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Social entrepreneurship is a growing trend for people with intellectual disability (ID). This trend reflects a shift in contemporary policy towards entrepreneurship and self-employment as a viable employment option for people with disability in general; a strategy which is intended to promote autonomy and reduce dependence on entitlement-based services as well as to reduce employment disparities and stimulate business and job creation. However, it is not well understood what exactly this means for people with ID involved in social entrepreneurial ventures. This research approached the issue by conducting dyadic interviews to explore the motivations of people with ID who are participating and supported in social entrepreneurship—“why they act.” In exploring these motivations, this article investigates push-pull factors, the role of the social mission, and how support influences motivation.

In this study, we describe the characterization and validation of a diverse panel of fully human CD3-binding antibodies, including hundreds of human and cyno cross-reactive binders. We used two proof-of-concept TCE targets to demonstrate that this panel streamlines CD3 T-cell engager (TCE) development, enabling identification of optimal tumor cell-killing and cytokine-release profiles. CD3 TCEs have potential to be powerful cancer treatments, but the small number of available CD3-binding antibodies and limited multispecific engineering technologies have been barriers to development. Identifying TCEs that balance anti-tumor potency with potential toxicities, such as cytokine release syndrome, requires simultaneous tuning of both the CD3- and tumor-binding arms. Pairs of antibodies that achieve this balance are rare, creating a need for diverse panels of developable antibodies that can be combined and tested to identify optimal clinical candidates. To streamline TCE development, we discovered a diverse panel of CD3-binding antibodies. We screened over 5 million single cells from humanized mice and identified 585 unique CD3-specific antibody sequences. Of these, over 170 were identified as cross-reactive to human and cyno CD3 in primary screening. We then used high-throughput characterization to curate a panel of diverse and developable antibodies. We found a wide range of CD3εδ and CD3εγ binding specificities, affinities, and kinetics. Epitope binning analysis revealed multiple bins containing human and cyno cross-reactive binders, some of which are distinct from previously described cross-reactive antibodies, such as SP34-2. We assessed their biophysical properties and identified antibodies with good developability properties, including high thermal stability and low hydrophobicity, self-association, polyspecificity, and aggregation. To validate these antibodies, we used OrthoMab™ to generate proof-of-concept TCE panels with fixed tumor-binding arms. We identified CD3 x EGFR TCEs with high potency, low cytokine release, functional cross-reactivity in a cyno T cell-mediated tumor killing assay, and good pharmacokinetic properties in Tg32 mice. A second proof-of-concept CD3 x PSMA panel further validated our antibodies in bispecific formats. Together, these studies demonstrate that starting with diverse CD3-binding antibodies streamlines identification of developable TCEs with optimal potency and cytokine release. We leveraged data from our extensive characterization of CD3-binding antibodies in mono- and bispecific formats to develop a strategy for down-selection and pairing of CD3- and tumor-binding antibodies, and a high-throughput method for analysis of resulting TCEs. By categorizing antibodies based on functional properties, we are able to rapidly pinpoint optimal potential clinical candidates for specific tumor targets. Citation Format: Juntao (Matt) Mai, Kate Caldwell, Lindsay DeVorkin, Grace P. Leung, Karine Herve, Yuri Hwang, Cristina Faralla, Wei Wei, Emma Lathouwers, Valentine de Puyraimond, Lauren Clifford, Rhys S. Chappell, Stefan Hannie, Katherine J. Lam, Harveer Dhupar, Tran N. Tran, Melissa Cid, Lena M. Bolten, Tova Pinsky, Ping Xiang, Courteney Lai, Ahn Lee, Vivian Z. Li, Patrick Chan, Jasmine Chin, Steve Booth, Amy C. Lee, Stephanie Masterman, Sherie Duncan, Aaron Yamniuk, Kush Dalal, Tim M. Jacobs, Raffi Tonikian, Bryan C. Barnhart. Identifying T-cell engagers with optimal potency and cytokine-release profiles with a diverse panel of CD3-binding antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1886.

