Browsing by Subject "Therapy"

Now showing 1 - 9 of 9
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    Deciding not to Un-Do the "I Do": a qualitative study of the therapy experiences of women who consider divorce but decide to remain married
    (2012-11) Kanewischer, Erica J.W.
    This preliminary study explores (1) women's experience of couple's therapy while they navigated decision-making around divorcing and (2) the role that the therapy played in the women's decision not to divorce. A phenomenological approach and qualitative method was used to gain a deeper understanding of the participant's therapeutic and decision-making experience. Women that considered initiating divorce before they turned 40 and attended at least five couple's therapy sessions (N = 15) were interviewed for this study. In general, participants reported that the therapy was helpful to them, their decision-making process and their marriages. Five main themes emerged from the interviews specifically regarding the interaction of considering divorce and couples therapy. They were: Women Initiated Therapy, Therapist Was Experienced as Neutral, Therapy was Helpful, Importance of Other Factors, and Gradual Process.
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    Defining a Neuroprotective Pathway for the Treatment of Ataxias
    (2016-08) Leathley, Emily
    Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia caused by neurodegeneration of specific cell types, namely Purkinje Cells (PCs) of the cerebellum. Mouse models of SCA Type 1 (SCA1) can be used to study the molecular mechanisms underlying PC degeneration and death. One SCA1 mouse model, ATXN1[30Q]D776, has an initial ataxia but no progressive degeneration or PC death. RNA-seq experiments identified the up-regulation in the cerebellum of the peptide hormone Cholecystokinin (Cck) in these mice. Knocking out Cck or the Cck1 receptor (Cck1R) in ATXN1[30Q]D776 mice confers a progressive disease where PC death occurs by thirty-six weeks of age. Weighted Gene Co-expression Network Analysis (WGCNA) performed on cerebellar RNA-seq data from ATXN1[30Q]D776;Cck-/- mice identified a disease progression-related gene set named the Pink Module that is influenced by Cck. A Cck1R agonist, A71623, was administered via osmotic minipump to ATXN1[30Q]D776;Cck-/- mice and AXTN1[82Q] mice, which are a more faithful representation of human SCA1 PC degeneration. In both mouse models, A71623 protected against progressive ataxia and PC degeneration. These results suggest that manipulation of the Cck-Cck1R pathway may be a therapeutic target for treatment of diseases involving PC degeneration.
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    Diagnosis and Management of Diabetes
    (2008-11-24) Solheid, Greg
    Aggressive use of glucose lowering agents to achieve HbA1c levels within normal (<6.0%) significantly increases risk of mortality in type 2 diabetics.
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    Engineering a CD19-Based Bispecific Molecule for CAR T Cell Therapy
    (2018-10) Schrack, Ian
    Cancer is a profoundly devastating disease both globally and within the United States. Current standards of care for treating cancer often includes surgical resection, chemotherapy, and radiation, each of which associates with its own set of adversities. An emerging class of treatment, immunotherapy, aims to utilize a patient’s own functional immune system as the therapeutic agent. Adoptive T cell therapy, but more specifically, chimeric antigen receptor (CAR) expressing T cell transfer, has had notable clinical success particularly against hematological malignancies. Chimeric antigen receptors are synthetic immunoreceptors which can redirect T cells towards varying tumor associated antigens, and, as a living cell, have the aptitude to develop sustainable memory and anti-tumor efficacy. However, conventional CAR T cells lack clinical modularity afforded by other treatments because, once transfused into a patient, the modified immune cell cannot be further altered. This nuance has resulted in several adverse side-effects which can be lethal to a subset of patients. Several resolutions have been posed to solve these reported complications, one of which is genetic encoding CAR specificity towards a secondary, bispecific molecule. This split-CAR approach has the propensity to improve antigen specificity, resolve antigen loss, afford dose-able T cell activation, and more. However, while many bispecific molecules have been developed, many lack both tunability and developability, both of which are important for the complexities and ever-changing nature of cancer. To meet this demand for engineered ligands, several high-throughput ligand selection methods have been developed for discovering ligands with a desired specificity. Furthermore, the associated CAR T cells may have poor aptitude for activation and expansion due to insufficient antigen availability. Conversely, conventional anti-CD19 CAR T cells can harness both healthy or malignant CD19-positive B cells for activation and expansion and thus have an abundance of available antigen. To these points, we utilized yeast-surface display and directed evolution as a pipeline for developing an CD19-based bispecific molecule capable of harnessing the proliferative aptitude of anti-CD19 CAR T cells to target antigens conventionally associated with solid tumors. Human CD19 was evolved for improved structural integrity through conformational selections using anti-CD19 monoclonal antibodies. Improved mutants were sequenced and provided input for designing a stably expressing, generation 2 CD19 library (termed Frame2). The second-generation diversity applied experimentally determined, beneficial mutations in multi-site fashion to drive the enhanced CD19 framework towards a higher stability and/or functionality. The Frame2 CD19 library was constructed as several fusion constructs containing either an anti-EGFR fibronectin domain or an anti-HER2 scFv in both N-terminal and C-terminal orientations and selectively evolved with anti-CD19 antibodies and the ligand-respective antigen. A set of functional bispecific CD19-ligand fusions were successfully developed. In theory, because the anti-CD19 antibodies used for fusion development have an identical binding domain to several anti-CD19 CAR constructs, these fusions should be detectable by CD19-targetted CAR T cells. Moreover, if the ligand domain also retains specificity, the CD19-ligand bispecific molecule should be capable of redirecting anti-CD19 CAR T cells to EGFR or HER2 expressing tumors.
