Igniting the Spark: Creating Effective Next Generation Boards

For family foundations and a growing number of donor-advised funds, preparing the next generation for involvement brings special concerns -- and exciting opportunities. Succession is reported to be the single most important issue facing family foundations, according to nearly half (48%) of respondents to the Association for Small Foundations 2011 Foundation Operations and Management Report. At the same time, there is a broad range of experience in families with regard to how next generation family members are involved in family philanthropy. According to the National Center for Family Philanthropy's 2011 study, Current Practices in Family Foundations, a near equal number of respondents "strongly agreed" (34%) or "strongly disagreed" (33%) with the statement "next generation members are playing a significant role in the foundation.

“Why Can’t Run ‘Like a Girl’ Also Mean Win The Race?”: Commodity Feminism and Participatory Branding as Forms of Self-Therapy in the Neoliberal Advertising Space

This thesis proposes a critical study of the techniques and motives behind modern commodity feminist advertising, focusing on the appropriation of the “young girl” as a symbol of the feminist cause. This evolving trend in advertising, building upon new movements of empowerment and the recent proliferation of the online feminist space, is shifting the logics of consumption by marketing feminist ideology and activism through consumer purchasing power. By prompting consumers to believe that their purchases can make a significant change, companies are developing brand loyalty in their key marketing demographics by using the image and rhetoric of the “young girl” to tap into a term I call “anti-nostalgia,” a nostalgia whereby women leverage the inherent sentimentality of childhood with a constructive understanding and rejection of the destructively sexist climate they experienced to combat these sociocultural conditions for future generations. Joining theoretical research on branding, user-generated content, and the neoliberal ideology of the consumer-citizen, I argue that these advertising campaigns, coupled with online spaces for public interaction and participation, effectively create channels for their target consumers to contribute to this commodified form of activism. In reality, however, these “feminist” purchases are simply forms of consumer self-therapy in a modern political climate of systemic gender discrimination

Can We Do A Happy Musical Next Time? : Navigating Brechtian Tradition and Satirical Comedy Through Hope\u27s Eyes in Urinetown: The Musical

This thesis proposes a critical study of the theoretical framework of Urinetown, asking the question of whether or not the show is truly a “Brechtian musical,” utilizing the tenets and beliefs of Bertolt Brecht. Set in a quirky, Gotham-like town where you have “to pay to pee” due to a severe drought, Urinetown follows a cast of absurdist characters as they navigate a society plagued by the perils of big business, ecological devastation, and the inequalities of capitalism. While the show appears to make a relevant social commentary, supporting a righteous rebellion to overthrow the evil Urine Good Company, in the end, by proving that revolution does not always succeed, writers, Kotis and Hollman invalidate these commentaries, proving that despite its Brechtian appearance, the show in its textual form is much more simply a comedic parody. However, Pomona College’s production, in which I played Hope Cladwell, takes on a much more severe tone, creating legitimate commentary by replacing many of the comedic, two-dimensional characters with living breathing, realities. In a text traditionally lacking authenticity, I approached Hope Cladwell with the intention of finding strength and satire in an otherwise vapid character

T antigen–specific CD8⁺ T cells associate with PD-1 blockade response in virus-positive Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer primarily induced by Merkel cell polyomavirus, which is driven by the expression of the oncogenic T antigens (T-Ags). Blockade of the programmed cell death protein-1 (PD-1) pathway has shown remarkable response rates, but evidence for therapy-associated T-Ag–specific immune response and therapeutic strategies for the nonresponding fraction are both limited. We tracked T-Ag–reactive CD8+ T cells in peripheral blood of 26 MCC patients under anti-PD1 therapy, using DNA-barcoded pMHC multimers, displaying all peptides from the predicted HLA ligandome of the oncoproteins, covering 33 class I haplotypes. We observed a broad T cell recognition of T-Ags, including identification of 20 T-Ag–derived epitopes we believe to be novel. Broadening of the T-Ag recognition profile and increased T cell frequencies during therapy were strongly associated with clinical response and prolonged progression-free survival. T-Ag–specific T cells could be further boosted and expanded directly from peripheral blood using artificial antigen-presenting scaffolds, even in patients with no detectable T-Ag–specific T cells. These T cells provided strong tumor-rejection capacity while retaining a favorable phenotype for adoptive cell transfer. These findings demonstrate that T-Ag–specific T cells are associated with the clinical outcome to PD-1 blockade and that Ag-presenting scaffolds can be used to boost such responses.</p

TCR-engaging scaffolds selectively expand antigen-specific T-cells with a favorable phenotype for adoptive cell therapy

