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Mandatory reporting of sexual violence by faculty and staff at Hometown University: an evaluation study
No full text2019-03-05Sexual violence is a significant problem on college and university campuses in the United States affecting large percentages of students during their studies and later in life. To confront this alarming issue, the United States Department of Education’s Office of Civil Rights issued new guidance under Title IX of the Civil Rights Act of 1964 to colleges and universities beginning with the “Dear Colleague Letter” in April of 2011. The guidance was broad and included a requirement for institutions to identify faculty, staff, and students to serve as Mandatory Reporters based on the types of relationships which they have with students. The purpose of this study was to determine the degree to which Hometown University is meeting its organizational goal of creating a safe learning environment for students. Knowledge, motivation, and organizational influences affecting Mandatory Reporters were identified using the Clark and Estes (2008) gap analysis model. Interviews and document analysis of participant reflections revealed four themes elucidating two knowledge influences, two motivation influences, and two organizational influences. Additionally, this study recommended a comprehensive learning and training program for Mandatory Reporters to address the identified knowledge, motivation, and organizational gaps. The recommended training program implementation and evaluation is guided by the Kirkpatrick and Kirkpatrick (2016) New World Model for Evaluation, and the four levels of implementation and evaluation tools are detailed. Finally, recommendations for further research are presented
Advanced applications of high frequency single beam acoustic tweezers in fluid and cell mechanics
No full text2019-02-20Single beam acoustic (SBA) tweezers represent a new technology for particle and cell trapping. The advantages of SBA tweezers are their deep penetration into tissues, reduction of tissue damage, and ease of application to in vivo study. The use of these tools for applications in drug delivery in vivo has to meet the following conditions: large penetration depth, strong trapping force and tissue safety. The reasonable penetration depth of SBA tweezers for developing in vivo applications was discovered by a previous study conducted in water with zero velocity. However, capturing objects in a flowing fluid can provide more meaningful results. In the dissertation, we investigated the capability of SBA tweezers to trap red blood cells (RBCs) and polystyrene microparticles in flowing RBC suspensions. ❧ On the other hand, cellular biomechanics represent a significant characteristic in metastasis. It has already been known that highly invasive cancer cells are typically more compliant than weakly invasive cancer cells, allowing them to migrate easily. The presence of chemotherapy-resistant cells can be detected in the bone marrow (BM) and peripheral blood (PB) and is called minimal residual disease (MRD). Once MRD is diagnosed, patients are associated with a higher risk of relapse in acute lymphoblastic leukemia (ALL). Studying cell mechanics for ALL in drug resistance is crucial. However, the research of the mechanical properties in drug resisted ALL cells has not been widely discovered. Single beam acoustic (SBA) tweezers are a novel and promising technology to quantify the mechanical phenotype of cells. Here, a non-contact acoustic trapping method based on the SBA tweezer for quantification of deformability of numbers of types ALL cells and those survived ALL cells (drug resisted ALL) treated by chemotherapy drugs was demonstrated. The research showed that those survived cells after 7-day chemotherapy drug treatment revealed more compliant than ALL cells in media control by using the SBA tweezer. Two antibodies and oleic acid were also added to cells to investigate the mechanical property, and reveled a larger compliance comparing with control group. The study demonstrated that SBA tweezers is a promising label free tool for non-contact quantitative discrimination of mechanical phenotypes of cells. ❧ Young’s modulus plays an important role in cell mechanics due to a fundamental feature in regulating a diverse array of physiological processes. Traditional methods, AFM, micropipette, optical tweezers and microfluidic channels, have their own disadvantages. A new concept, called Young’s modulus map, was proposed to estimate leukemia cells by SBA tweezers associated with microparticles with different agarose concentrations. In addition, finite element analysis (FEA) in FEBio software was used to simulate the deformation of cells. ❧ The motility of ALL in the media control and drug resisted ALL cells was studied. The experimental results revealed that the drug resisted ALL cells after the treatment decreased the velocity and migration distance than cells in media control. These results elaborated that the stiffness of drug resisted ALL cells expressed the inverse relationship with the motility and migration pattern of leukemia cells proved by using deep-tissue imaging
