http://hdl.handle.net/1721.1/7893 2013-06-19T15:03:33Z http://hdl.handle.net/1721.1/78244 Synthesis of composite hydrogels incorporating D,L-cyclic peptide nanotubes as a platform for materials engineering Tay, Pei Kun Richie Composite hydrogels find increasing use as biomaterials because the addition of a filler often improves on the material properties of the original matrix, or provides new optical, magnetic, conductive or bioactive functionalities not inherent to the hydrogel. In this work we synthesized nanocomposite gelatin methacrylate (GelMA) hydrogels that incorporate D,L-cyclic peptide nanotubes. These nanotubes are biocompatible, stiff and their physical and chemical properties can be tailored simply by changing the amino acid sequence of the peptide. We show that the nanotubes successfully integrated into the hydrogel matrix and provided some mechanical reinforcement, without affecting hydrogel porosity or hydration characteristics. We will be using this composite system as a platform for engineering hydrogels with unique physical and biological properties to the hydrogel, for application as biological scaffolds. Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2012.; Cataloged from PDF version of thesis.; Includes bibliographical references (p. 27-30). 2012-01-01T00:00:00Z http://hdl.handle.net/1721.1/78159 Disease marketing and patient coping : a research study Lau, Hew Mun BACKGROUND: There is a high prevalence of disease marketing actions in the United States that are targeted towards patients with chronic illness. However, no study has assessed the direct effects of these marketing actions on patient coping attitudes and behaviors. OBJECTIVES: This study aims to investigate whether the mere presence of disease marketing impacts patient coping and if so, how do they affect patients' coping attitudes and behaviors. METHODS: We conducted a controlled experiment using online questionnaires to assess the disease perceptions, coping decisions and disease disclosure behaviors of 108 subjects. The subjects were divided into two groups where the experimental group (N = 55) was shown marketing actions associated with a fictitious disease called Karlsen's Disease while the control group (N = 53) was not shown any marketing actions. The subjects were then asked a series of questions related to health-related coping behaviors and non-health related social behaviors. T-tests and chi-square analyses were used to analyze the behavioral differences between the experimental (high-marketing) and control (no-marketing) groups. RESULTS: Subjects in the high-marketing group were overall significantly more willing to draft a will than subjects in the no-marketing group (t(106) = 2.64, p = 0.01); High-marketing group subjects were overall significantly more likely to wear a medical ID bracelet than no-marketing group subjects (c²(1, N = 108) = 3.71, p = 0.05); Among subjects who were willing to request a menu accommodation at a dinner party, those who were in the high-marketing group were significantly more likely to disclose their disease to the party host (c²(1, N = 90) = 4.65, p = 0.03); Subjects in the high-marketing group were also significantly more likely to anticipate greater understanding from the party host towards their menu accommodation request. When controlled for gender, women in the high-marketing group were more likely to join a patient support group (t(61) = 1.75, p = 0.09), and less likely to ask family and friends to shave their heads in show of solidarity (t(18) = -1.97, p = 0.07) than women in the no-marketing group; Men in the high-marketing group were more likely than men in the no-marketing group to disclose their health condition to the dinner party host (c²(1, N = 47) = 3.61, p = 0.06). Finally, among subjects with at least a 4-year college degree, those in the high-marketing group were more willing than those in the no-marketing group to wear a face mask to protect themselves from airborne pathogens in crowded public places (t(61) = 1.79, p = 0.08). CONCLUSIONS: Based on our results, the presence of disease marketing is anticipated to have a general positive impact on patient coping attitudes and behaviors. Chronically ill patients exposed to disease marketing actions are expected to anticipate less stigma from others, have increased willingness to disclose their illness and adopt health seeking behaviors. Disease marketing is also expected to have differential impact on patients based on their gender and level of education. Follow-up studies using real patients with chronic illness should be carried out to confirm the findings from this study. Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2012.; Cataloged from PDF version of thesis.; Includes bibliographical references (p. 80-87). 