Setting research priorities for prevention and response to child marriage in communities in the Arab region: findings from a multi-stage Delphi study involving practitioners across the region.

Globally, more than 12 million girls under the age of 18 are forced to marry every year. Progress on ending child marriage in the Arab region is slowing, and risks being reversed, due to an increase in conflict-affected populations and widespread economic crisis. The aim of this paper is to consider the research priorities across the region to inform effective and accelerated child marriage prevention and response programming within the Arab region. Seventy-three specialists supporting child marriage prevention and response programming in the Arab region engaged with up to three phases of an online Delphi consultation process on research gaps and the research environment between July 2019 and December 2021. Proposals of research gaps were elicited, reviewed, and rated by participants to confirm a shared learning agenda. Participants identified 50 different research gaps across 7 main areas, reaching a high level of consensus support for 23 of 50 statements. Clear consensus was reached in relation to an increased need to produce and use evidence to support programme development, and further research on specific drivers and consequences of child marriage. The least consensus was found in relation to how research can inform prevention and response efforts within the law and legal system. The results provide the foundation of a child marriage research agenda for the Arab region which takes into account regional distinctiveness and builds on the global momentum for child marriage research. Mechanisms are in place to do this through the Regional Action Forum, and other networks across the region.

Multiagency safeguarding arrangements during and beyond the Covid-19 pandemic: Identifying shared learning.

Measures to combat transmission of the coronavirus presented unprecedented challenges for safeguarding and child protection practice, including through withdrawal of routine opportunities to observe and engage with children and families and disruption of systems for inter-agency communication and coordination. This article reports on a two-stage study designed to identify shared learning from adaptations to professional practice in response to the measures. Interviews with 67 London-based senior safeguarding leads from seven professional groups undertaken during the summer of 2020 informed an England-wide survey to similar groups in February-March 2021. SPSS was used to analyse 417 responses, which were supplemented by answers to open questions. Findings are reported using the six practice themes which the Child Safeguarding Practice Review Panel expects to inform shared learning to improve safeguarding at national and local levels. The study revealed the formidable barriers facing professionals in understanding the changing environments in which children were living and in identifying and assessing new or altered risks due to the pandemic; steps taken to respond to changing risks and to keep in touch and re-engage families; strategies to support critical thinking and challenge among professionals working under unprecedented pressure; and opportunities for enhanced multiagency working and inter-agency collaboration.

Resurrecting the interval of need concept to improve dialogue between researchers, policymakers, and social care practitioners.

Academics, social care practitioners, and policymakers speak different languages. If academic research is to have an impact on society, it must be understandable and convincing to the end users. We argue that the conceptualisation of social care "need" is different among these stakeholders, leading to poor communication between them. Academics should use concepts that have more meaning to practitioners. We propose resurrecting a little-used concept from the 1970s, "interval of need", to help to bridge this gap. The interval of need concept identifies how often people require help, supplementing the usual data about types of tasks where assistance is needed. The history of the concept is described, followed by a test of its usefulness for today's researchers by applying it to data from the English Longitudinal Study of Ageing. An updated version of interval of need is proposed. Validation checks were conducted against mortality data, and through conceptual validation from a social work practitioner. The nature of the dataset limited comparability with previous studies. However, we conclude that the interval of need concept has promising scope to enhance communication of research findings, potentially leading to improved outcomes for service users. This paper strives to mark a turning point in the language and analysis of social care, ensuring that academic investigation in this field is convincing and clear to practitioners and policymakers.

Understanding processes of risk and protection that shape the sexual and reproductive health of young women affected by conflict: the price of protection.

