86 research outputs found

    Healthy Boundaries, Healthy Ministry

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    Maintaining the integrity of the pastoral relationship and protecting those who are vulnerable are two essential dimensions in the practice of ministry. In order to fulfill these goals, one must have healthy boundaries sustained by self-awareness, self-discipline, and accountability

    Telemetry Controlled Brain Machine Interface To Train Cortical Circuits

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    The goal of this dissertation is to document functional reorganization in rat primary somatosensory (SI) cortex. This work proposes to strengthen the interhemispheric connection between homotopic sites in forelimb barrel cortex (FBC) through intracortical microstimulation (ICMS) and induce functional reorganization whereby neurons in the FBC respond to new input from the ipsilateral forelimb. Furthermore, a wireless microstimulation and recording device was developed for producing enhancement and functional reorganization of cortical circuits in FBC. The goal of Experiment One was to test the hypothesis that layer V neurons projected to homotopic sites in contralateral layer V FBC. Retrograde or anterograde neuronal tracer injections were made to characterize the distribution of callosal projecting neurons in contralateral SI that terminate in layer VFBC and where layer V callosal projecting neurons terminate in contralateral SI. The results showed a differential pattern of interhemispheric connectivity between homotopic forelimb representations in layer V FBC. The goal of Experiment Two was to test the hypothesis that ICMS enhances the interhemispheric pathway and leads to functional reorganization. ICMS was delivered in vivo to the interhemispheric pathway between homotopic layer V barrel cortices and multiunit recordings were made to assess changes in firing rate. The results showed ICMS strengthens interhemispheric connectivity and leads to functional reorganization in rat FBC. The goal of Experiment Three was to develop an interactive telemetry-based neural interface device for the controlled delivery of ICMS and recording response activity in rodent. The device successfully delivered microstimulation to a single electrode in SIand recorded evoked responses from a separate electrode in contralateral SI. Its performance was shown to be comparable to commercial stimulating and recording systems. This system serves as a prototype of a wearable compact device. The data suggest that neurons in rat FBC can be induced to respond to new input from the ipsilateral forelimb by enhancing the interhemispheric pathway with ICMS. An interactive system for the controlled delivery of telemetry-based microstimulation and real-time recordings has been demonstrated in vivo. These studies provide the framework for subsequent studies of interhemispheric pathway enhancement and functional reorganization in freely moving rats

    Theology, News and Notes - Vol. 29, No. 02

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    Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1198/thumbnail.jp

    Modelling multi-scale state-switching functional data with hidden Markov models

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    Data sets comprised of sequences of curves sampled at high frequencies in time are increasingly common in practice, but they can exhibit complicated dependence structures that cannot be modelled using common methods of Functional Data Analysis (FDA). We detail a hierarchical approach which treats the curves as observations from a hidden Markov model (HMM). The distribution of each curve is then defined by another fine-scale model which may involve auto-regression and require data transformations using moving-window summary statistics or Fourier analysis. This approach is broadly applicable to sequences of curves exhibiting intricate dependence structures. As a case study, we use this framework to model the fine-scale kinematic movement of a northern resident killer whale (Orcinus orca) off the coast of British Columbia, Canada. Through simulations, we show that our model produces more interpretable state estimation and more accurate parameter estimates compared to existing methods.Comment: 23 pages, 8 figures, 2 tables. Supplementary material appended to submissio

    MODIFICATION OF THE BUILT ENVIRONMENT TO REDUCE ADOLESCENT E-CIGARETTE USE IN BURKE COUNTY, NC

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    Adolescent e-cigarette use in Burke County, NC, emerges as a critical social determinant of health (SDOH), significantly impacting the well-being of individuals aged 10 to 19. The built environment directly influences e-cigarette accessibility and acceptability. Addressing this multifaceted health concern requires collaborative efforts to comprehend and tackle the underlying factors. The proximity of tobacco retailers to schools underscores the necessity for collective action to regulate tobacco sales near educational institutions. Moreover, prevailing perceptions among Burke County adolescents regarding vaping's safety and prevalence emphasize the pressing demand for intervention. By implementing targeted regulations and education campaigns to impact e-cigarette availability, Burke County can foster healthier environments for its adolescents, addressing the intricate dynamics influencing adolescent e- cigarette use and ultimately promoting community well-being.Master of Public Healt

    Preoperative breast MRI and surgical outcomes in elderly women with invasive ductal and lobular carcinoma: a population-based study

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    Existing evidence suggests that preoperative breast magnetic resonance imaging (MRI) might not improve surgical outcomes in the general breast cancer population. To determine if patients differentially benefit from breast MRI, we examined surgical outcomes—initial mastectomy, reoperation, and final mastectomy rates—among patients grouped by histologic type

    A preliminary study on the induction of dioestrous ovulation in the mare – a possible method for inducing prolonged luteal phase

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    BACKGROUND: Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. METHODS: In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly in four mares (experimental group) in the luteal phase when a dioestrous follicle ≥ 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles ≥ 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. RESULTS: Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. CONCLUSION: HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle ≥ 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness

    A novel approach to investigate tissue-specific trinucleotide repeat instability

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    Abstract Background In Huntington's disease (HD), an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors. Results Here we describe a novel approach to gain insight into the factors responsible for the tissue specificity of somatic instability. Using accurate genetic knock-in mouse models of HD, we developed a reliable, high-throughput method to quantify tissue HD CAG repeat instability and integrated this with genome-wide bioinformatic approaches. Using tissue instability quantified in 16 tissues as a phenotype and tissue microarray gene expression as a predictor, we built a mathematical model and identified a gene expression signature that accurately predicted tissue instability. Using the predictive ability of this signature we found that somatic instability was not a consequence of pathogenesis. In support of this, genetic crosses with models of accelerated neuropathology failed to induce somatic instability. In addition, we searched for genes and pathways that correlated with tissue instability. We found that expression levels of DNA repair genes did not explain the tissue specificity of somatic instability. Instead, our data implicate other pathways, particularly cell cycle, metabolism and neurotransmitter pathways, acting in combination to generate tissue-specific patterns of instability. Conclusion Our study clearly demonstrates that multiple tissue factors reflect the level of somatic instability in different tissues. In addition, our quantitative, genome-wide approach is readily applicable to high-throughput assays and opens the door to widespread applications with the potential to accelerate the discovery of drugs that alter tissue instability

    Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort

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    © 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages

    Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

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    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
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