347 research outputs found

    The Effect of Music Therapy on the Maladpative Emotionally Regulative Behaviors of Adults with Developmental Disabilities

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    ABSTRACT The purpose of this study was to examine the effectiveness of individualized music therapy protocols in decreasing the duration of instances of elevated levels of maladaptive emotionally regulative behaviors in adults with developmental disabilities. The participants were four adults with developmental disabilities, recommended for the study based on the presence of severe and/or frequent instances of maladaptive emotionally regulative behaviors. ABAB reversal design was used to examine the effectiveness of the usual staff techniques (A) and the individualized music therapy protocols (B) in decreasing the duration of instances of maladaptive emotionally regulative behaviors. The independent variables were the following two conditions: interacting with each participant while he or she was exhibiting the targeted maladaptive emotionally regulative behaviors at a rate per minute that exceeded the participant's usual rate per minute, using (A) non-music interventions recommended by staff, or (B) individualized music therapy protocols. The dependent variable was the time that elapsed from the onset to the conclusion of each instance of elevated levels of maladaptive emotionally regulative behaviors. Results from the four case studies indicated that music therapy protocols can be used to decrease the duration of instances of elevated levels of maladaptive emotionally regulative behaviors in adults with developmental disabilities, and that music therapy protocols can decrease these behaviors more quickly than the usual staff techniques in most cases. Three out of four participants responded better to the music therapy protocols than the usual staff techniques. The final participant responded to music therapy protocols and staff techniques exactly the same in terms of average duration of instances of elevated levels of maladaptive emotionally regulative behaviors

    The Role of Faculty Learning Communities in Supporting Team-Based Learning

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    In this paper, the authors describe the faculty development initiatives and the role of faculty learning communities (FLCs) in supporting Team-Based Learning (TBL) at a large, research-intensive university. A systematic review of the initiatives found FLCs provided crucial support for both new and seasoned TBL practitioners and fostered connections between members, resulting in a need to give back to the community through mentorship. Results also showed members were eager to share their knowledge with the larger community and further research into TBL though scholarship, supporting the sustainability of the TBL community and further development of members\u27 teaching and scholarly practice

    Simulation of the White Dwarf -- White Dwarf galactic background in the LISA data

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    LISA (Laser Interferometer Space Antenna) is a proposed space mission, which will use coherent laser beams exchanged between three remote spacecraft to detect and study low-frequency cosmic gravitational radiation. In the low-part of its frequency band, the LISA strain sensitivity will be dominated by the incoherent superposition of hundreds of millions of gravitational wave signals radiated by inspiraling white-dwarf binaries present in our own galaxy. In order to estimate the magnitude of the LISA response to this background, we have simulated a synthesized population that recently appeared in the literature. We find the amplitude of the galactic white-dwarf binary background in the LISA data to be modulated in time, reaching a minimum equal to about twice that of the LISA noise for a period of about two months around the time when the Sun-LISA direction is roughly oriented towards the Autumn equinox. Since the galactic white-dwarfs background will be observed by LISA not as a stationary but rather as a cyclostationary random process with a period of one year, we summarize the theory of cyclostationary random processes and present the corresponding generalized spectral method needed to characterize such process. We find that, by measuring the generalized spectral components of the white-dwarf background, LISA will be able to infer properties of the distribution of the white-dwarfs binary systems present in our Galaxy.Comment: 14 pages and 6 figures. Submitted to Classical and Quantum Gravity (Proceedings of GWDAW9

    Non-unions treated with bone morphogenic protein 7: introducing the quantitative measurement of human serum cytokine levels as promising tool in evaluation of adjunct non-union therapy

