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IntroductionHematopoietic and endothelial cells are mesoderm-derived lineages that demonstrate a close spatial, temporal, and genetic relationship during vertebrate embryogenesis. 1 These properties have led to the hypothesis that these cell lineages originate from a common precursor, so-called hemangioblasts or hematogenicendothelial cells. 2,3 Mouse embryonic stem cells (mESCs) have been instrumental to define the phenotypic and developmental pathways that regulate endothelial and hematopoietic development. [4][5][6][7][8] For example, blast colony-forming cells (BL-CFCs) are thought to represent the functional equivalent of a common progenitor cell for both endothelial and hematopoietic cells after differentiation of mESCs. 5 Importantly, similar cells with hematoendothelial potential have been identified in the posterior region of the primitive streak in mouse embryos, effectively translating in vitro differentiation from mESCs to in vivo embryonic development. 9 However, recent in vivo lineage tracing studies of the developing yolk sac suggest that other mechanisms may also be involved. 10 Continued studies are therefore needed, especially in a human model system where the relationship between hematopoietic and endothelial cells remains poorly characterized.Several reports of hematopoietic differentiation from human ESCs (hESCs) demonstrate that similar strategies used to study development of hematopoietic and endothelial lineages from mESCs can be transposed to the hESC system. [11][12][13][14][15][16] This allows analysis of early cell fate specifications of endothelial and hematopoietic cells in a model system that is more directly relevant to human development. As with mESCs, there are 2 routine methods used to facilitate differentiation of hESCs: embryoid body (EB) formation and stromal cell coculture. Although the general kinetics of differentiation suggests a conserved pattern for development of endothelial and hematopoietic precursors between different methods of hESC differentiation, there are differences in the requirement for defined growth factors for development of hematopoietic precursors when hESCs are cocultured with stromal cells compared with EB differentiation. 17 One study identified progenitor cells within hESC-derived EBs that express CD31, Flk1, and VE-cadherin but not CD45 (termed CD45 neg PFV cells), after approximately 7 to 10 days of differentiation, capable of generating both endothelial and hematopoietic cells. 13 A similar study also identified hematogenic potential of endothelial cells from CD34 ϩ CD31 ϩ CD45 Ϫ human EB-derived cells also after 10 days of differentiation. 14 Another recent report demonstrates development of a cell population during EB-mediated differentiation of hESCs that express Flk1 (also termed KDR or VEGF-R2) and generate BL-CFCs similar to what has been observed for mESCs. 15 Development of these human hemangioblast cells was observed earlier in the culture and was dependent on presence of bFGF, VEGF, and BMP4 during EB differentiation. 15 Yet another gr...

While CRS + HIPEC has led to an improved survival for patients with MPM compared to historic data, heterogeneity of studies precludes generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may infer survival benefit.

Maternal antiretroviral therapy (ART) is a critical intervention in the prevention-of-mother-to child transmission (PMTCT) of HIV. In South Africa, many HIV-infected pregnant women commence ART late in pregnancy, and as a result, the duration of ART prior to delivery is often insufficient to prevent vertical transmission. To address this, we designed an intervention for the rapid initiation of ART in pregnancy (RAP), where patient's ART preparation occurred during rather than before treatment commencement. Here we report on the acceptability and the challenges of the RAP programme. We conducted 7 key informant and 27 semi-structured interviews with RAP participants. Participants were purposefully selected based on ART-eligibility and stage in the pregnancy to post-partum continuum. Interviews were conducted in participants' home language by trained fieldworkers, with key informant interviews conducted by the study investigators. The data were analysed using a framework analysis approach. Rapid initiation in pregnancy was acceptable to the majority of programme participants and protection of the woman's unborn child was the primary motivation for starting treatment. The key barrier was the limited time to accept the dual challenges of being diagnosed HIV-positive and eligible for life-long ART. Truncated time also limited the opportunity for disclosure to others. Despite these and other barriers, most women found the benefits of rapid ART commencement outweighed the challenges, with 91% of women initiated onto ART starting the same day treatment eligibility was determined. Many participants and key informants identified the importance of counseling and the need to make an informed, independent choice on the timing of ART initiation, based on individual circumstances. Acceptance of ART-eligibility improved with time on the programme, however, as women's principal reason for initiating ART was protection of the unborn child, monitoring and supporting adherence during the post-partum period will be critical.

Background:The importance of youth engagement in designing, implementing and evaluating programs has garnered more attention as international initiatives seek to address the HIV crisis among this population. Adolescents, however, are not often included in HIV implementation science research and have not had opportunities to contribute to the development of HIV-related research agendas. Project Supporting Operational AIDS Research (SOAR), a United States Agency for International Development-funded global operations research project, involved youth living with HIV in a meeting to develop a strategic implementation science research agenda to improve adolescent HIV care continuum outcomes, including HIV testing and counseling (HTC) and linkage to care.Methods:Project SOAR convened a 2-day meeting of 50 experts, including four youth living with HIV. Participants examined the literature, developed research questions, and voted to prioritize these questions for the implementation science research agenda. This article presents the process of involving youth, how they shaped the course of discussions, and the resulting priority research gaps identified at the meeting.Results:Youth participation influenced working group discussions and the development of the implementation science agenda. Research gaps identified included how to engage vulnerable adolescents, determining the role that stigma, peers, and self-testing have in shaping adolescent HTC behaviors, and examining the costs of different HTC and linkage to care strategies.Conclusion:The meeting participants developed the research agenda to guide future implementation science research to improve HIV outcomes among adolescents in sub-Saharan Africa. This process highlighted the importance of youth in shaping implementation science research agendas and the need for greater youth engagement.

While dedicated adolescent SRHS might best meet the needs of young people in SA, the study suggests that failing this, existing SRHS should be more responsive to adolescent use. Innovations such as mobile outreach services, self-testing and flexible hours will help SRHS respond to adolescents' needs.

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This pilot programme provides evidence that rapid ART initiation in pregnancy is safe, feasible and effective in reducing PMTCT. Further follow-up is required to monitor long-term outcomes.