 16-channel feed-forward artificial neural network. This system was used to generate a stimulus set of short pieces of music, which were rendered using a sampled piano timbre and evaluated by a group of experienced listeners who ascribed a two-dimensional valence-arousal coordinate to each stimulus. The underlying musical feature set, initially drawn from the literature, was subsequently adjusted by amplifying or attenuating the quantity of each feature in order to maximize the spread of stimuli in the valence-arousal space before a second listener evaluation was conducted. This process was repeated a third time in order to maximize the spread of valence-arousal coordinates ascribed to the generated stimulus set in comparison to a spread taken from an existing prerated database of stimuli, demonstrating that this prototype AAC system is capable of creating short sequences of music with a slight improvement on the range of emotion found in a stimulus set comprised of real-world, traditionally composed musical excerpts

    Getting to more effective weight management in antipsychotic-treated youth: a survey of barriers and preferences

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    Background: Mentally ill youth are at risk for developing obesity, especially when they require antipsychotic treatment; moreover, they may face unique challenges in adhering to behavioral weight loss interventions. The aims of this project were to characterize the challenges families of youth with psychiatric disorders face when engaging in weight loss treatment and to gather information on attitudes and preferences for weight management interventions in this population. Methods: We devised a telephone survey to evaluate caregiver-perceived barriers/challenges to and preferences for behavioral weight loss treatment in overweight or obese mentally ill youth ages 6–18 treated with an antipsychotic agent in an outpatient setting. Results: A total of 26 parents or primary caregivers completed the survey. The most commonly cited barriers to participation in physical activity (PA) and maintaining a healthy diet were child's dislike of PA and child's preference for energy-dense foods, respectively, which were impacted by psychiatric symptoms. Preferences for weight loss treatment included individualized, prescribed meal plans and shopping lists, and exercise support/demonstration, with a preference for Internet or cell phone applications to help with monitoring food intake and exercise. Conclusions: These results suggest that targets for obesity treatment in this population include individualized, specific support that takes into account the child's motivation, which is effected by psychiatric symptoms. Tools for providing support may include the use of telehealth visits and mobile device applications for self-monitoring

    Tailoring Organic-Organic Poly(vinylpyrrolidone) Microparticles and Fibers with Multiwalled Carbon Nanotubes for Reinforced Composites

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    Polymeric-based microparticles and fibers are tailorable for a wide range of common industrial and biomedical applications, while multiwalled carbon nanotubes (MWCNTs) are among the most useful macromolecules based on their outstanding electronic, mechanical, and optical properties at the nanoscale. If one combines these nanostructures with various polymeric precursors, their range of potential applications becomes even greater. One of the simplest and most affordable methods for fabricating micro- and nanostructures is electrospinning. Herein we demonstrate how MWCNTs may be used to produce tailor-made organic-organic poly(vinylpyrrolidone) (PVP) microparticles and fibers via electrospinning by studying their structural, vibrational, rheological, and mechanical properties' dependence on their solvent (ethanol (EtOH) or dimethylformamide (DMF)) and resulting morphology. Specifically, we find clear differences in morphologies from perfectly spherical and isolated microparticles to fibers mats, or a combination of fibers with entangled beads, with solvent type and concentration. On the basis of our findings, we propose that the mechanism governing the shape and size of the particles is a competition between the solvent's surface tension, dielectric constant, and viscoelastic properties. We show, based on both our experimental results and density functional theory (DFT) calculations, that OH functionalization of the MWCNTs is essential for achieving high PVP coverages and promoting the stability of the resulting PVP/MWCNT nanocomposite. Finally, by fabricating PVP/MWCNT fiber mats, we demonstrate that low concentrations (0.01-0.1 wt %) of MWCNTs led to a qualitative improvement (â250%) in the resulting mechanical properties, i.e., a reinforced composite. These results show how by controlling the solvent's dielectric constant, surface tension, and polymer concentration, one may produce tailor-made polymeric nanomaterials in combination with other organic/inorganic nanoparticles, i.e., silver, gold, or carbon allotropes, for next-generation applications
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