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    Background: In this study we sought to determine if application of bone morphogenic protein 7 (BMP-7) promotes physiological bone healing of non-unions and to investigate if serum cytokine analysis may serve as a promising tool in the analysis of adjunct non-union therapy. Therefore we analyzed the influence of BMP-7 application on the serum cytokine expression patterns on patients with impaired bone healing compared to patients that showed proper bone healing. Methods: Our study involved analyzing blood samples from 208 patients with long bone fractures together with patients that subsequently developed non-unions. From this large pool, 15 patients with atrophic non-union were matched to 15 patients with atrophic non-union treated with local application of BMP-7 as well as normal bone healing. Changes in the cytokine expression patterns were monitored during the 1st, 2nd, 4th, 8th, 12th and 52nd week. The patients were followed both clinically and radiologically for the entire duration of the study. Serum cytokine expression levels of transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were analyzed and compared. Results: Serum expression of TGF-β were nearly parallel in all three groups, however serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). bFGF serum concentrations increased initially in patients with proper bone healing and in those treated with BMP-7. Afterwards, values decreased; bFGF serum concentrations in the BMP-7 group were significantly higher than in the other groups (p < 0.05). PDGF serum concentration levels were nearly parallel in all groups, serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). Conclusion: Treatment with BMP-7 in patients with former non-unions led to similar cytokine expression patterns after treatment as those found in patients with proper bone healing. Our results suggest that treatment with BMP-7 promote healing of non-unions. Furthermore, quantitative measurement of serum cytokine expression is a promising tool for evaluating the effectiveness of additional non-union therapies such as adjunct application of growth factors

    The Structural Basis of Peptide Binding at Class A G Protein-Coupled Receptors

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    G protein-coupled receptors (GPCRs) represent the largest membrane protein family and a significant target class for therapeutics. Receptors from GPCRs’ largest class, class A, influence virtually every aspect of human physiology. About 45% of the members of this family endogenously bind flexible peptides or peptides segments within larger protein ligands. While many of these peptides have been structurally characterized in their solution state, the few studies of peptides in their receptor-bound state suggest that these peptides interact with a shared set of residues and undergo significant conformational changes. For the purpose of understanding binding dynamics and the development of peptidomimetic drug compounds, further studies should investigate the peptide ligands that are complexed to their cognate receptor

    Cln5 represents a new type of cysteine-based S-depalmitoylase linked to neurodegeneration

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    Genetic CLN5 variants are associated with childhood neurodegeneration and Alzheimer’s disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (S-depalmitoylation) activity using fluorescent substrates. Mutational analysis revealed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for Cln5 thioesterase activity, uncovering a new cysteine-based catalytic mechanism for S-depalmitoylation enzymes. Last, we found that Cln5-deficient neuronal progenitor cells showed reduced thioesterase activity, confirming live cell function of Cln5 in setting S-depalmitoylation levels. Our results provide new insight into the function of Cln5, emphasize the importance of S-depalmitoylation in neuronal homeostasis, and disclose a new, unexpected enzymatic function for the N1pC/P60 superfamily of proteins

    "Tue Gutes und rede darüber" : Corporate Social Responsibility fördert das Image und sichert Ressourcen – und was bringt es den Mitarbeitern und der Gesellschaft?

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    Erfolgreiche Unternehmer wie SAP-Mitbegründer Dietmar Hopp oder Microsoft-Gründer Bill Gates sind Pioniere von Corporate Social Responsibility (CSR). Regelmäßig erichten die Medien über ihre vielfältigen sozialen Aktivitäten und animieren damit andere Unternehmen, sich in ähnlicher Weise zu engagieren. Welche Motive stecken dahinter? Wollen diese Firmen etwas Gutes für die Gesellschaft tun oder bestimmen Strategien, die von negativen Folgen kapitalistischen Handelns ablenken sollen, ihr altruistisches Handeln? Fußen betriebliche Maßnahmen zur Vereinbarkeit von Beruf und Familie auf sozialem Engagement, oder macht der demografi sche Wandel die verstärkte Integration von Frauen erst notwendig

    Theologie

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    Die Theologie beschäftigt sich mit keiner anderen Welt als die Umwelt(natur)wissenschaften. Sie versteht die Welt jedoch nicht aus sich heraus, sondern als Teil eines Relationsgefüges. Dabei thematisiert sie das komplexe Verhältnis von Mensch und Natur im Kontext seiner religiösen Deutungen. Eine Sakralisierung oder Divinisierung der Natur oder des Lebens wird dabei ebenso problematisiert wie ein materialistischer Reduktionismus. Während die bibelwissenschaftliche und historische Theologie religiöse Deutungsmuster von „Natur“ in ihrem historischen Kontext analysiert, bezieht die systematische Theologie Fragen gegenwärtiger Welt- und Naturverhältnisse in den Forschungsdiskurs ein. Theologische Umweltethik bedenkt religiöse, kulturelle und ethische Aspekte menschlicher Lebensführung. Hier setzt sie sich insbesondere mit der engen Korrelation von sozialen und ökologischen Aspekten sowie mit Freiheit, Verantwortung und Handlungsfähigkeit unter Endlichkeitsbedingungen und angesichts bedrohlicher Zukunftsszenarien auseinander

