One for All: Employing People with Disabilities

One for All: Employing People with Disabilities Krista Simeone Faculty Sponsor: Susan Roush, Physical Therapy The creators of our constitution believed that all men are endowed with certain unalienable rights, one of which being the Pursuit of Happiness. We all measure happiness in our own lives differently, and many of us find happiness in what we do each day. President Theodore Roosevelt once said “Far and away the best prize that life offers is the chance to work hard at work worth doing.” Everyone should have the privilege of serving a purpose within their society, however, people with disabilities often find themselves overlooked and under-represented within the workforce due to misconceptions, stereotypes, and stigmas we have attached to what it means to be “disabled.” After graduation, I plan to become involved in public policy relating to disability issues by moving to Washington, DC and enrolling in a vocational rehabilitation counseling graduate program. In order to accomplish these goals, I need to have a deep understanding of what the employment situation looks like for people with disabilities, the programs in place to facilitate employment, and what still needs to be addressed. In light of this, my Senior Honors Project was an in-depth look at what disabled Americans face when attempting to enter the workforce, and what is being done to help them. Furthermore, I explored disability employment policy in two non-U.S. countries: China and the United Kingdom. While these countries are different from the United States (and in China’s case, vastly different), they offer something unique in the realm of employment efforts for people with disabilities. Furthermore, my presentation includes several interviews with disabled individuals from all walks of life describing their personal employment experiences, a summary of the events that took place at an informational disability employment workshop I coordinated at the University of Rhode Island on April 14, 2011, and my own public policy proposal regarding disability awareness targeting American employers. America works better when everyone is working, and my project invites the URI community to learn more about what is being done to ensure that people with disabilities are given every opportunity to gain employment and succeed as a worker. Keywords: disabled, employment, policy, America, UK, Chin

Proteomic test for anti-PD-1 checkpoint blockade treatment of metastatic melanoma with and without BRAF mutations

Abstract The therapeutic landscape in metastatic melanoma has changed dramatically in the last decade, with the success of immune checkpoint inhibitors resulting in durable responses for a large number of patients. For patients with BRAF mutations, combinations of BRAF and MEK inhibitors demonstrated response rates and benefit comparable to those from immune checkpoint inhibitors, providing the rationale for sequential treatment with targeted and immunotherapies and raising the question of optimal treatment sequencing. Biomarkers for the selection of anti-PD-1 therapy in BRAF wild type (BRAF WT) and in BRAF mutated (BRAF MUT) patients help development of alternative treatments for patients unlikely to benefit, and might lead to better understanding of the interaction of checkpoint inhibition and targeted therapy. In this paper we evaluate the performance of a previously developed serum proteomic test, BDX008, in metastatic melanoma patients treated with anti-PD-1 agents and investigate the role of BRAF mutation status. BDX008, a pre-treatment proteomic test associated with acute phase reactants, wound healing and complement activation, stratifies patients into two groups, BDX008+ and BDX008-, with better and worse outcomes on immunotherapy. Serum samples were available from 71 patients treated with anti-PD1 inhibitors; 25 patients had BRAF mutations, 39 were wild type. Overall, BDX008+ patients had significantly better overall survival (OS) (HR = 0.50, P = 0.016) and a trend for better progression-free survival (PFS) (HR = 0.61, P = 0.060) than BDX008- patients. BDX008 classification was statistically significant in the analyses adjusted for mutation status, LDH, and line of treatment (P = 0.009 for OS and 0.031 for PFS). BRAF WT BDX008+ patients had markedly long median OS of 32.5 months and 53% landmark 2 years survival, with statistically significantly superior OS as compared to BDX008- patients (HR = 0.41, P = 0.032). The difference between BDX008+ and BDX008- in PFS in BRAF WT patients and in OS and PFS in BRAF MUT patients did not reach statistical significance, though numerically was consistent with overall results. The test demonstrated significant interaction with neutrophil-to-lymphocyte ratio (NLR) (PFS P = 0.041, OS P = 0.004). BDX008 as a biomarker selecting for benefit from immune checkpoint blockade, especially in patients with wild type BRAF and in subgroups with low NLR, warrants further evaluation