BACKGROUND: It is assumed that knowing what puts young women at risk of poor sexual health outcomes and, in turn, what protects them against these outcomes, will enable greater targeted protection as well as help in designing more effective programmes. Accordingly, efforts have been directed towards mapping risk and protective factors onto general ecological frameworks, but these currently do not take into account the context of modern armed conflict. A literature overview approach was used to identify SRH related risk and protective factors specifically for young women affected by modern armed conflict. PROCESSES OF RISK AND PROTECTION: A range of keywords were used to identify academic articles which explored the sexual and reproductive health needs of young women affected by modern armed conflict. Selected articles were read to identify risk and protective factors in relation to sexual and reproductive health. While no articles explicitly identified 'risk' or 'protective' factors, we were able to extrapolate these through a thorough engagement with the text. However, we found that it was difficult to identify factors as either 'risky' or 'protective', with many having the capacity to be both risky and protective (i.e. refugee camps or family). Therefore, using an ecological model, six environments that impact upon young women's lives in contexts of modern armed conflict are used to illustrate the dynamic and complex operation of risk and protection - highlighting processes of protection and the 'trade-offs' between risks. CONCLUSION: We conclude that there are no simple formulaic risk/protection patterns to be applied in every conflict and post-conflict context. Instead, there needs to be greater recognition of the 'processes' of protection, including the role of 'trade-offs' (what we term as 'protection at a price'), in order to further effective policy and practical responses to improve sexual and reproductive health outcomes during or following armed conflict. Focus on specific 'factors' (such as 'female headed household') takes attention away from the processes through which factors manifest themselves and which often determine whether the factor will later be considered 'risk inducing' or protective.

Bortezomib disrupts tumour-dendritic cell interactions in myeloma and lymphoma: therapeutic implications.

Recent studies have shown that the interactions between tumour and dendritic cells (DCs) promote clonogenic growth of lymphoproliferative tumours, particularly myeloma. The present study showed that the proteasome inhibitor, bortezomib, disrupts this interaction. Targeting the drug to DCs was required for optimal suppression of tumour growth, including primary myeloma tumour progenitors in clonogenic assays. Bortezomib lead to dose-dependent induction of apoptosis in both myeloid and plasmacytoid DCs, and the sensitivity of DCs to bortezomib was comparable with that of tumour cells. These data suggest that disruption of tumour-DC interactions may contribute to the clinical effects of bortezomib.

Enhancement of clonogenicity of human multiple myeloma by dendritic cells.

Infiltration by dendritic cells (DCs) is a common feature of most human tumors. Prior studies evaluating the interaction of DCs with tumors have focused largely on their immunologic properties (for review see Banchereau, J., and R.M. Steinman. 1998. Nature. 392:245-252). In this study, we show that the clonogenicity of several human tumor cell lines and primary tumor cells from myeloma patients is enhanced by their interactions with DCs. Myeloma cells cultured in the presence of DCs have an altered phenotype with an increased proportion of cells lacking terminal plasma cell differentiation marker CD138. DC-tumor interaction also leads to the up-regulation of B cell lymphoma 6 expression in myeloma cells. Effects of DCs on myeloma cells are inhibited by blockade of the receptor activator of NF-kB (RANK)-RANK ligand and B cell-activating factor-APRIL (a proliferation-inducing ligand)-mediated interactions. Together, these data suggest that tumor-DC interactions may directly impact the biology of human tumors, particularly multiple myeloma, and may be a target for therapeutic intervention.

Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients.

Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes that are implicated in the resistance to pathogens and tumors. Earlier attempts to mobilize NKT cells, specifically, in vivo in humans met with limited success. Here, we evaluated intravenous injection of monocyte-derived mature DCs that were loaded with a synthetic NKT cell ligand, alpha-galactosyl-ceramide (alpha-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of alpha-GalCer-pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of several subsets of NKT cells in all patients; these could be detected for up to 6 mo after vaccination. NKT activation was associated with an increase in serum levels of interleukin-12 p40 and IFN-gamma inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to alpha-GalCer-loaded DCs, but not unpulsed DCs. These data demonstrate the feasibility of sustained expansion of NKT cells in vivo in humans, including patients who have advanced cancer, and suggest that NKT activation might help to boost adaptive T cell immunity in vivo.