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The Resilience Songwriting Program for Adolescent Bereavement: A Mixed Methods Exploratory Study
No full textMusic therapy research with youth who are grieving frequently uses a combination of approaches (e.g., lyric analysis, improvisation, songwriting), but it is unclear to what extent each approach contributes to the treatment outcomes. The ability to interpret and apply this research is further limited by the lack of theory-driven music therapy interventions. The purpose of this exploratory study was to evaluate the impact of an 8-session, resilience-focused group songwriting program on protective factors in adolescents who are grieving and understand how they experienced the program. This study employed a single-group, pre-/post-test convergent mixed methods design. Participants included 10 adolescents experiencing bereavement (5 girls, 5 boys), ages 12 to 17 years. We implemented the program at a behavioral health clinic, a pediatric hospital bereavement support program, and a school. Quantitative outcomes measured were grief, coping, emotional expression, self-esteem, and meaning making. Qualitative data were captured through the use of semi-structured interviews after the program and in-session journaling. While not statistically significant, median scores for grief, coping, and meaning making improved from pre-test to post-test. No changes were found for self-esteem and only minimal improvements in emotional expression and coping. Qualitative findings suggested that the program offered adolescents a sense of togetherness and belonging, a way to safely express their grief-related emotions and experiences verbally and non-verbally, and opportunities for strengthening their musical and coping skills. These findings suggest that engaging in therapeutic songwriting alongside grieving peers may decrease levels of grief and enhance coping skills, meaning making, and social support.Ph.D., Creatve Arts in Therapy -- Drexel University, 201
Novel Biomimetic Proteoglycans for Molecular Engineering of the Urethra for Treatment of Stress Urinary Incontinence
No full textStress urinary incontinence (SUI), which affects approximately 56% of postmenopausal women, is the involuntary leakage of urine through urethra during physical activity. SUI is associated with a decrease in compliance and volume of urethral tissue, which is likely linked to a reduced proteoglycan:collagen ratio in the extracellular matrix (ECM). This thesis work examines the molecularly engineering of the urethra by injecting a novel family of biomimetic proteoglycans (BPGs) into the urethra ex vivo and in vivo. BPGs mimic the 3-D bottlebrush architecture and hydrating properties of natural proteoglycans, and are composed of a synthetic polyacrylic acid (PAA) core (10 kDa or 250 kDa) and natural chondroitin sulfate (CS) bristles (22 kDa). Here, we further characterized BPGs to understand molecular size using dynamic light scattering. Using BPGs, we envisioned modulating physical behavior of the urethra. We hypothesize that through restoration of charge density by introduction of the proteoglycan mimics to the urethral tissue, there will be increased hydration and corresponding improved compliance of the tissue. Here, we examined ex vivo mechanical and physical behavior of porcine urethra in addition to in vivo feasibility of injection of BPGs to the urethra as well as histological and retention assessment. We put forth that the hydrating properties of BPGs have the ability to increase the volume and improve the compliance of urethral tissue, and thus may have the potential to reverse deteriorative tissue changes and restore urethral tissue to a healthier state. Our findings showed that BPGs were well tolerated in vivo, were retained in the tissue for six weeks, the longest time point examined, and modulated mechanical behavior ex vivo. This work has examined feasibility and mechanisms associated with molecular engineering of the urethra using biomimetic proteoglycans.Ph.D., Materials Science and Engineering -- Drexel University, 201
Nanodiamond-based drug delivery system for the modulation of macrophage behavior
No full textChronic inflammation occurs when the body's natural innate immune response is disrupted, resulting in the progression of several diseases, including autoimmune disorders such as rheumatoid arthritis. In rheumatoid arthritis, primary innate immune cells, called macrophages, overproduce inflammatory cytokines and chemokines, leading to the destruction of cartilage and bone tissue, and, consequently, chronic pain. Current treatments for the disease include delivering anti-inflammatory drugs, like dexamethasone (Dex) to macrophages, which have many negative off-target effects, including reduced drug potency and immunosuppression. To limit such side effects, drug-incorporated nano- and microparticles have been investigated as drug delivery carriers to selectively target macrophages via phagocytosis, because of their roles as highly effective phagocytes in the body. Nanodiamond (ND) is uniquely suited to serve