An overview of the dental and skeletal relationships in individuals of Vietnamese ancestry
No full text2019-03-11Background: Orthodontic treatment norms that have traditionally been used have been based off of the dental and skeletal relationships found in Caucasians. Studies have since been conducted on a variety of ethnic groups in order to provide reference standards specific to different populations. Limited literature exists, however, on the Vietnamese population, which reduces the ability to appropriately diagnose and treat individuals of such descent accordingly. ❧ Objective: The purpose of this study was to explore and establish a general overview of the dental and skeletal topography in patients of Vietnamese descent. ❧ Materials and Methods: Initial records, which included study models and lateral cephalograms, were collected in a private orthodontic practice in Canoga Park, California and de-identified by the private practitioner prior to use in this study. Inclusion criteria were as follows: immigrant or first generation Vietnamese-American, complete diagnostic records, no previous orthodontic treatment, permanent first molars erupted into occlusion, absence of pathology, no edentulous spaces as a result of caries or congenital reasons, and a medical history void of syndromes or craniofacial abnormalities. Of 124 initial records collected, 119 were used for this study. Study models were evaluated by a single investigator for the Angle classification (right and left molars), overjet, overbite, presence of shovel-shaped incisors, crossbite tendency, and arch form. Lateral cephalograms were digitally traced by the private practitioner using Steiner and Wits analyses. Descriptive statistics were then completed on the collected data and compared to corresponding data previously published on other ethnicities. ❧ Results: A Class I, II, and III molar relationship was observed in both the total sample and each gender in order of decreasing frequency. The mean overjet of the sample was 3.5 ± 2.8 mm and the mean overbite of the sample was 2.7 ± 1.8 mm. Maxillary incisors in 39.5% of the sample exhibited the tooth shoveling quality. Crossbite relationships of any kind were present in 47.9% of the patients, while an edge-to-edge anterior relationship was present in 3.4%. Ovoid arch forms were the most common in the sample, being observed in 68.0% of the maxillas and 60.5% of the mandibles of the patients. The mean ANB of the sample was 3.1 ± 2.5°while the mean SN-GoGn was 37.3 ± 5.5°. Wits appraisal was calculated with a mean value of -0.67 ± 3.14 mm for the males and -0.92 ± 3.76 mm for the females in the study. ❧ Conclusion: Vietnamese individuals of the sample displayed Class I, II, and III molar relationships in decreasing order of prevalence. Additional dental features observed in the sample included elevated overjet and overbite values compared to ideal standards, increased crossbite distribution, and a common tendency for ovoid arch forms. Tooth shoveling was present and expected in the sample, but the prevalence was not as high as anticipated based on previous reports. On average, Vietnamese individuals presented with an elevated ANB and steeper mandibular plane angle compared to Caucasians, and a more negative Wits value for the females than the males
Development of new bifunctional iridium complexes for hydrogenation and dehydrogenation reactions
No full text2019-03-08Hydrogenation and dehydrogenation are among the most important reactions in catalysis. As demonstrated in Chapter 1, homogeneous catalysts based on bidentate iridium complexes have a special place in the field of hydride transfer reactions, therefore, were the subject of my investigation. ❧ Chapter 2 describes Cp ⃰ IrCl(2-pyridylmethyl)toluenesulfonamide bidentate complex that effects transfer hydrogenation through a metal-ligand cooperative mechanism through reversibly dearomatized ligand. This complex accesses a mechanism for transfer hydrogenation of ketones with isopropyl alcohol that has not been previously reported. It is the first example of metal-ligand cooperation via reversible ligand dearomatization outside of the pincer scaffold. ❧ Besides the transfer hydrogenation, a newly synthesized family of iridium sulfonamide complexes, including the one mentioned above, act as hydrogenation and water oxidation catalysts. This is demonstrated in Chapter 3. ❧ Chapter 4 describes the base-pendant ligand-metal bifunctional catalytic scaffold wherein the concept of a photobase, compound that becomes more basic in the excited state (pKₐ < pKₐ ⃰ ), is used to switch the proton acceptor ability on an active site of the catalyst. In this system quinoline is an efficient photobase that preserves its unique properties in the close proximity of an iridium center