Building Capacity of Librarians for Knowledge and Skill Development: A Case Study of Nine Institutions of the Consortium for Advanced Research Training in Africa (CARTA)

Librarians have an important part to play in supporting research, training and developing the knowledge economies of nations. The changing roles of librarians and the attendant new skills and knowledge required to play these roles are a major challenge for libraries and librarians in developing countries, especially those in Africa. To meet this challenge, the Consortium for Advanced Research Training in Africa (CARTA) seeks to promote development through advanced research training. In achieving this vision, librarians need to be empowered with knowledge and skills required to support teaching, learning and research in the continent. This is being implemented through the Consortium of CARTA Libraries (CCL), an alliance under CARTA, that aims to strengthen capacity and promote collaboration among librarians and libraries from CARTA institutions

Identifying quasi-experimental studies to inform systematic reviews

OBJECTIVE: This paper reviews the available evidence and guidance on methods to identify reports of quasi-experimental (QE) studies to inform systematic reviews of health care, public health, international development, education, crime and justice, and social welfare. STUDY DESIGN AND SETTING: Research, guidance and examples of search strategies were identified by searching a range of databases, key guidance documents, selected reviews, conference proceedings and personal communication. Current practice and research evidence were summarised. RESULTS: 4914 records were retrieved by database searches and additional documents were obtained by other searches. QE studies are challenging to identify efficiently because they have no standardized nomenclature and may be indexed in various ways. Reliable search filters are not available. There is a lack of specific resources devoted to collecting QE studies and little evidence on where best to search. CONCLUSION: Searches to identify QE studies should search a range of resources and, until indexing improves, use strategies that focus on the topic rather than the study design. Better definitions, better indexing in databases, prospective registers and reporting guidance are required to improve the retrieval of QE studies and to promote SRs of what works based on the evidence from such studies

Evidence gap map of performance measurement and management in primary care delivery systems in low- and middle-income countries – Study protocol [version 1; referees: 2 approved]

Background. For the last two decades there has been growing interest in governmental and global health stakeholders about the role that performance measurement and management systems can play for the production of high-quality and safely delivered primary care services. Despite recognition and interest, the gaps in evidence in this field of research and practice in low- and middle-income countries remain poorly characterized. This study will develop an evidence gap map in the area of performance management in primary care delivery systems in low- and middle-income countries. Methods. The evidence gap map will follow the methodology developed by 3Ie, the International Initiative for Impact Evaluation, to systematically map evidence and research gaps. The process starts with the development of the scope by creating an evidence-informed framework that helps identify the interventions and outcomes of relevance as well as help define inclusion and exclusion criteria. A search strategy is then developed to guide the systematic search of the literature, covering the following databases: Medline (Ovid), Embase (Ovid), CAB Global Health (Ovid), CINAHL (Ebsco), Cochrane Library, Scopus (Elsevier), and Econlit (Ovid). Sources of grey literature are also searched. Studies that meet the inclusion criteria are systematically coded, extracting data on intervention, outcome, measures, context, geography, equity, and study design. Systematic reviews are also critically appraised using an existing standard checklist. Impact evaluations are not appraised but will be coded according to study design. The process of map-building ends with the creation of an evidence gap map graphic that displays the available evidence according to the intervention and outcome framework of interest. Discussion. Applications arising from the evidence map will be discussed in a separate paper that will summarize findings and make recommendations for the development of a prioritized research agenda

Discovery of a Cushing’s syndrome protein kinase A mutant that biases signaling through type I AKAPs

Adrenal Cushing’s syndrome is a disease of cortisol hypersecretion often caused by mutations in protein kinase A catalytic subunit (PKAc). Using a personalized medicine screening platform, we discovered a Cushing’s driver mutation, PKAc-W196G, in ~20% of patient samples analyzed. Proximity proteomics and photokinetic imaging reveal that PKAc W196G is unexpectedly distinct from other described Cushing’s variants, exhibiting retained association with type I regulatory subunits (RI) and their corresponding A kinase anchoring proteins (AKAPs). Molecular dynamics simulations predict that substitution of tryptophan-196 with glycine creates a 653–cubic angstrom cleft between the catalytic core of PKAc W196G and type II regulatory subunits (RII), but only a 395–cubic angstrom cleft with RI. Endocrine measurements show that overexpression of RIα or redistribution of PKAc W196G via AKAP recruitment counteracts stress hormone overproduction. We conclude that a W196G mutation in the kinase catalytic core skews R subunit selectivity and biases AKAP association to drive Cushing’s syndrome. </jats:p

Strengthening women's empowerment and gender equality in fragile contexts towards peaceful and inclusive societies: A systematic review and meta-analysis