Background Adoptive cell therapy (ACT) has shown promising results for the treatment of cancer and viral infections. Successful ACT relies on ex vivo expansion of large numbers of desired T-cells with strong cytotoxic capacity and in vivo persistence, which constitutes the greatest challenge to current ACT strategies. Here, in this study, we present a novel technology for ex vivo expansion of antigen-specific T-cells; artificial antigen-presenting scaffolds (Ag-scaffolds) consisting of a dextran-polysaccharide backbone, decorated with combinations of peptide-Major Histocompatibility Complex (pMHC), cytokines and co-stimulatory molecules, enabling coordinated stimulation of antigen-specific T-cells. Methods The capacity of Ag-scaffolds to expand antigen-specific T-cells was explored in ex vivo cultures with peripheral blood mononuclear cells from healthy donors and patients with metastatic melanoma. The resulting T-cell products were assessed for phenotypic and functional characteristics. Results We identified an optimal Ag-scaffold for expansion of T-cells for ACT, carrying pMHC and interleukin-2 (IL-2) and IL-21, with which we efficiently expanded both virus-specific and tumor-specific CD8+ T cells from peripheral blood of healthy donors and patients, respectively. The resulting T-cell products were characterized by a high frequency of antigen-specific cells with high self-renewal capacity, low exhaustion, a multifunctional cytokine profile upon antigen-challenge and superior tumor killing capacity. This demonstrates that the coordinated stimuli provided by an optimized stoichiometry of TCR engaging (pMHC) and stimulatory (cytokine) moieties is essential to obtain desired T-cell characteristics. To generate an 'off-the-shelf' multitargeting Ag-scaffold product of relevance to patients with metastatic melanoma, we identified the 30 most frequently recognized shared HLA-A0201-restricted melanoma epitopes in a cohort of 87 patients. By combining these in an Ag-scaffold product, we were able to expand tumor-specific T-cells from 60-70% of patients with melanoma, yielding a multitargeted T-cell product with up to 25% specific and phenotypically and functionally improved T cells. Conclusions Taken together, the Ag-scaffold represents a promising new technology for selective expansion of antigen-specific CD8+ T cells directly from blood, yielding a highly specific and functionally enhanced T-cell product for ACT.</p

TCR-engaging scaffolds selectively expand antigen-specific T-cells with a favorable phenotype for adoptive cell therapy

Background Adoptive cell therapy (ACT) has shown promising results for the treatment of cancer and viral infections. Successful ACT relies on ex vivo expansion of large numbers of desired T-cells with strong cytotoxic capacity and in vivo persistence, which constitutes the greatest challenge to current ACT strategies. Here, in this study, we present a novel technology for ex vivo expansion of antigen-specific T-cells; artificial antigen-presenting scaffolds (Ag-scaffolds) consisting of a dextran-polysaccharide backbone, decorated with combinations of peptide-Major Histocompatibility Complex (pMHC), cytokines and co-stimulatory molecules, enabling coordinated stimulation of antigen-specific T-cells.Methods The capacity of Ag-scaffolds to expand antigen-specific T-cells was explored in ex vivo cultures with peripheral blood mononuclear cells from healthy donors and patients with metastatic melanoma. The resulting T-cell products were assessed for phenotypic and functional characteristics.Results We identified an optimal Ag-scaffold for expansion of T-cells for ACT, carrying pMHC and interleukin-2 (IL-2) and IL-21, with which we efficiently expanded both virus-specific and tumor-specific CD8+ T cells from peripheral blood of healthy donors and patients, respectively. The resulting T-cell products were characterized by a high frequency of antigen-specific cells with high self-renewal capacity, low exhaustion, a multifunctional cytokine profile upon antigen-challenge and superior tumor killing capacity. This demonstrates that the coordinated stimuli provided by an optimized stoichiometry of TCR engaging (pMHC) and stimulatory (cytokine) moieties is essential to obtain desired T-cell characteristics. To generate an ‘off-the-shelf’ multitargeting Ag-scaffold product of relevance to patients with metastatic melanoma, we identified the 30 most frequently recognized shared HLA-A0201-restricted melanoma epitopes in a cohort of 87 patients. By combining these in an Ag-scaffold product, we were able to expand tumor-specific T-cells from 60–70% of patients with melanoma, yielding a multitargeted T-cell product with up to 25% specific and phenotypically and functionally improved T cells.Conclusions Taken together, the Ag-scaffold represents a promising new technology for selective expansion of antigen-specific CD8+ T cells directly from blood, yielding a highly specific and functionally enhanced T-cell product for ACT

Results of a Randomized Clinical Trial of Speech after Early Neurostimulation in Parkinson's Disease

International audienc

Results of a Randomized Clinical Trial of Speech after Early Neurostimulation in Parkinson's Disease

BackgroundThe EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. ObjectiveThis prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. MethodsSTN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. ResultsOver the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. ConclusionAt this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. (c) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society