Social entrepreneurship is a growing trend, reflecting a shift in contemporary policy towards entrepreneurship as viable employment option for people with intellectual disability (ID). Entrepreneurship is intended to promote autonomy, reduce dependence on entitlement-based services, and reduce employment disparities while stimulating business and job creation. It is not well understood what this means for people with ID involved in social entrepreneurship. Dyadic interviews were conducted with people with ID participating in social entrepreneurship (n = 7) as well as their key support person (n = 7). Interviews focused on understanding outcomes in social entrepreneurship for people with ID, or “what happens when they act.” In particular, this article explores perceptions of profit/self-sufficiency, growth, and social innovation to challenge how outcomes have been traditionally assessed.

Bispecific antibodies that redirect cancer-killing T cells towards tumors are promising next-generation cancer therapies. While there are hundreds of T cell engagers (TCEs) in development, there is only one approved and marketed CD3-binding TCE. The high rate of attrition is largely attributable to dose-limiting toxicities, including cytokine release syndrome, due in part to the small pool of high affinity CD3-binding antibodies that are commonly used. The discovery of safe and effective TCEs is limited because diverse panels of parental CD3 antibodies are hard to produce, the pairing of parentals is hard to perfect, and the sheer complexity and volume of data is hard to action. In this study, we will present a panel of functionally diverse, fully human CD3-binding parental antibodies. We will present data characterizing the diversity of our panel across multiple parameters, including sequence diversity, CD3 affinity, epitope binding, T cell activation, cytokine release, and tumor cell killing. Using OrthoMab࣪, our clinically-validated bispecific engineering platform, allows this panel to be tested with a series of tumor-associated antigens (TAAs) in a matrix format. Results from high-throughput production and characterization of bispecific antibodies will be presented. These multidimensional datasets of TCE composition and function allow for the identification of pairs that are optimal candidates for clinical development. This work will show how the diversity of our CD3-binding panel, combined with a robust bispecific protein engineering technology, can be used to quickly assess large and diverse TAA-binding panels discovered through our technology stack. An integrated workflow that doubles the data with diverse panels of parentals, assembles stable, safe, and manufacturable TCEs, and visualizes multidimensional datasets are critical to successfully identifying lead therapeutic candidates to bring the next generation of cancer therapies to patients sooner. Citation Format: Lindsay DeVorkin, Tim M. Jacobs, Raffi Tonikian, Karine Hervé, Kate Caldwell, Yuri Hwang, Cristina Faralla, Wei Wei, Katherine J. Lam, Harveer Dhupar, Tran NT Tran, Melissa Cid, Lena M. Bolten, Tova Pinsky, Kush Dalal, Kevin A. Heyries, Bryan C. Barnhart. Redirecting T cells to tumor targets with functionally diverse CD3-binding antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 312.

One of the driving structural requirements of the Habitable Exo-Planet (HabEx) telescope is to maintain Line Of Sight (LOS) stability between the Primary Mirror (PM) and Secondary Mirror (SM) of ≤ 5 mas. Dynamic analyses of two configurations of a proposed (HabEx) 4 meter off-axis telescope structure were performed to predict effects of jitter on primary/secondary mirror alignment. The dynamic disturbance used as the forcing function was the James Webb Space Telescope reaction wheel assembly vibration emission specification level. The objective of these analyses was to predict "order-of-magnitude" performance for various structural configurations which will roll into efforts to define the HabEx structural design's global architecture. Two variations of the basic architectural design were analyzed. Relative motion between the PM and the SM for each design configuration are reported.

The current economic climate demands more innovative approaches to increasing labor market participation for people with disabilities. Social entrepreneurship (SE) offers one alternative employment pathway. However, little is known about the broader factors influencing SE for people with disabilities. Using empirical data from focus groups comprised of social entrepreneurs with disabilities and interviews with key stakeholders working in the fields of policy, disability, and business, this research frames its analysis in the intersection of disability studies and entrepreneurship to explore which factors influence the potential for SE to provide equal participation opportunities for people with disabilities in the labor market. Findings suggest that further consideration of political–economic and socio-cultural factors is needed if we are to better understand the potential of SE for people with disabilities.