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    Finding Home: A Qualitative Study on Healing Homelessness through Expressive Arts Engagement
    (2019-07) Bueno, José
    This phenomenological study seeks to expand the understanding of the impacts of expressive arts engagement on the mental health and trauma among homeless youth through the experiences of professionals working with those populations. Organizations across Massachusetts and Minnesota were selected based off their organizational mission statements for helping the homeless youth population, as well as referrals. This study demonstrates expressive arts engagement as one of the many tools in working through trauma and mental illness seen in the homeless youth population. Organizations should work towards the successful integration of the arts and healing mental illness found among youth homelessness.
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    HIFU Monitoring and control With dual-mode ultrasound arrays
    (2013-11) Casper, Andrew Jacob
    The biological effects of high-intensity focused ultrasound (HIFU) have been known and studied for decades. HIFU has been shown capable of treating a wide variety of diseases and disorders. However, despite its demonstrated potential, HIFU has been slow to gain clinical acceptance. This is due, in part, to the difficulty associated with robustly monitoring and controlling the delivery of the HIFU energy. The non-invasive nature of the surgery makes the assessment of treatment progression difficult, leading to long treatment times and a significant risk of under treatment. This thesis research develops new techniques and systems for robustly monitoring HIFU therapies for the safe and efficacious delivery of the intended treatment. Systems and algorithms were developed for the two most common modes of HIFU delivery systems: single-element and phased array applicators. Delivering HIFU with a single element transducer is a widely used technique in HIFU therapies. The simplicity of a single element offers many benefits in terms of cost and overall system complexity. Typical monitoring schemes rely on an external device (e.g. diagnostic ultrasound or MRI) to assess the progression of therapy. The research presented in this thesis explores using the same element to both deliver and monitor the HIFU therapy. The use of a dual-mode ultrasound transducer (DMUT) required the development of an FPGA based single-channel arbitrary waveform generator and high-speed data acquisition unit. Data collected from initial uncontrolled ablations led to the development of monitoring and control algorithms which were implemented directly on the FPGA. Close integration between the data acquisition and arbitrary waveform units allowed for fast, low latency control over the ablation process. Results are presented that demonstrate control of HIFU therapies over a broad range of intensities and in multiple in vitro tissues. The second area of investigation expands the DMUT research to an ultrasound phased-array. The phased-array allows for electronic steering of the HIFU focus and imaging of the acoustic medium. Investigating the dual-mode ultrasound array (DMUA) required the design and construction of a novel ultrasound-guided focused ultrasound (USgFUS) platform. The platform consisted of custom hardware designed for the unique requirements of operating a phased-array in both therapeutic and imaging modes. The platform also required the development of FPGA based signal processing and GPU based beamforming algorithms for online monitoring of the therapy process. The results presented in this thesis represent the first demonstration of a real-time USgFUS platform based around a DMUA. Experimental imaging and therapy results from series of animal experiments, including a 12 animal GLP study, are presented. In addition, in vitro control results, which build upon the DMUT work, are presented.
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    Hypoactive Sexual Desire
    (2009-05-06) Thomes, Jessica A.
    This Patient Education Tool addresses the symptoms, diagnosis and treatment for hypoactive sexual desire while raising awareness of patients to its commonality. Hopefully, this patient education tool will demonstrate to patients that there are alternatives to medications and that they should seek counsel in their doctor if they are having any type of concern about their sexual situation.