and the photochemistry of the metal is orthogonal to the photobase system. As a result, deprotonation of an aliphatic alcohol by the new iridium complex became possible. This is the first case of metal-orthogonal optical pKₐ control in a transition metal complex. ❧ The same quinoline-containing complex acts as a catalyst for light-driven formic acid dehydrogenation, as revealed in Chapter 5. However, it was demonstrated that the presence of the quinoline moiety does not affect the reaction. Nevertheless, this catalytic scaffold can operate in neat formic acid, at ambient temperature, and more importantly without added base. ❧ Chapter 6 describes a high-utility technique for the conversion of crude glycerol to value-added lactides based on the oxidative conversion of glycerol to lactate. The process utilizes a structurally novel iridium catalyst and enables unprecedented efficiency, longevity, and conversion in the oxidation of glycerol to lactic acid. This enables a very practical alternative to fermentation, which is the only technology known to be applied on a large scale. ❧ Chapter 7 recounts the preliminary data on the synthesis of new gadolinium complexes for the site-specific labeling of proteins that can also be utilized as an MRI contrast agent
High intensity interval training for breast cancer patients receiving anthracycline-based chemotherapy
No full text2019-03-11Breast cancer patients were at greater risk for cardiovascular disease (CVD) mortality, compared to age-matched women without breast cancer. CVD mortality was two times higher among breast cancer patients who receive chemotherapy. Specifically, anthracycline-based chemotherapy was of particular concern due to the impairment of vascular endothelial function and vascular wall thickness, as well as dysregulation of extracellular matrix (ECM) in vasculature induced by increased oxidative stress caused by anthracycline-based chemotherapy. One strategy to offset these impairments was a form of exercise referred to as high-intensity interval training (HIIT) which improved vascular endothelial function by decreasing the level of oxidative stress, the main cause of the anthracycline-induced vascular complication. The purpose of this study was to assess the feasibility of implementing and conducting an 8-week HIIT in breast cancer patients undergoing anthracycline-based chemotherapy. Further, we determined the effects of an 8-week HIIT on vascular endothelial function, vascular wall thickness and the ECM-regulating enzymes in breast cancer patients undergoing anthracycline-based chemotherapy. We designed a pilot study to include 30 breast cancer patients undergoing anthracycline-based chemotherapy. Following informed consent and baseline measures, participants were randomized to either the HIIT group or the delayed (DEL) group. ❧ Chapter 3 was design to determine the feasibility of HIIT in breast cancer patients undergoing anthracycline-based chemotherapy. Thirty women initiating anthracycline-based chemotherapy were randomized to either the HIIT or delayed (DEL) groups. The HIIT group participated in an 8-week HIIT intervention occurring 3 times weekly. Adherence measures used to define feasibility were calculated for each participant by computing (1) the average weekly minutes of HIIT over 8 weeks and (2) the number of sessions attended and multiplied by 100 (percentage of sessions). The HIIT intervention was considered feasible if more than 50% of participants completed both an average of 70% of weekly minutes (63/90 minutes) and attended 70% exercise sessions (17/24 sessions). Feasibility was demonstrated by: 12 of 15 participants met both feasibility criteria average weekly minutes of exercise completed was 78±5.1 out of 90 min and 19.2±2.1 out of 24 sessions (82.3%). ❧ Chapter 4 was conducted to demonstrate the effects of HIIT on vascular endothelial function and vascular wall thickness in breast cancer patients undergoing anthracycline-based chemotherapy. The HIIT group participated in an 8-week HIIT intervention occurring 3 times per week on a cycle ergometer. The DEL group was offered the HIIT intervention after 8 weeks. Outcomes were measured at week 0 and week 9. baFMD was measured from the brachial artery diameter at baseline (D0) and 1min after cuff deflation (D1); percent change was calculated by measuring brachial artery diameter 1min after cuff deflation relative to the baseline [baFMD=(D1−D0)/D0×100]. The cIMT was obtained from the posterior wall of common carotid artery 10mm below the carotid bulb. The region of interest was identified at the intima and media on the far wall of the vessel. Vascular endothelial function was assessed using brachial artery flow-mediated dilation (baFMD) and vascular wall thickness was measured using carotid intima media thickness (cIMT). Post-exercise, baFMD significantly increased [4.3; 95% confidence interval (CI): (1.5, 7.0), P=0.005] in HIIT versus delayed (DEL) group. cIMT did not significantly change [0.003, 