Dyadic interviewing is a qualitative approach that recognizes there exists an interdependent relationship between individuals, embracing this phenomenon as a source of information rather than attempting to control for it. Informed by a Critical Disability Studies ideology, this dyadic interview technique has been adapted to address some of the difficulties that present when conducting interviews with individuals with intellectual disabilities. The interview structure consists of a dyad that includes the individual with intellectual disability and the person they identify as their key support person. Currently, researchers have embraced dyadic interviewing as a method of triangulation. However, it also has potential to be used as an important method of accommodation for people with intellectual disability that promotes choice and self-determination in research participation.

BACKGROUND: Policymakers in the United States continue to face challenges in implementing effective strategies to encourage people with disabilities receiving disability benefits to participate in the labor market. Ticket to Work is one such strategy that has undergone considerable scrutiny. However, the experience of people with disabilities within welfare reform is an area that has been under-researched. OBJECTIVE: To explore how this contentious issue affects the provision of Vocational Rehabilitation services. Following the implementation of Ticket to Work, does workfare policy allow people with disabilities to pursue full and equal participation in the labor market, and do they have equality of opportunity to achieve employment? METHODS: This research takes a qualitative approach to social policy, using empirical data from focus groups with people with disabilities and interviews with policymakers, employment service providers and employers. RESULTS: Three themes emerged from an analysis of data framed within the United Nations Convention on the Rights of Persons with Disabilities in relation to disability rights and workfare policy: the rights of people with disabilities; the expectations of people with disabilities; and the practices associated with policy reform. The findings suggest that a collaboration of government actors, community organizations and the business community is necessary in order to achieve human rights.

Social entrepreneurship has been gaining increasing attention as a possible employment strategy for people with dis- abilities. However, little is known about the experiences of social entrepreneurs with disabilities in relation to their resources needs, opportunities for participation, and barriers they encounter. Further, little is understood about how social entrepreneurship differs from self-employment or forms of commercial entrepreneurship. The findings included herein are representative of the first empirical research integrating the fields of disability studies and entrepreneurship studies to explore social entrepreneurship among people with disabilities through interviews with key stakeholders working in the field (n = 19) and focus groups with social entrepreneurs with disabilities themselves (n = 27). Three themes emerged from this qualitative research that hold particular impor- tance to policymakers and professionals working in the field of vocational rehabilitation: 1) education, training and information; 2) finance, funding and asset development; 3) networking and supports. The findings demonstrate that social entrepreneurship can be an effective model of employment but is currently underutilized. With additional investment, it can offer a meaningful way for people with disabilities to participate in the labor market and complement existing strategies in competitive and customized employment to promote choice and self-determination.

Introduction In brachytherapy for cervix cancer, doses to organs at risk (OARs) are traditionally calculated using the ICRU-38 point doses to rectum and bladder. Three-dimensional image-guided brachytherapy allows assessment of OAR dose with dose volume histograms (DVHs). The purpose of this study was to analyse the correlation between DVHs and ICRU point doses. Methods Using the PLATO™ planning system, the bladder, rectum and sigmoid were retrospectively contoured on 62 CT datasets for 20 patients treated with definitive radiotherapy. The median external beam radiotherapy dose was 45 Gy. Brachytherapy was delivered using a CT-MRI compatible tandem and ovoids to a median dose of 24 Gy in three fractions. DVHs were calculated, and the minimum dose to 2 cc of tissue receiving the highest dose (D(2cc) ) was recorded and compared with the ICRU point doses (D(ICRU) ). Results The mean rectal D(ICRU) was 4.01 Gy compared with D(2cc) of 4.28 Gy. The mean bladder D(ICRU) was 6.74 Gy compared with D(2cc) of 8.65 Gy. The mean sigmoid D(2cc) was 4.58 Gy. The mean dose ratios (D(2cc) /D(ICRU) ) were 1.08 for rectum and 1.39 for bladder. D(ICRU) correlated with D(2cc) for rectum (r = 0.76, P = 0.001) and for bladder (r = 0.78, P = 0.01). Conclusion OAR doses assessed by DVH criteria were higher than ICRU point doses. The significant correlation between D(2cc) and D(ICRU) has allowed us to set DVH dose constraints for CT-based brachytherapy and thus begin the transition from two-dimensional to three-dimensional image-guided brachytherapy planning.