Background Across the globe, gender disparities still exist with regard to equitable access to resources, participation in decision-making processes, and gender and sexual-based violence. This is particularly true in fragile and conflict-affected settings, where women and girls are affected by both fragility and conflict in unique ways. While women have been acknowledged as key actors in peace processes and post-conflict reconstruction (e.g., through the United Nations Security Council Resolution 1325 and the Women, Peace and Security Agenda) evidence on the effectiveness of gender-specific and gender-transformative interventions to improve women's empowerment in fragile and conflict-affected states and situations (FCAS) remains understudied. Objectives The purpose of this review was to synthesize the body of evidence around gender-specific and gender-transformative interventions aimed at improving women's empowerment in fragile and conflict-affected settings with high levels of gender inequality. We also aimed to identify barriers and facilitators that could affect the effectiveness of these interventions and to provide implications for policy, practice and research designs within the field of transitional aid. Methods We searched for and screened over 100,000 experimental and quasi-experimental studies focused on FCAS at the individual and community levels. We used standard methodological procedures outlined by the Campbell Collaboration for the data collection and analysis, including quantitative and qualitative analyses, and completed the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology to assess the certainty around each body of evidence. Results We identified 104 impact evaluations (75% randomised controlled trials) assessing the effects of 14 different types of interventions in FCAS. About 28% of included studies were assessed as having a high risk of bias (45% among quasi-experimental designs). Interventions supporting women's empowerment and gender equality in FCAS produced positive effects on the outcomes related to the primary focus of the intervention. There are no significant negative effects of any included interventions. However, we observe smaller effects on behavioural outcomes further along the causal chain of empowerment. Qualitative syntheses indicated that gender norms and practices are potential barriers to intervention effectiveness, while working with local powers and institutions can facilitate the uptake and legitimacy of interventions. Conclusions We observe gaps of rigorous evidence in certain regions (notably MENA and Latin America) and in interventions specifically targeting women as actors of peacebuilding. Gender norms and practices are important elements to consider in programme design and implementation to maximise potential benefits: focusing on empowerment only might not be enough in the absence of targeting the restrictive gender norms and practices that may undermine intervention effectiveness. Lastly, programme designers and implementation should consider explicitly targeting specific empowerment outcomes, promoting social capital and exchange, and tailoring the intervention components to the desired empowerment-related outcomes

Mechanism of glycogen synthase inactivation and interaction with glycogenin

Glycogen is the major glucose reserve in eukaryotes, and defects in glycogen metabolism and structure lead to disease. Glycogenesis involves interaction of glycogenin (GN) with glycogen synthase (GS), where GS is activated by glucose-6-phosphate (G6P) and inactivated by phosphorylation. We describe the 2.6 Å resolution cryo-EM structure of phosphorylated human GS revealing an autoinhibited GS tetramer flanked by two GN dimers. Phosphorylated N- and C-termini from two GS protomers converge near the G6P-binding pocket and buttress against GS regulatory helices. This keeps GS in an inactive conformation mediated by phospho-Ser641 interactions with a composite “arginine cradle”. Structure-guided mutagenesis perturbing interactions with phosphorylated tails led to increased basal/unstimulated GS activity. We propose that multivalent phosphorylation supports GS autoinhibition through interactions from a dynamic “spike” region, allowing a tuneable rheostat for regulating GS activity. This work therefore provides insights into glycogen synthesis regulation and facilitates studies of glycogen-related diseases

Mps1 Phosphorylates Its N-Terminal Extension to Relieve Autoinhibition and Activate the Spindle Assembly Checkpoint

Monopolar spindle 1 (Mps1) is a conserved apical kinase in the spindle assembly checkpoint (SAC) that ensures accurate segregation of chromosomes during mitosis. Mps1 undergoes extensive auto- and transphosphorylation, but the regulatory and functional consequences of these modifications remain unclear. Recent findings highlight the importance of intermolecular interactions between the N-terminal extension (NTE) of Mps1 and the Hec1 subunit of the NDC80 complex, which control Mps1 localization at kinetochores and activation of the SAC. Whether the NTE regulates other mitotic functions of Mps1 remains unknown. Here, we report that phosphorylation within the NTE contributes to Mps1 activation through relief of catalytic autoinhibition that is mediated by the NTE itself. Moreover, we find that this regulatory NTE function is independent of its role in Mps1 kinetochore recruitment. We demonstrate that the NTE autoinhibitory mechanism impinges most strongly on Mps1-dependent SAC functions and propose that Mps1 activation likely occurs sequentially through dimerization of a “prone-to-autophosphorylate” Mps1 conformer followed by autophosphorylation of the NTE prior to maximal kinase activation segment trans-autophosphorylation. Our observations underline the importance of autoregulated Mps1 activity in generation and maintenance of a robust SAC in human cells