95% CI: (-0.004, 0.009), P=0.40] in the HIIT group, while IMT significantly increased from baseline to post-intervention (0.009, 95% CI: 0.004, 0.010, P=0.003) in DEL group. ❧ Chapter 5 was focused on the effects of HIIT on ECM-regulating enzymes in breast cancer patients undergoing anthracycline-based chemotherapy. The HIIT group participated in an 8-week HIIT intervention occurring 3 times per week on a cycle ergometer. The DEL group was offered the HIIT intervention after 8 weeks. Outcomes were measured at week 0 and week 9. MMP-2 and -9 were tested as a single batch at study completion and processed using the magplex suspension bead array immuno-assays on a Luminex 100 Bioanalyzer (Luminex 100, Luminex Corporation, Austin, Texas) according to the kit manufacturer’s instructions (Milliplex ELISA kits, Millipore, MA). ECM regulating enzymes were measured analyzing the level of matrix metalloproteinases (MMPs) in serum sample. There was a significant within-group decrease in MMP-9 in the HIIT group (-37.4%; P=0.01) while MMP-9 in the DEL group was not significantly changed (-21.7%; P=0.10) following 8 weeks. ❧ Overall, this dissertation demonstrated that HIIT is a feasible exercise strategy for breast cancer patients undergoing anthracycline-based chemotherapy. HIIT significantly improved baFMD along with maintenance of cIMT, and reduced MMP-9 while MMP-9 was not altered in the DEL group. Unexpectedly MMP-2 was significantly increased in both HIIT and DEL groups. This study may impact cancer survivorship and future cardiovascular health by demonstrating that HIIT is a lifestyle strategy that may improve vascular endothelial function in breast cancer patients during chemotherapy, thereby reducing the risk of future CVD
Promising practices to promote and sustain a college-going culture: a charter-school case study
No full text2019-04-26The main function of a school is to prepare students to become contributing members of society. Individuals with a college degree have greater job opportunities, earn higher incomes, actively participate in civic engagement, and have a better quality of life. Education plays a particularly critical role in ending cycles of poverty and creating a pathway to economic self-sustainability for low-income and under-represented students. Yet, an achievement gap exists in college enrollment and graduation for the students who need it most. Research clearly shows the need for high schools to establish college-going cultures that encourage students to pursue post-secondary education. These cultures promote college talk, build student social capital, provide counseling, challenge students with rigorous work, and engage parents in the education process. Like other school reform initiatives, establishing a college-going culture requires principal leadership. School is one of many systems that influence the achievement of low-income and under-represented students. Brofenbrenner’s Ecological System Theory provided an ideal model for studying the interdependent systems that promote college-going cultures. The study used a qualitative case-study design to examine the strategies of school leaders to promote and sustain college-going culture at a California charter high school. The research explored barriers and promising practices to promote and sustain a college-going culture for low-income and under-represented students. Most important, this study provided a roadmap for low-income and under-represented students to learn and thrive in a college-going culture, providing access for these students to permanently end the generational cycles of poverty for themselves and their children
Enhancing chimeric antigen receptor-engineered immune cell therapy with synthetic biology and nanomedicine
No full text2019-04-26Chimeric antigen receptor (CAR)-engineered adoptive cell therapy has garnered much attention as it has been used in conjunction with or as a replacement for traditional cancer treatments. However, its uses, particularly in solid tumors, have been tempered by serious adverse side effects and lackluster clinical results. The following chapters will focus on improving CAR-based therapy with antibody mimetic proteins in place of scFvs (Chapter 1), CAR-NK cells conjugated to chemotherapy-loaded liposomes (Chapter 2), and CAR-NK cells with additional cytokine and suicide switch transgenes (Chapter 3). Synthetic biology and nanomedicine are two areas of biomedical research which can synergize with CAR-related treatments to create safer, more effective cancer therapies
The role of ATAD3A in the progression of non-alcoholic fatty liver disease (NAFLD)
