Research priorities for managing the impacts and dependencies of business upon food, energy, water and the environment

Delivering access to sufficient food, energy and water resources to ensure human wellbeing is a major concern for governments worldwide. However, it is crucial to account for the ‘nexus’ of interactions between these natural resources and the consequent implications for human wellbeing. The private sector has a critical role in driving positive change towards more sustainable nexus management and could reap considerable benefits from collaboration with researchers to devise solutions to some of the foremost sustainability challenges of today. Yet opportunities are missed because the private sector is rarely involved in the formulation of deliverable research priorities. We convened senior research scientists and influential business leaders to collaboratively identify the top forty questions that, if answered, would best help companies understand and manage their food-energy-water-environment nexus dependencies and impacts. Codification of the top order nexus themes highlighted research priorities around development of pragmatic yet credible tools that allow businesses to incorporate nexus interactions into their decision-making; demonstration of the business case for more sustainable nexus management; identification of the most effective levers for behaviour change; and understanding incentives or circumstances that allow individuals and businesses to take a leadership stance. Greater investment in the complex but productive relations between the private sector and research community will create deeper and more meaningful collaboration and cooperation.This work was supportedby the Economic and Social Research Council [Grant Number ES/L01632X/1] and is part of the Nexus Network Initiative. WJS is funded by Arcadia

Treatment outcomes in HIV-infected adolescents attending a community-based antiretroviral therapy clinic in South Africa

<p>Abstract</p> <p>Background</p> <p>Very few data are available on treatment outcomes of adolescents living with HIV infection (whether perinatally acquired or sexually acquired) in sub-Saharan Africa. The present study therefore compared the treatment outcomes in adolescents with those of young adults at a public sector community-based ART programme in Cape Town, South Africa.</p> <p>Methods</p> <p>Treatment outcomes of adolescents (9-19 years) were compared with those of young adults (20-28 years), enrolled in a prospective cohort between September 2002 and June 2009. Kaplan-Meier estimates and Cox proportional hazard models were used to assess outcomes and determine associations with age, while adjusting for potential confounders. The treatment outcomes were mortality, loss to follow-up (LTFU), immunological response, virological suppression and virological failure.</p> <p>Results</p> <p>883 patients, including 65 adolescents (47 perinatally infected and 17 sexually infected) and 818 young adults, received ART. There was no difference in median baseline CD4 cell count between adolescents and young adults (133.5 vs 116 cells/μL; <it>p </it>= 0.31). Overall mortality rates in adolescents and young adults were 1.2 (0.3-4.8) and 3.1 (2.4-3.9) deaths per 100 person-years, respectively. Adolescents had lower rates of virological suppression (< 400 copies/mL) at 48 weeks (27.3% vs 63.1%; <it>p </it>< 0.001). Despite this, however, the median change in CD4 count from baseline at 48 weeks of ART was significantly greater for adolescents than young adults (373 vs 187 cells/μL; <it>p </it>= 0.0001). Treatment failure rates were 8.2 (4.6-14.4) and 5.0 (4.1-6.1) per 100 person-years in the two groups. In multivariate analyses, there was no significant difference in LTFU and mortality between age groups but increased risk in virological failure [AHR 2.06 (95% CI 1.11-3.81; <it>p </it>= 0.002)] in adolescents.</p> <p>Conclusions</p> <p>Despite lower virological suppression rates and higher rates of virological failure, immunological responses were nevertheless greater in adolescents than young adults whereas rates of mortality and LTFU were similar. Further studies to determine the reasons for poorer virological outcomes are needed.</p

Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development

The growth factor family of neurotrophins has major roles both inside and outside the nervous system. Here, we report a detailed histological analysis of key phenotypes generated by the ablation of the Kinase D interacting substrate of 220 kDa/Ankyrin repeat-rich membrane spanning (Kidins220/ARMS) protein, a membrane-anchored scaffold for the neurotrophin receptors Trk and p75NTR. Kidins220 is important for heart development, as shown by the severe defects in the outflow tract and ventricle wall formation displayed by the Kidins220 mutant mice. Kidins220 is also important for peripheral nervous system development, as the loss of Kidins220 in vivo caused extensive apoptosis of DRGs and other sensory ganglia. Moreover, the neuronal-specific deletion of this protein leads to early postnatal death, showing that Kidins220 also has a critical function in the postnatal brain

