The Generational Journey of Racial Reconciliation: A Call for Tender Hearts and Continuing Conversation Through a Servant-First Life of Leadership

In the polarized context of today’s society ideological differences on how to address issues of race funnel the angst from riot-stricken streets into school board meetings, sour social media posts, and cancel both careers and friendships. This article examines the critical critique of what has been called third wave anti-racism contrasting this critique with foundational tenants of critical race theory. Servant-leadership is presented as a preferred alternative leading to continuing conversation with tender hearts, which choose to remember the abuses of the past while seeking renewed reconciliation for the sake of future generations

Serendipity in Non-Profit Founding and the Healing Response of Two Servant-Leaders to Crises of Migration

This article explores the intersection of non-profit founding with elements of servant-leadership. Drawing upon current research in social entrepreneurship and non-profit founding, the article reflects on these in light of the stories of two selfless individuals, Varian Fry and Enrique Morones, whose lives of servanthood spawned the founding of two influential organizations: the Emergency Rescue Committee (ERC) and the Border Angels. While sharing the stories of these organizations, and of their founding, this article highlights issues of immigration offering a healing perspective through five themes of servant-leadership articulated by Robert K. Greenleaf revealed in the lives of these non-profit founders. Along the way, this article introduces concepts of global citizenship as an antidote to fears that stoke nationalistic and isolationist mindsets, which are mindsets both the ERC and the Border Angels sought to overcome

Continuation-Passing C: compiling threads to events through continuations

In this paper, we introduce Continuation Passing C (CPC), a programming language for concurrent systems in which native and cooperative threads are unified and presented to the programmer as a single abstraction. The CPC compiler uses a compilation technique, based on the CPS transform, that yields efficient code and an extremely lightweight representation for contexts. We provide a proof of the correctness of our compilation scheme. We show in particular that lambda-lifting, a common compilation technique for functional languages, is also correct in an imperative language like C, under some conditions enforced by the CPC compiler. The current CPC compiler is mature enough to write substantial programs such as Hekate, a highly concurrent BitTorrent seeder. Our benchmark results show that CPC is as efficient, while using significantly less space, as the most efficient thread libraries available.Comment: Higher-Order and Symbolic Computation (2012). arXiv admin note: substantial text overlap with arXiv:1202.324

Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations

Background: The heterogeneity and tumourigenicity of metastatic melanoma is attributed to a cancer stem cell model, with CD133 considered to be a cancer stem cell marker in melanoma as well as other tumours, but its role has remained controversial. Methods: We iteratively sorted CD133+ and CD133- cells from 3 metastatic melanoma cell lines, and observed tumourigenicity and phenotypic characteristics over 7 generations of serial xeno-transplantation in NOD/SCID mice. Results: We demonstrate that iterative sorting is required to make highly pure populations of CD133+ and CD133- cells from metastatic melanoma, and that these two populations have distinct characteristics not related to the cancer stem cell phenotype. In vitro, gene set enrichment analysis indicated CD133+ cells were related to a proliferative phenotype, whereas CD133- cells were of an invasive phenotype. However, in vivo, serial transplantation of CD133+ and CD133- tumours over 7 generations showed that both populations were equally able to initiate and propagate tumours. Despite this, both populations remained phenotypically distinct, with CD133- cells only able to express CD133 in vivo and not in vitro. Loss of CD133 from the surface of a CD133+ cell was observed in vitro and in vivo, however CD133- cells derived from CD133+ retained the CD133+ phenotype, even in the presence of signals from the tumour microenvironment. Conclusion: We show for the first time the necessity of iterative sorting to isolate pure marker-positive and marker-negative populations for comparative studies, and present evidence that despite CD133+ and CD133- cells being equally tumourigenic, they display distinct phenotypic differences, suggesting CD133 may define a distinct lineage in melanoma

Case report: Partial regression of metastatic squamous cell carcinoma with altered azathioprine dosage after long-term use in renal transplant patient

IntroductionWe report the partial regression of metastatic squamous cell carcinoma (SCC) after reduction of long-term azathioprine therapy while awaiting surgery. The patient was a 69-year-old man with a history of kidney transplantation. Moderately differentiated SCC arising in the anterior neck was initially diagnosed, followed later by poorly differentiated SCC metastases to cervical lymph nodes. Lymph node clearance was performed 28 days after a reduction in azathioprine dosage. The palpable lymph node lesion had noticeably decreased in size at the time of surgery, and subsequent histology only detected 7mm and 0.2mm deposits of poorly differentiated SCC in 2 of 5 level I nodes, and a further 10 reactive nodes from levels II and III. One positive level I and another benign level II/III node, demonstrated necrosis, histiocytic infiltration and fibrosis, interpreted as features of regression. Hence, we investigated the role of immune cells in the partial regression of metastatic SCC after reduction of long-term azathioprine therapy while awaiting surgery.MethodsMultispectral immunohistochemistry using custom markers was performed on regions of interest of excised cervical lymph nodes, encompassing the entire SCC deposit and the surrounding adjacent stroma to quantify to number and types of immune cells present.ResultsMultispectral immunohistochemistry revealed the heavy infiltration of activated T cells in the tumour, as well as PD-L1+ antigen-presenting cells in the surrounding adjacent stroma, suggesting an immunologically mediated partial regression.DiscussionWe hypothesize that this reaction was triggered by azathioprine dose reduction. Dose modification of long-term immunosuppressive medications in patients with a transplantation history who later develop SCCs warrants further investigation

Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma.

Group 2 innate lymphoid cells (ILC2s) are essential to maintain tissue homeostasis. In cancer, ILC2s can harbor both pro-tumorigenic and anti-tumorigenic functions, but we know little about their underlying mechanisms or whether they could be clinically relevant or targeted to improve patient outcomes. Here, we found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis. ILC2s are critical producers of the cytokine granulocyte-macrophage colony-stimulating factor, which coordinates the recruitment and activation of eosinophils to enhance antitumor responses. Tumor-infiltrating ILC2s expressed programmed cell death protein-1, which limited their intratumoral accumulation, proliferation and antitumor effector functions. This inhibition could be overcome in vivo by combining interleukin-33-driven ILC2 activation with programmed cell death protein-1 blockade to significantly increase antitumor responses. Together, our results identified ILC2s as a critical immune cell type involved in melanoma immunity and revealed a potential synergistic approach to harness ILC2 function for antitumor immunotherapies

Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk

We examined the relation with birth weight and umbilical cord blood concentrations of haematopoietic stem and progenitor populations in 288 singleton infants. Across the whole range of birth weight, there was a positive relation between birth weight and CD34+CD38− cells, with each 500 g increase in birth weight being associated with a 15.5% higher (95% confidence interval: 1.6–31.3%) cell concentration. CD34+ and CD34+c-kit+ cells had J-shaped relations and CFU-GM cells had a U-shaped relation with birth weight. Among newborns with ⩾3000 g birth weights, concentrations of these cells increased with birth weight, while those below 3000 g had higher stem cell concentrations than the reference category of 3000–3499 g. Adjustment for cord blood plasma insulin-like growth factor-1 levels weakened the stem and progenitor cell–birth weight associations. The positive associations between birth weight and stem cell measurements for term newborns with a normal-to-high birth weight support the stem cell burden hypothesis of cancer risk