No full text2019-04-26To understand the functions of ATPase family AAA domain containing 3A (ATAD3A), a mitochondrial inner membrane protein, in the progression of NAFLD, we generated a ATAD3A knockout (KO) cell line by clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology using human liver cancer cell line Huh7. MBCD/CH (Methyl-B-cyclodextrin with cholesterol loading) and a combination of MBCD/CH and 58035 (an inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT) ) were used to accumulate cholesterol and free cholesterol (FC) in cells, respectively. We found that after KO of ATAD3A, the PKR-like ER-resistant kinase (PERK) and activating transcription factor 6 (ATF6) signaling pathway of endoplasmic reticulum (ER) stress was downregulated, while the inositol-requiring enzyme-1a (IRE1a) signaling pathway was activated after FC accumulation, suggesting the role of ATAD3A played diverse functions in regulating ER stress. In addition, loss of ATAD3A tended to reduce lipid peroxidation and downregulate antioxidant levels under FC accumulation. Apoptosis, autophagy and lysosome formation, which is dependent on FC accumulation, were exacerbated after loss of ATAD3A. Taken together, we show that ATAD3A plays diverse roles in the progression of NAFLD which can shed light on the further studies of ATAD3A in liver
Quality literacy instruction in juvenile court schools: an evaluation study
No full text2019-04-26This study employed a qualitative approach to evaluate quality literacy instruction in a juvenile court school. Teachers’ ability to develop and implement six literacy-based units of study were examined. Teachers from a juvenile court school in central California participated in interviews and an observation of their classroom regarding their literacy instructional practices. Interview responses, observation field-notes and literature were analyzed to triangulate teacher practices and perspectives regarding the development and implementation of literacy-based units of study. A modified Clark and Estes (2008) Gap Analysis Framework was utilized to assess knowledge, motivational, and organizational influences on teachers’ ability to develop and implement six literacy-based units of study. The findings of this inquiry revealed that teachers possessed the motivation to develop six literacy-based units of study but faced knowledge and organizational barriers hindering attainment of their stakeholder goal. Responses indicated that teachers possess self-efficacy and attributed the success or failure to develop and implement literacy-based units of study to their own efforts. Partially validated and validated gaps in teacher knowledge and organizational influences hindered teachers from developing and implementing literacy-based units of study. The findings of this study emphasized the need for professional learning opportunities to meet the need of juvenile court school students, clear communication of the organizational goals and vision, and effective feedback on instructional practices. The development and implementation of an effective plan to address these knowledge and organizational issues could assist juvenile court schools in improving literacy instruction for incarcerated students
Statistical analysis of a Phase II study of AMG 386 versus AMG 386 combined with anti-VEGF therapy in patients with advanced renal cell carcinoma
No full text2019-04-28The VEGF pathway is associated with angiogenesis and is an important target for molecular therapies for treating Renal Cell Carcinoma. Existing anti-VEGF therapies, including Bevacizumab, Pazopanib, Sorafenib, and Sunitinib, are available to treat this cancer. However, the presence of alternative pathways, such as the angiopoietin-Tie pathway, is hypothesized to lead to anti-VEGF therapy resistance. AMG 386 was developed to treat renal cell carcinoma through the angiopoietin-Tie pathway. In a Phase II randomized clinical trial, the overall response rate of AMG 386 alone and in combination with an anti-VEGF therapy was assessed. We analyzed the data from this trial to evaluate the efficacy of AMG 386. For this Phase II randomized trial, AMG 386 alone and in combination with anti-VEGF therapy were evaluated separately. The primary endpoint was overall response. For this thesis, we compared the two arms, although this was not done for the original trial. ❧ A total of 35 evaluable patients were available in this study, where we evaluated baseline characteristics, toxicity, response, and progression-free survival. Toxicity was summarized by grade and toxicity system; also, using logistic regression, odds ratios were calculated to analyze the association between hematologic and non-hematologic toxicities and baseline explanatory variables. Response was summarized in terms of RECIST Criteria and a waterfall plot. Fisher’s Exact test and Wilcoxon Rank Sum were used to test the difference between baseline explanatory variables in the two treatments. A Kaplan Meier plot and log-rank test were used to analyze progression-free survival. ❧ The primary conclusion is that neither AMG 386 alone or in combination with an anti-VEGF therapy was effective in treating advanced renal cell carcinoma. Only two patients—both in the combination arm—experienced an objective response to treatment, and 37% of the patients in both arms had stable disease as their best response