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    Regulation of Anti-Tumor Immunity and Immunotherapy Response In Colorectal Cancer
    (2020-06) Zhao, Xianda
    Immune checkpoint blockade therapy (ICBT) has revolutionized the treatment and management of numerous cancers, yet a substantial proportion of colorectal cancer (CRC) patients are resistant. Most importantly, the mechanisms that cause ICBT resistance in CRC patients are mostly unclear. Both clinical and laboratory studies implied that both tumor cell-intrinsic factors and traditional cancer therapies (e.g., chemotherapy and oncogenic pathway-targeted therapy) have regulatory effects on anti-tumor immunity and ICBT efficacy. In the present thesis, we first characterized the pathological and immunological features of different pre-clinical CRC models. We reported the feasibility of using small animal endoscopy to establish mouse orthotopic colon tumors. We found that tumors grown orthotopically in the colon microenvironment develop better immune infiltration than tumors with the same genetic background growing in a subcutaneous microenvironment. These data indicated that the tissue microenvironment impacts anti-tumor immunity. Meanwhile, we observed that the endoscopy-guided cancer cell line-originated orthotopic CRC model is much more sensitive to ICBT over the subcutaneous model, making it not suitable for experiments that require ICBT-resistant tumors. This observation made us decide to use the subcutaneous tumor models, which are ICBT-resistant, for understanding cancer immunotherapy resistance. In the second section, we evaluated the impact of tumor-draining lymph nodes (TdLNs) and chemotherapy on ICBT efficacy. Specifically, we demonstrated TdLNs are critical for tumor antigen-specific T-cell response in early-stage tumors. However, TdLNs shift from an immunoreactive to an immunotolerant environment during tumor development. In mice with advanced primary tumors, TdLNs are not the major reservoir of tumor antigen-specific T cells. To evaluate the impacts of those immunotolerant TdLNs on ICBT response, we established a surgical model to mimic tumor recurrence in situ. We surgically removed the established primary tumors with or without concurrent TdLNs resection. Then, we inoculated secondary tumors, which are in the same lymphatic drainage area as the primary tumors, to mimic tumor recurrency. Notably, removing those immunotolerant TdLNs concurrently with established primary tumors did not affect the ICBT response on localized secondary tumors. In another set of experiments, we evaluated the impacts of chemotherapy (5-FU) on ICBT efficacy. We revealed that using 5-FU as induction treatment for ICBT increased tumor visibility to immune cells, decreased immunosuppressive cells in the tumor microenvironment, and limited chemotherapy-induced T-cell depletion. However, sustained chemotherapy impaired the efficacy of ICBT by suppressing the host immune system and depleting tumor-infiltrating T cells. Therefore, the sequential combination of chemotherapy with ICBT may result in a better response than the sustained chemotherapy and ICBT combination. Finally, we investigated how tumor cells regulate T-cell activation via intercellular communication based on extracellular vesicles (EVs). Specifically, we revealed that tumor cells-secreted EVs (TEVs) containing microRNA miR-424 suppressed the CD28-CD80/86 costimulatory pathway in tumor-infiltrating T cells and dendritic cells. Modified TEVs with miR-424 knocked down enhanced T-cell mediated antitumor immune response in CRC tumor models and increased the response to ICBT. Intravenous injection of modified TEVs induced tumor antigen-specific immune responses. Moreover, injections of modified TEVs boosted the ICBT efficacy in CRC models that mimic treatment-refractory late-stage disease. Collectively, the present study improves our understanding of CRC anti-tumor immune regulation and proposed novel treatment for ICBT resistant human CRC.
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    Skilled Nursing Facility Use Under Hospital Controlled Bundled Payments
    (2019-11) Weissblum, Lianna
    Hospitals increasingly bear financial risk for health care spending after hospital discharge through payment reforms such as bundled payments and accountable care organizations. Under Model 2 of Medicare’s Bundled Payments for Care Improvement (BPCI) initiative, hospitals took on financial responsibility for health care use during an episode of care beginning at hospital admission and lasting up to 90 days after discharge. The financial success of Model 2 participants hinged on managing post-acute care use, including skilled nursing facility (SNFs) care. During BPCI, the primary drivers of SNF Medicare spending were length of stay and therapy intensity, which determined daily payment rates. SNF therapy intensity increased considerably in recent years, despite no significant changes in SNF patient frailty or outcomes. Reducing unnecessary overuse of SNF therapy would have lowered Medicare spending without decreasing quality of care. The objective of this study is to assess changes in SNF treatment intensity (length of stay, therapy intensity, payments) under BPCI Model 2, as well as changes in SNF referral patterns and the impact of SNF market power. I focus on lower extremity joint replacement (LEJR) episodes and compare the impact of Model 2 in a cohort of hospital participants that took on risk before it was mandatory (early adopters) to a cohort of hospitals that took on risk when it was mandatory (late adopters). I find that Model 2 hospital participation was associated with differential reductions in SNF use. During both early adopter and late adopter episodes, I found differential reductions in SNF days and Medicare payments. SNF therapy intensity declined for early adopter episodes only. Within SNF changes drove reductions in SNF length of stay and Medicare payments. However, SNF therapy intensity reductions in the early adopter population were driven by changes in SNF referral patterns. I find limited evidence for large changes in referral concentration or historical SNF quality and efficiency under BPCI Model 2 across both early and late adopter hospitals. In terms of the impact of SNF market power, I find that SNF treatment intensity reductions were greatest in SNF markets with the greatest excess capacity and competition when using counties to define markets across both the early and late adopter cohorts. However, differences were not typically significant due to low statistical power. Based on the results of a power analysis, more hospital participants, may be required to detect statistically significant differences, particularly when stratifying participants into groups. Alternative results using health service areas (HSAs) to define SNF markets were less conclusive.