Peripheral blood CD34+ cells efficiently engraft human cytokine knock-in mice.

Human CD34+ hematopoietic stem and progenitor cells (HSPCs) can reconstitute a human hemato-lymphoid system when transplanted into immunocompromised mice. Although fetal liver-derived and cord blood-derived CD34+ cells lead to high engraftment levels, engraftment of mobilized, adult donor-derived CD34+ cells has remained poor. We generated so-called MSTRG and MISTRG humanized mice on a Rag2-/-Il2rg-/- background carrying a transgene for human signal regulatory protein α (SIRPα) and human homologs of the cytokine macrophage colony-stimulating factor, thrombopoietin, with or without interleukin-3 and granulocyte-macrophage colony-stimulating factor under murine promoters. Here we transplanted mobilized peripheral blood (PB) CD34+ cells in sublethally irradiated newborn and adult recipients. Human hematopoietic engraftment levels were significantly higher in bone marrow (BM), spleen, and PB in newborn transplanted MSTRG/MISTRG as compared with nonobese diabetic/severe combined immunodeficient Il2rg-/- or human SIRPα-transgenic Rag2-/-Il2rg-/- recipients. Furthermore, newborn transplanted MSTRG/MISTRG mice supported higher engraftment levels of human phenotypically defined HSPCs in BM, T cells in the thymus, and myeloid cells in nonhematopoietic organs such as liver, lung, colon, and skin, approximating the levels in the human system. Similar results were obtained in adult recipient mice. Thus, human cytokine knock-in mice might open new avenues for personalized studies of human pathophysiology of the hematopoietic and immune system in vivo.

Probabilistic cost-benefit analysis of disaster risk management in a development context.

Limited studies have shown that disaster risk management (DRM) can be cost-efficient in a development context. Cost-benefit analysis (CBA) is an evaluation tool to analyse economic efficiency. This research introduces quantitative, stochastic CBA frameworks and applies them in case studies of flood and drought risk reduction in India and Pakistan, while also incorporating projected climate change impacts. DRM interventions are shown to be economically efficient, with integrated approaches more cost-effective and robust than singular interventions. The paper highlights that CBA can be a useful tool if certain issues are considered properly, including: complexities in estimating risk; data dependency of results; negative effects of interventions; and distributional aspects. The design and process of CBA must take into account specific objectives, available information, resources, and the perceptions and needs of stakeholders as transparently as possible. Intervention design and uncertainties should be qualified through dialogue, indicating that process is as important as numerical results.