The Americans with Disabilities Act (ADA, 1990) is the cornerstone of civil rights policy for people with disabilities. Although enforced through the justice system, the legacy of the ADA transcends well beyond its legal ramifications. The policy’s framework and the rhetoric of Disability Rights suggest both an embrace of the spirit and the letter of the law, or promulgating both legislative and cultural change to ensure that the rights of people with disabilities are met. In attempting to understand how and if such change has happened, researchers have gathered extensive evidence since 1990. Much of this research evidence, however, remains fragmented, under-utilized, and at times inconclusive. This article presents the results of a rapid evidence review of a sample of such research that is crucial to understand the ADA’s progress. The study examines evidence about the ADA’s influence on knowledge, attitudes and perceptions about employment of people with disabilities. The research illustrates the importance of moving beyond the law to incorporate changes in knowledge about the law, perceptions of employability, and workplace culture.&nbsp

Entrepreneurship has been promoted as an innovative strategy to address the employment of people with disabilities. Research has predominantly focused on the self-sufficiency aspect without fully integrating entrepreneurship literature in the areas of theory, systems change, and demonstration projects. Subsequently there are gaps in services, policies, and research in this field that, in turn, have limited our understanding of the support needs and barriers or facilitators of entrepreneurs with disabilities. A thorough analysis of the literature in these areas led to the development of two core concepts that need to be addressed in integrating entrepreneurship into disability employment research and policy: clarity in operational definitions and better disability statistics and outcome measures. This article interrogates existing research and policy efforts in this regard to argue for a necessary shift in the field from focusing on entrepreneurship as self-sufficiency to understanding entrepreneurship as innovation.

Contemporary policy encourages self-employment and entrepreneurship as a vehicle for empowerment and self-sufficiency among people with disabilities. However, such encouragement raises important citizenship questions concerning the participation of people with intellectual and developmental disabilities (IDD). As an innovative strategy for addressing pressing social and economic problems, “social entrepreneurship” has become a phrase that is gaining momentum in the IDD community—one that carries with it a very distinct history. Although social entrepreneurship holds the potential to be an empowering source of job creation and social innovation, it also has the potential to be used to further disenfranchise this marginalized population. It is crucial that in moving forward society takes care not to perpetuate existing models of oppression, particularly in regard to the social and economic participation of people with IDD. The conceptual tools addressed in this article can inform the way that researchers, policymakers, and practitioners approach complex issues, such as social entrepreneurship, to improve communication among disciplines while retaining an integral focus on rights and social justice by framing this issue within citizenship theory.

The intersection of theories of disability and bisexuality is unexplored, yet both are identities rendered in/visible by paternalistic environments where individual and political identities are defined by oppositional binaries and vulnerable to compulsory citizenship. The development of such identities can be better understood by using a bisexual approach to inform theories of disability and a disability approach to inform theories of sexuality inclusive of bisexuality. Common themes that emerge center around issues of choice, fluidity of identity, the phenomena of “coming out” and “passing,” and limitations to citizenship attendant to in/visible identities. Disability studies can provide a non-normative discursive space within which such identity issues may be addressed critically. Further, this article hopes to interject a bisexual perspective in discussions concerning applications of queer theory in disability studies.

Background. Sensory deficits are commonly reported following the resection of spinal cord tumours. The use of transcutaneous electrical nerve stimulation (TENS) as augmented sensory input is described in the research literature but rarely in the clinical literature. Functional electrical stimulation (FES) is used for people with motor impairments rather than sensory impairments. Method and results. This case report describes the use of TENS and FES for a patient with severe sensory loss and mild weakness in the right leg following the removal of an intramedullary spinal cord tumour. The patient was able to walk more quickly and more confidently when using TENS and FES in combination. She consistently reported greater benefits from TENS alone compared to FES alone and continued to use TENS delivered via a sock electrode at six months after surgery. Conclusion. The use of TENS as a sensory stimulus was an invaluable component of this patient's treatment, allowing her to engage in a more challenging balance and gait programme at an earlier stage in her rehabilitation. Combining FES with TENS was also useful and allowed treatment to address motor and sensory impairments concurrently during functional activity. Copyright © 2009 John Wiley & Sons, Ltd.