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- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Kontos, C, et al.
(författare)
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Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5981-
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Tidskriftsartikel (refereegranskat)abstract
- Targeting a specific chemokine/receptor axis in atherosclerosis remains challenging. Soluble receptor-based strategies are not established for chemokine receptors due to their discontinuous architecture. Macrophage migration-inhibitory factor (MIF) is an atypical chemokine that promotes atherosclerosis through CXC-motif chemokine receptor-4 (CXCR4). However, CXCR4/CXCL12 interactions also mediate atheroprotection. Here, we show that constrained 31-residue-peptides (‘msR4Ms’) designed to mimic the CXCR4-binding site to MIF, selectively bind MIF with nanomolar affinity and block MIF/CXCR4 without affecting CXCL12/CXCR4. We identify msR4M-L1, which blocks MIF- but not CXCL12-elicited CXCR4 vascular cell activities. Its potency compares well with established MIF inhibitors, whereas msR4M-L1 does not interfere with cardioprotective MIF/CD74 signaling. In vivo-administered msR4M-L1 enriches in atherosclerotic plaques, blocks arterial leukocyte adhesion, and inhibits atherosclerosis and inflammation in hyperlipidemic Apoe−/− mice in vivo. Finally, msR4M-L1 binds to MIF in plaques from human carotid-endarterectomy specimens. Together, we establish an engineered GPCR-ectodomain-based mimicry principle that differentiates between disease-exacerbating and -protective pathways and chemokine-selectively interferes with atherosclerosis.
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| 8. |
- Hirons, M., et al.
(författare)
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Illegality and inequity in Ghana's cocoa-forest landscape : How formalization can undermine farmers control and benefits from trees on their farms
- 2018
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Ingår i: Land Use Policy. - : Elsevier BV. - 0264-8377. ; 76, s. 405-413
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Tidskriftsartikel (refereegranskat)abstract
- Schemes to promote sustainable forest management have increasingly focused on addressing widespread informalities in timber production, based on the presumed links between formalisation, the maintenance of forest cover and local welfare. This trend is typified by the EU Forest Law Enforcement, Governance and Trade (FLEGT) initiative and associated Voluntary Partnership Agreements (VPA) aimed at eradicating the trade of illegal wood between partner countries and the EU. Yet there is concern that such initiatives might have detrimental impacts on the largely informal rights of local resource users. In order to inform the formalisation agenda, more detailed analysis of the operation of local rights, and how they might be affected by particular schemes is required.This paper focuses on Ghana as a country with a largely informal wood sector that has signed a VPA with the EU for the express purpose of rapid formalisation. Our analysis is guided by a framework for assessing which types of rights might be transformed by particular approaches to formalisation and the subsequent effect this might have on forests and people in particular local contexts. We then apply this framework to an in-depth local case study of on-farm timber governance within a cocoa-forest landscape in Ghana's Central Region to examine how the operation of formal and informal and substantive and procedural rights shape who controls, and benefits from, on-farm timber production. We then analyse the content of the VPA in light of these local realities and assess its potential impacts.Our findings highlight how the substantive rights the state grants to companies are presumed to be balanced with the granting of procedural rights to farmers via the mechanisms of right of refusal to harvest on-farm timber, compensation for damage to cocoa crops and the negotiation of community-level Social Responsibility Agreements with private companies. Yet a comparison of these formal rights with farmers' existing informal rights reveals that farmers' control and access to benefits from trees on their farms are notably higher in the 'illegal' chainsaw dominated informal sector than in the 'legal' state-based system. Farmers choose to maintain trees on farms both to shade cocoa and in anticipation of benefits from their informal sale. The VPA, however, aims to eradicate all informal on-farm timber production and thus threatens existing local rights and benefit capture while diminishing incentives to maintain trees on farm. Rather than further criminalising local systems of timber governance, the maintenance of tree cover and local benefit-sharing would be better served by 1) phasing out timber concessions on farmland, 2) abandoning the distinction between planted and native trees on farms and, 3) understanding, recognizing and respecting the existing informal rights of farmers, traditional authorities and chainsaw loggers to negotiate among themselves patterns of access and control of on-farm trees and timber. In general, the case study challenges the assertion that formalisation is requisite for sustainable forest management and mandates a more nuanced and contextually informed assessment of the assumed costs and benefits associated with particular forms of legal and policy reform.
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| 9. |
- Hirons, M., et al.
(författare)
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Understanding climate resilience in Ghanaian cocoa communities – Advancing a biocultural perspective
- 2018
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Ingår i: Journal of Rural Studies. - : Elsevier BV. - 0743-0167. ; 63, s. 120-129
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Tidskriftsartikel (refereegranskat)abstract
- This paper aims to contribute to the ongoing conceptual development and practical pursuit of resilience, the ability to absorb and respond to shocks, in an agricultural and climate change context. It builds on work that aims to dissolve the nature-society dualism and naturalisation of power relations inherent in systems thinking by developing and extending a framework originally conceived to integrate research on biological and cultural diversity. The resultant ‘biocultural’ framework examines livelihood practices, institutions, knowledge and beliefs and is applied to a case study of cocoa communities in Ghana's Central Region. Drawing on data collected over three years spanning an El Niño Southern Oscillation (ENSO) related drought event, the analysis demonstrates the utility of an expanded conception of resilience that links livelihood practices, which define the impact and response to droughts, with the constituent knowledge, institutions and beliefs that shape those practices. The study focuses on two key factors that underpin cocoa farmers' resilience to climate shocks: access to wetlands and access to credit. We argue that particular characteristics of livelihood practices, knowledge, belief and institutions, and their interactions, can be both resilience enhancing and undermining, when viewed at different spatial, temporal and social scales. Although such contradictions present challenges to policy-makers engaging with climate resilience, the analysis provides a clearer diagnoses of key challenges to the resilience of agricultural systems and insights into where policy interventions might be most effective.
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| 10. |
- Hirons, M., et al.
(författare)
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Understanding Poverty in Cash-crop Agro-forestry Systems : Evidence from Ghana and Ethiopia
- 2018
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Ingår i: Ecological Economics. - : Elsevier BV. - 0921-8009. ; 154, s. 31-41
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines the linkages between cash-crop income and other dimensions of poverty to interrogate assumptions regarding the relationship between agricultural income and poverty alleviation. The analysis treats poverty as a multi-dimensional and socially disaggregated phenomenon. The paper employs a mixed methods approach to case studies of Ghana and Ethiopia to explore two critical issues. First, how income from cash crops is linked with other dimensions of poverty. Second, how income and land are socially disaggregated. The paper then draws on qualitative data to critically reflect on how poverty is understood within studied communities. The results show that some, but not all, indicators of poverty vary across income quartiles and that significant differences exist across social groups. The analysis suggests that although cash crops are essential, focusing on increasing income from cash crops will not necessarily have a predictable or progressive impact on wellbeing. Furthermore, the analysis highlights how contextual factors, such as the provision of communal services, the nature of land holdings and the quality of local governance mediate the potential poverty alleviating outcomes of income increases. Future development of sustainable intensification strategies should focus on the prevalence of trade-offs and the fundamental social relations underpinning poverty dynamics.
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