as a platform to deliver Dex because of its rich surface chemistry, which allows for adsorption/desorption properties to be easily tuned, as well as their ability to form micron-sized aggregates, which enable optimal phagocytosis. In this thesis, different types of surface-modified nanodiamond (ND) were explored as platforms for the delivery of dexamethasone (Dex) to macrophages both in vitro and in vivo. To first gain a more thorough understanding of the relationship between Dex adsorption and ND surface chemistry, the adsorption properties of other model drugs with different therapeutic applications and chemistries were also explored and compared. The results showed that octadecylamine-functionalized ND (ND-ODA) showed superior adsorption of Dex, compared to carboxylated ND (ND-COOH), likely due to a combination of hydrophobic bonding and electrostatic interactions. Furthermore, these results emphasized that ND surface chemistry can be tailored to promote different types of adsorption properties with drugs of different chemistries. After selecting ND-ODA as the Dex delivery platform, the effects of free Dex, ND-ODA, and Dex-adsorbed ND-ODA (ND-ODA-Dex) on primary human macrophage gene expression and protein secretion was explored. Surprisingly, even in the absence of Dex, ND-ODA had strong anti-inflammatory effects and increased the expression of phagocytic receptors. Interestingly, the adsorption of Dex to ND-ODA further increased some anti-inflammatory effects, but abrogated the effect on phagocytic receptors, compared to its individual components. Because of their proven anti-inflammatory effects in vitro, ND-ODA and ND-ODA-Dex were evaluated for their ability to target and treat macrophages in a murine model of rheumatoid arthritis. Free Dex, ND-ODA, and ND-ODA-Dex were injected locally into the arthritic joints of collagen type II-induced arthritic mice, and physical symptoms of inflammation were clinically scored over time. At the end of the study, the mice were sacrificed, and their arthritic limbs were analyzed for bone and collagen degradation, cell infiltration, and inflammatory protein expression. The ex vivo results correlated with the clinical scoring, which suggested that low doses of ND-ODA and ND-ODA-DEX both elicited anti-inflammatory effects, although the results were variable among animals. These results support the need to conduct a more in-depth investigation. Overall, the ability of ND-ODA to promote anti-inflammatory behavior in macrophages, even in the absence of loaded drugs, suggests its potential for use as an anti-inflammatory therapeutic to directly target macrophages through phagocytosis. Future studies should focus on discovering mechanism through which ND-ODA is anti-inflammatory, as this information holds potential to inform future immunomodulatory nano- and microparticle designs.Ph.D., Materials Science and Engineering -- Drexel University, 201
Evaluating Ductal Carcinoma in Situ Progression via Tissue Oxygenation and Perfusion Using Photoacoustic and Contrast-Enhanced Ultrasound
No full textBreast cancer accounts for 30% of all cancer in women with an estimated 266,000 new cases and over 40,000 deaths in 2018. In the U.S., breast cancer treatments exceed $16.5 billion per year. The gold standard for treatment commonly involves a combination of breast conserving surgery and radiation. Treatments are only successful if the cancers are accurately detected. Breast cancers detection is commonly done through mammography or manual palpation. While mammography has reduced the death rate and allowed for earlier treatments, it is limited by dense breast tissue. Furthermore, about 50% of women experience false-positives. It is reported that approximately 30% of early stage breast cancer, also referred to as ductal carcinoma in situ (DCIS), is over diagnosed and overtreated, causing physical and emotional distress. This thesis aims to address the clinical need for predictive precursors for the aggressiveness and development of DCIS to invasive breast cancer by measuring tissue oxygenation and perfusion using photoacoustic and contrast-enhanced ultrasound imaging. Furthermore, exercise has been proposed as a mechanism to not only reduce the risk of breast cancer, but its progression as well. Therefore, the effects of voluntary physical exercise will be evaluated through the aforementioned parameters above. Mouse models consisting of FVB/NJ mice (n=20) and Tg(C3-1-TAg)cJeg mice (n=10) were evenly divided into exercise and control subgroups, where the exercise groups had access to an exercise wheel. The Tg(C3-1-TAg)cJeg (SV40 Tag) mouseline is genetically predisposed to develop DCIS. Mice were weighed biweekly. Tissue perfusion was measured using the combination of ultrasound contrast agents and high frequency nonlinear imaging. Time intensity curves were generated from perfusion flow within tumor ROIs to extract wash-in rate and area under the curve values. Average SO2 values were compared for tissue oxygenation from photoacoustic images. There was a significant difference between the exercise and control subgroups