    Clinical implementation of an algorithm for predicting exacerbations in patients with COPD in telemonitoring:a study protocol for a single-blinded randomized controlled trial

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    BACKGROUND: Acute exacerbations have a significant impact on patients with COPD by accelerating the decline in lung function leading to decreased health-related quality of life and survival time. In telehealth, health care professionals exercise clinical judgment over a physical distance. Telehealth has been implemented as a way to monitor patients more closely in daily life with an intention to intervene earlier when physical measurements indicate that health deteriorates. Several studies call for research investigating the ability of telehealth to automatically flag risk of exacerbations by applying the physical measurements that are collected as part of the monitoring routines to support health care professionals. However, more research is needed to further develop, test, and validate prediction algorithms to ensure that these algorithms improve outcomes before they are widely implemented in practice. METHOD: This trial tests a COPD prediction algorithm that is integrated into an existing telehealth system, which has been developed from the previous Danish large-scale trial, TeleCare North (NCT: 01984840). The COPD prediction algorithm aims to support clinical decisions by predicting the risk of exacerbations for patients with COPD based on selected physiological parameters. A prospective, parallel two-armed randomized controlled trial with approximately 200 participants with COPD will be conducted. The participants live in Aalborg municipality, which is located in the North Denmark Region. All participants are familiar with the telehealth system in advance. In addition to the participants’ usual weekly monitored measurements, they are asked to measure their oxygen saturation two more times a week during the trial period. The primary outcome is the number of exacerbations defined as an acute hospitalization from baseline to follow-up. Secondary outcomes include changes in health-related quality of life measured by both the 12-Item Short Form Survey version 2 and EuroQol-5 Dimension Questionnaire as well as the incremental cost-effectiveness ratio. DISCUSSION: This trial seeks to explore whether the COPD prediction algorithm has the potential to support early detection of exacerbations in a telehealth setting. The COPD prediction algorithm may initiate timely treatment, which may decrease the number of hospitalizations. TRIAL REGISTRATION: NCT05218525 (pending at clinicaltrials.gov) (date, month, year

    Understanding Cytotoxicity and Cytostaticity in a High-Throughput Screening Collection.

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    While mechanisms of cytotoxicity and cytostaticity have been studied extensively from the biological side, relatively little is currently understood regarding areas of chemical space leading to cytotoxicity and cytostasis in large compound collections. Predicting and rationalizing potential adverse mechanism-of-actions (MoAs) of small molecules is however crucial for screening library design, given the link of even low level cytotoxicity and adverse events observed in man. In this study, we analyzed results from a cell-based cytotoxicity screening cascade, comprising 296 970 nontoxic, 5784 cytotoxic and cytostatic, and 2327 cytostatic-only compounds evaluated on the THP-1 cell-line. We employed an in silico MoA analysis protocol, utilizing 9.5 million active and 602 million inactive bioactivity points to generate target predictions, annotate predicted targets with pathways, and calculate enrichment metrics to highlight targets and pathways. Predictions identify known mechanisms for the top ranking targets and pathways for both phenotypes after review and indicate that while processes involved in cytotoxicity versus cytostaticity seem to overlap, differences between both phenotypes seem to exist to some extent. Cytotoxic predictions highlight many kinases, including the potentially novel cytotoxicity-related target STK32C, while cytostatic predictions outline targets linked with response to DNA damage, metabolism, and cytoskeletal machinery. Fragment analysis was also employed to generate a library of toxicophores to improve general understanding of the chemical features driving toxicity. We highlight substructures with potential kinase-dependent and kinase-independent mechanisms of toxicity. We also trained a cytotoxic classification model on proprietary and public compound readouts, and prospectively validated these on 988 novel compounds comprising difficult and trivial testing instances, to establish the applicability domain of models. The proprietary model performed with precision and recall scores of 77.9% and 83.8%, respectively. The MoA results and top ranking substructures with accompanying MoA predictions are available as a platform to assess screening collections.Biotechnology and Biological Sciences Research Council, AstraZenec
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