2012-01-01T00:00:00Z http://hdl.handle.net/1721.1/78158 From bench to bedside : impact of conflict-of-interest restrictions at academic medical centers on clinical trials Campbell, Elyssa Sarah Successful translation of scientific discovery into new medicines is most successful with collaboration between academics - scientists and physicians - and industry. In recent years, there has been increasing concern at academic medical centers about the impact of relationships with industry on patient care and student education. This has generally resulted in more stringent conflict-of-interest rules. This paper seeks to better understand the impact of these conflict-of-interest rules. In the first part, it explores research to-date on the importance of relationships between industry and academia and discusses some of the concerns that have arisen. In the second part, this relationship is better characterized with clinical trial data. The findings suggest that there is a strong trend towards schools with higher conflict-of-interest rules having fewer clinical trials. This suggests that although there may be benefits to stricter regulation, there are trade-offs in terms of clinical translation. Thesis (S.M. in Health Sciences and Technology)--Harvard-MIT Division of Health Sciences and Technology, 2012.; "September 2012." Cataloged from PDF version of thesis.; Includes bibliographical references (p. 37-40). 2012-01-01T00:00:00Z http://hdl.handle.net/1721.1/78156 Opportunities and challenges in oncology targeted drug development : an assessment of the use of prevalence and companion diagnostic performance thresholds to guide clinical trial strategies Vital, Heather Stacey Tomkinson Targeted, especially stratified or biomarker-guided, therapies offer significant advantages over traditional oncology therapies in certain settings. Selecting patients most likely to respond to a drug increases the therapeutic efficacy while reducing toxicities and may accelerate regulatory approval since smaller clinical trials are needed to demonstrate benefit. Several drugs, including vemurafenib and crizotinib have demonstrated these benefits along with commercial success. However, significant risk exists for the drug developer since approval may be threatened if they fail to meet unclear and differing yet parallel requirements for both the drug and the required companion diagnostic. Tumor biology is also increasingly complex since recent studies suggest that there are limited numbers of individual driver mutations, complicated interactions throughout signaling pathways as well as extensive tumor heterogeneity, all of which will challenge the effectiveness of targeted therapies. Clinical trial strategy decisions can greatly impact the success of a targeted therapy due to these challenges. While therapeutic efficacy is considered important, biomarker prevalence and companion diagnostic performance have been shown to be as important, yet more informative at the time decisions are made. I hypothesized that common prevalence and companion diagnostic performance thresholds are being used to guide biomarker-guided clinical trial strategy decisions for targeted oncology therapies. Seventeen interviews with preclinical, clinical or translational leads were conducted across a focused set of ten "pathway-modifying" cancer drug programs (CDK4/6, MDM2 and P13KP inhibitors) that reflect the biological complexity of future targeted therapies. These interviews provided empirical data as to how biomarkers are being incorporated into current clinical trial decisions. All respondents were planning to use a companion diagnostic for their program, however, the use of biomarkers varied significantly. For those programs with ongoing clinical trials in phase I and II, 54% (n=7/13) were pursuing a biomarker-guided strategy while 46% (n=6/13) were using an initial all-comers strategy. This fairly equal split separated when compared by phase where trials in phase I and 1/11, 60% (n=6/10) were using an all-comers strategy but for those trials in phase II (n=3), all were using biomarker-guided strategies. A key finding of the interviews was that 66.7% (n=4/6) were planning biomarker enrichment as part of expansion plans. Disproving my hypothesis, however, common thresholds for neither biomarker prevalence nor companion diagnostic performance were being used to guide these decisions. Biomarker prevalences of 50-100% were stated as potentially appropriate for an all-comers strategy. Companion diagnostic performance thresholds were even less influential as only a few respondents provided a general range of desired sensitivity and specificity. This study found that actions of drug developers are not necessarily following the emerging recommendations for targeted therapies due to the significant challenges of biomarker and companion diagnostic development. Thesis (S.M. in Health Sciences and Technology)--Harvard-MIT Division of Health Sciences and Technology, 2012.; Cataloged from PDF version of thesis.; Includes bibliographical references (p. 67-70). 2012-01-01T00:00:00Z