for the FVB/NJ and SV40 Tag mice. For the FVB/NJ mice, the exercise group exhibited lower weight changes than the control group (0.43 ± 0.70 g vs. 0.99 ± 2.31 g, respectively, p = 0.002). The SV40 Tag mice demonstrated similar differences in weight gain (2.67 ± 1.38 g vs. 3.36 ± 1.36 g, respectively, p = 0.006). There were no differences between the exercise and control subgroups of the FVB/NJ mice with regards to tissue oxygenation (5.16 ± 23.68 % vs. 10.93 ± 27.67 %, respectively, p=0.947). However, for the SV40 Tag mice, the animals with access to voluntary exercise showed mammary tissue more indicative of a hypoxic environment than the control group (-15.64 ± 30.95 % vs. 21.73 ± 27.10 %, respectively, p=0.061). Neither the FVB/NJ or SV40 Tag mice displayed any differences between the exercise or control subgroups when measuring perfusion using contrast-enhanced ultrasound. The WIR was greater for the FVB/NJ (p = 0.685) and SV40 Tag (p = 0.659) exercise groups than the control groups. Likewise, the AUC held a similar relationship between the two subgroups for the FVB/NJ (p = 0.073) and SV40 Tag (p = 0.523) mice. The higher WIR suggest higher vascularization in the exercise groups. Lastly, preliminary results did not support any significant differences between tumor sizes, although the control group did exhibit higher weekly tumor growth (p = 0.902). DCIS-like tumors were visibly seen in all mice at 12 weeks of age, while invasive cancer was indicative of the increasing weekly tumor size at weeks 15. Preliminary results show the potential for tissue oxygenation to be predictive precursor of DCIS progression. By predicting DCIS growth, the proper treatments can be determined to avoid the unnecessary physical, psychological, and financial costs caused by over diagnosis and overtreatments of DCIS.M.S., Biomedical Engineering -- Drexel University, 201
Cell Membrane-Derived Materials
No full textBiological materials are superior to synthetic biomaterials in biocompatibility and active interactions with cells. Recently, cell membrane-derived nanomaterials (CM-NMs) have been actively explored as a novel class of biological materials with various biomedical applications. However, the fundamental properties of CM-NMs were rarely studied. We first designed new methods to quantitatively study the membrane orientation of red blood cell membrane-coated nanoparticles (RBCM NPs) by conjugating ssDNA probes on cell membranes and cell membrane permeability by a nitrobenzoxadiazole-dithionite ion quenching system. We have demonstrated that membranes maintained a correct outside-out orientation on the majority of NPs, and RBCM NPs have a higher permeability to dithionite ions compared with liposomes and live RBCs. Next, we investigated the effect of cell membrane coating on reducing acute inflammatory responses induced by poly(lactic-co-glycolic acid) NPs to scaffold constructs. The release of therapeutics from the NPs is an important strategy to program cells inside the scaffolds for applications in tissue regeneration and immune modulation. We have demonstrated that coating RBC membranes around NPs can eliminate the NP-induced short-term inflammatory responses to scaffolds, including dramatically increased neutrophil infiltration and pro-inflammatory cytokines. We further developed a new class of biological materials: cell membrane-derived hydrogel scaffolds by using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide-activated alginate to crosslink RBCM vesicles. We have demonstrated that RBCM scaffolds can encapsulate hydrophobic molecules and have the potential to release hydrophobic drugs in a sustained manner. RBCM scaffolds show low neutrophil infiltration after subcutaneous injection in mice, and a significantly higher number of infiltrated macrophages than methacrylate alginate (MA-alginate) scaffolds. According to gene expression and surface markers, these macrophages have an M2-like phenotype, which is anti-inflammatory and immune suppressive. There are also higher percentages of macrophages presenting immunosuppressive PD-L1 in RBCM-scaffolds than in MA-alginate scaffolds. Interestingly, the concentrations of an anti-inflammatory cytokine, IL-10 in both types of scaffolds are higher than those in normal organ tissues. This study paves the way to explore scaffolds derived from other cells that present receptors and/or contain cytokines in regulating immune cells or cells critical for tissue regeneration.Ph.D., Materials Science and Engineering -- Drexel University, 201
Auditor Changes by the Firms Just Missing Analysts’ Forecasts