Sicily statement on classification and development of evidence-based practice learning assessment tools

<p>Abstract</p> <p>Background</p> <p>Teaching the steps of evidence-based practice (EBP) has become standard curriculum for health professions at both student and professional levels. Determining the best methods for evaluating EBP learning is hampered by a dearth of valid and practical assessment tools and by the absence of guidelines for classifying the purpose of those that exist. Conceived and developed by delegates of the Fifth International Conference of Evidence-Based Health Care Teachers and Developers, the aim of this statement is to provide guidance for purposeful classification and development of tools to assess EBP learning.</p> <p>Discussion</p> <p>This paper identifies key principles for designing EBP learning assessment tools, recommends a common taxonomy for new and existing tools, and presents the Classification Rubric for EBP Assessment Tools in Education (CREATE) framework for classifying such tools. Recommendations are provided for developers of EBP learning assessments and priorities are suggested for the types of assessments that are needed. Examples place existing EBP assessments into the CREATE framework to demonstrate how a common taxonomy might facilitate purposeful development and use of EBP learning assessment tools.</p> <p>Summary</p> <p><it>The widespread adoption of EBP into professional education requires valid and reliable measures of learning. Limited tools exist with established psychometrics. This international consensus statement strives to provide direction for developers of new EBP learning assessment tools and a framework for classifying the purposes of such tools</it>.</p

Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge

<p>Abstract</p> <p>Background</p> <p>There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown.</p> <p>Methods</p> <p>To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation.</p> <p>Results</p> <p>Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors.</p> <p>Conclusion</p> <p>Our results demonstrate that predatory stress, an ethologically relevant stressor, can elicit changes in neuroinflammation and behavior. The predatory stress model may be useful in elucidating mechanisms by which psychological stress modulates diseases with an inflammatory component.</p

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models

Cracking the BAFF code.

The tumour necrosis factor (TNF) family members B cell activating factor (BAFF) and APRIL (a proliferation-inducing ligand) are crucial survival factors for peripheral B cells. An excess of BAFF leads to the development of autoimmune disorders in animal models, and high levels of BAFF have been detected in the serum of patients with various autoimmune conditions. In this Review, we consider the possibility that in mice autoimmunity induced by BAFF is linked to T cell-independent B cell activation rather than to a severe breakdown of B cell tolerance. We also outline the mechanisms of BAFF signalling, the impact of ligand oligomerization on receptor activation and the progress of BAFF-depleting agents in the clinical setting

Plant growth-promoting actinobacteria: a new strategy for enhancing sustainable production and protection of grain legumes

Grain legumes are a cost-effective alternative for the animal protein in improving the diets of the poor in South-East Asia and Africa. Legumes, through symbiotic nitrogen fixation, meet a major part of their own N demand and partially benefit the following crops of the system by enriching soil. In realization of this sustainability advantage and to promote pulse production, United Nations had declared 2016 as the “International Year of pulses”. Grain legumes are frequently subjected to both abiotic and biotic stresses resulting in severe yield losses. Global yields of legumes have been stagnant for the past five decades in spite of adopting various conventional and molecular breeding approaches. Furthermore, the increasing costs and negative effects of pesticides and fertilizers for crop production necessitate the use of biological options of crop production and protection. The use of plant growth-promoting (PGP) bacteria for improving soil and plant health has become one of the attractive strategies for developing sustainable agricultural systems due to their eco-friendliness, low production cost and minimizing consumption of non-renewable resources. This review emphasizes on how the PGP actinobacteria and their metabolites can be used effectively in enhancing the yield and controlling the pests and pathogens of grain legumes