No full textThis study explores a unique setting to examine whether firms tend to change their auditors when their annually reported EPS "just misses" the most recent consensus analysts' forecasts (i.e., within one cent). I find that firms just missing the consensus analysts' forecasts are more likely to switch their auditors than their peer firms. Furthermore, these just-missing firms tend to switch to a more flexible auditor and have lower earnings quality than their peer firms after making the auditor switch, suggesting some opportunism in their switching behavior. In contrast with most opinion shopping literature, this "just-miss" setting allows me to test an implicit form of opportunistic auditor switching behavior -- the shopping of auditors' styles rather than their opinions. The results taken together indicate that firms can successfully shop for a more lenient auditor when the incumbent possibly constrains their ability to meet or beat the earnings target. This also provides empirical evidence in support of DeFond and Zhang (2014)'s argument that opinion shopping may occur in forms other than the reduction of going-concern opinions and still reflect an impairment of auditor independence/quality.Ph.D., Accounting -- Drexel University, 201
Nanopteron-Stegoton Traveling Waves in Mass and Spring Dimer Fermi-Pasta-Ulam-Tsingou Lattices
No full textWe study the existence of traveling waves in mass and spring dimer Fermi-Pasta- Ulam-Tsingou (FPUT) lattices. These are infinite, one-dimensional lattices of particles connected by nonlinear springs, in which either the masses alternate (the mass dimer or diatomic lattice) or the spring forces alternate (the spring dimer). Under the classical "long wave" scaling, the lattice equations of motion turn out to be sin- gularly perturbed. In response to this complication, we apply a method of Beale to produce nanopteron traveling wave solutions with wave speed slightly greater than the lattice's speed of sound. The nanopteron wave profiles are the superposition of an exponentially decaying term (which itself is a small perturbation of a KdV soliton) and a periodic term of very small amplitude. This dissertation builds on the previous work of Faver and Wright on mass dimer lattices to treat spring dimer lattices. Further generalizing the spring forces from the mass dimer case, we allow the springs' nonlinearity to contain higher order terms be- yond the quadratic. This necessitates the use of composition operators to phrase the long wave problem, and these operators require delicate estimates due to the characteristic superposition of different function types from Beale's ansatz. Additionally, the value of the leading order term in the spring dimer traveling wave profiles alternates between particle sites, so that, unlike in the mass dimer, the spring dimer traveling waves are also "stegotons."Ph.D., Mathematics -- Drexel University, 201
When death precedes birth: The embodied experiences of women with a history of miscarriage or stillbirth – A phenomenological study using artistic inquiry
No full textMiscarriage and stillbirth are more prevalent than socially perceived and have often been discussed in nursing and medicine literature as solely a medical event to be managed, not a death to be mourned. Social silence, ambiguity surrounding the nature of what was lost, and a painful experience of having no right to mourn are common experiences faced by women with a history of miscarriage or stillbirth. While more recent psychiatry and counseling research has uncovered the extent of grief, trauma, and psychosocial impact following miscarriage and stillbirth, very few studies have sought to understand the bodily experience of living with this history. The purpose of this phenomenological research study was to understand and describe the embodied experiences of women who have had a miscarriage or stillbirth. With a sample of three participants, the student researcher carried out individual expressive movement activities exploring the stages surrounding the pregnancy loss, followed by semi-structured verbal interviews focusing on their movement experience. The student researcher integrated artistic inquiry methods throughout the analysis of the interviews to enhance the understanding of each woman's current, lived-body experience. Five universal themes emerged from the interview analysis: Momentum of new life; Stuck in emptiness; Where is my body and where am I?; We go together; and Love does not forget. The author suggests that the results from this study may be used to inform the integration and practice of dance/movement therapy interventions in miscarriage and stillbirth bereavement counseling and future dance/movement therapy research studies.M.A., Dance/Movement Therapy and Counseling -- Drexel University, 201
Investigating Supplemental Context for Word Sense Disambiguation
No full textThe key to word sense disambiguation is context. Because most words have multiple meanings (i.e. senses), there arises ambiguity when interpreting a word in isolation. Additional information is required to resolve the ambiguity. This additional information is referred to as context. Microtext (e.g., tweets) present a special case where messages are limited to a small number of characters, thereby severely limiting the available context in the text itself. This work is motivated by the importance of Twitter as a unique data source, and the difficulties of precise data collection when confronted with the daunting volume of messages that flow through the system on regular basis. Twitter has become a valuable source of information for academic researchers, industry analysts, marketing organizations, and others. The ultimate goal is to develop a tool that can help users collect relevant Twitter data from the vast sea of messages in the Twitter search index, or from streaming data sources, by leveraging additional context opportunities to aid in word sense disambiguation of a search term. While the language used in tweets presents problems, the Twitter platform offers opportunities to help make sense of users' messages. Various data retrieval mechanisms made available through a variety of APIs (application programing interfaces) allow developers to request additional information that may be used to form a supplemented context within which to better understand a message. In particular, this combination of message text and supplemental context may be employed to disambiguate among the meanings (i.e. senses) of a search word. We investigate two sources of supplemental context; previous tweets from a message's author (i.e. a twitter timeline) and tweets within a temporal window relative to the tweet under investigation's creation timestamp. Contexts for the former were collected on-demand from a RESTful Twitter API while context for the later was collected in bulk using a streaming API resulting in an experimental pool of over 10 million tweets. We propose a simple heuristic that can aid in the automated collection of supplemental context. The results of the heuristic's application are explored using a standard approach to word sense disambiguation combined with a variety of underlying concept-to-concept similarity measures. In addition, we develop a Blue Standard approach to generating sense-tagged test data. This work is motived by issues and limitations associated with employing human coders. The performance of systems that process human (natural) language has always been evaluated against a "gold standard" that is human derived. Engaging people to create tagged corpora for use as gold standards in natural language processing research is a time consuming and expensive proposition. Reuse of existing data is often the only viable option, even if the domain of discourse, writing style (e.g., formal vs. informal) or other significant attributes of the text or coding are not well suited to answering a particular research question. We propose a semi-supervised instance tagging methodology designed to produce sense tagged twitter data for the purpose of studying word sense disambiguation in social media. The proposed approach leverages the foundational work by Yarowsky (1993) who demonstrated that collocations are strongly indicative of word sense. We use the Blue Standard approach to build a test set of over 380,000 sense tagged tweets for use in our WSD experiments.Ph.D., Information Studies -- Drexel University, 201
PSD-95 alters GABAergic inhibition in the prefrontal cortex
No full textPostsynaptic Density Protein-95 (PSD-95) is a major scaffolding protein in the excitatory postsynaptic density and regulator of synaptic maturation by interacting and recruiting N-methyl-D-aspartic acid (NMDA) and [alpha]- amino-3-hydroxy-5-methyl-4-isox-azolpropionic acid (AMPA) receptors. PSD-95 deficiency has been linked to cognitive and learning deficits implicated in neurodevelopmental disorders such as autism and schizophrenia. In previous studies shown within the hippocampus, PSD-95 deficiency causes a significant reduction in the excitatory response at the postsynaptic membrane. However, little is known whether PSD-95 deficiency will affect gamma-aminobutyric acid (GABA)ergic inhibitory synapses in the medial prefrontal cortex (mPFC). Using a PSD-95 transgenic mouse model (PSD-95 +/-), we study how PSD-95 deficiency affects GABAA receptor expression and function in the mPFC of adolescent mice. Using Western blot, we show a significant decrease in protein expression levels of PSD-95 in the PSD-95 +/- mouse, confirming sufficient reduction of the protein. Our results also show a significant increase in the GABAA receptor subunit [alpha]1 and a trending increase in the subunits [alpha]2. We utilized whole-cell patch clamp to record spontaneous inhibitory postsynaptic currents (sIPSCs) as a measure of GABA-mediated current in layer 5 pyramidal neurons of the mPFC. We found significant increases in sIPSC frequency and amplitude in PSD-95+/- mice. In addition, we show a decrease of evoked excitatory postsynaptic currents (eEPSCs) and a significant increase in evoked IPSCs (eIPSCs), leading to a significant decrease in the excitatory-to-inhibitory balance in PSD-95+/- mice. Our study suggests that PSD-95 deficiency causes an increase in the inhibitory response in the mPFC due to an increase in GABA receptor presence and function, consequently leading to a shift in the excitatory/inhibitory balance. This study will provide novel insights into the importance of GABAergic transmission in the mPFC in response to PSD-95 deficiency and its potential link with cognitive and learning deficits associated with autism and schizophrenia.M.S., Biomedical Studies -- Drexel University, 201