Investigating the evolution of apoptosis in malaria parasites: the importance of ecology

Apoptosis is a precisely regulated process of cell death which occurs widely in multicellular organisms and is essential for normal development and immune defences. In recent years, interest has grown in the occurrence of apoptosis in unicellular organisms. In particular, as apoptosis has been reported in a wide range of species, including protozoan malaria parasites and trypanosomes, it may provide a novel target for intervention. However, it is important to understand when and why parasites employ an apoptosis strategy before the likely long-and short-term success of such an intervention can be evaluated. The occurrence of apoptosis in unicellular parasites provides a challenge for evolutionary theory to explain as organisms are expected to have evolved to maximise their own proliferation, not death. One possible explanation is that protozoan parasites undergo apoptosis in order to gain a group benefit from controlling their density as this prevents premature vector mortality. However, experimental manipulations to examine the ultimate causes behind apoptosis in parasites are lacking. In this review, we focus on malaria parasites to outline how an evolutionary framework can help make predictions about the ecological circumstances under which apoptosis could evolve. We then highlight the ecological considerations that should be taken into account when designing evolutionary experiments involving markers of cell death, and we call for collaboration between researchers in different fields to identify and develop appropriate markers in reference to parasite ecology and to resolve debates on terminology.Host-parasite interactio

Inefficiency persistence and heterogeneity in Colombian electricity distribution utilities

The electricity reform in Colombia has exhibited gains in terms of reliability but its effects on firms efficiency and service quality have not been clear. Previous studies evaluating the performance of distribution companies after the reform have not found evidence of improvements, although large differences in efficiency have been found among firms. This suggests high inefficiency persistence and heterogeneity in the Colombian distribution sector. In this paper, we propose an extension of dynamic stochastic frontier models that accounts for unobserved heterogeneity in the inefficiency persistence and in the technology. The model incorporates total expenses, service quality and energy losses in an efficiency analysis of Colombian distributors over fifteen years after the reform. We identify the presence of high inefficiency persistence in the sector, and important differences between firms. In particular, rural companies and firms with small customers present low persistence and evidence the largest gains in efficiency during the period. However, increases in efficiency are only manifested during the last five years when the main improvements in service quality and energy losses are presented. Overall, inefficiency persistence, customer density and consumption density are found to be important criteria to be considered for regulatory purposes

The Meaning of Death: Evolution and Ecology of Apoptosis in Protozoan Parasites

The discovery that an apoptosis-like, programmed cell death (PCD) occurs in a broad range of protozoan parasites offers novel therapeutic tools to treat some of the most serious infectious diseases of humans, companion animals, wildlife, and livestock. Whilst apoptosis is an essential part of normal development, maintenance, and defence in multicellular organisms, its occurrence in unicellular parasites appears counter-intuitive and has proved highly controversial: according to the Darwinian notion of “survival of the fittest”, parasites are expected to evolve strategies to maximise their proliferation, not death. The prevailing, and untested, opinion in the literature is that parasites employ apoptosis to “altruistically” self-regulate the intensity of infection in the host/vector. However, evolutionary theory tells us that at most, this can only be part of the explanation, and other non-mutually exclusive hypotheses must also be tested. Here, we explain the evolutionary concepts that can explain apoptosis in unicellular parasites, highlight the key questions, and outline the approaches required to resolve the controversy over whether parasites “commit suicide”. We highlight the need for integration of proximate and functional approaches into an evolutionary framework to understand apoptosis in unicellular parasites. Understanding how, when, and why parasites employ apoptosis is central to targeting this process with interventions that are sustainable in the face of parasite evolution

The Problem of Auto-Correlation in Parasitology

Explaining the contribution of host and pathogen factors in driving infection dynamics is a major ambition in parasitology. There is increasing recognition that analyses based on single summary measures of an infection (e.g., peak parasitaemia) do not adequately capture infection dynamics and so, the appropriate use of statistical techniques to analyse dynamics is necessary to understand infections and, ultimately, control parasites. However, the complexities of within-host environments mean that tracking and analysing pathogen dynamics within infections and among hosts poses considerable statistical challenges. Simple statistical models make assumptions that will rarely be satisfied in data collected on host and parasite parameters. In particular, model residuals (unexplained variance in the data) should not be correlated in time or space. Here we demonstrate how failure to account for such correlations can result in incorrect biological inference from statistical analysis. We then show how mixed effects models can be used as a powerful tool to analyse such repeated measures data in the hope that this will encourage better statistical practices in parasitology

Valtion aluehallintovirastot ja niiden ylijohtajat: Pohjoiseurooppalainen analogia Ranskan prefeikteille

This chapter examines the closest Finnish analogy to the French function of the prefect. In Finland, since 2010, this function has been vested in the institution of the State Regional Administrative Agency (SRAA, aluehallintovirasto, ‘AVI’). There are six SRAAs, each headed by a Chief Director (ylijohtaja) nominated by the government. The study had four main findings. First, despite ambiguity in institutional terminology, classifications, boundaries and identities concerning the SRAA, one can discern few true functional or structural deficiencies. Second, the SRAA is a hybrid between an institution of its own and a territorial representative of either government ministries or government agencies, to which is related the fact that each SRAA has both responsibilities concerning its territory and nationwide responsibilities. Third, tensions between performance and institutional legitimation prevail in the institution of the SRAA, but again without serious deficiencies. Fourth, the 2010 substitution of the SRAA for the former Province comprised a radical institutional change. The 2015–2019 Finnish government intended to abolish the SRAAs, but the subsequent government abandoned that reform, and ultimately by mid-2020 it became clear that the institution of the SRAA was here to stay after all.Peer reviewe

Size matters: the value of small populations for wintering waterbirds

Protecting systematically selected areas of land is a major step towards biodiversity conservation worldwide. Indeed, the identification and designation of protected areas more often than not forms a core component of both national and international conservation policies. In this paper we provide an overview of those Special Protection Areas and Ramsar Sites that have been classified in Great Britain as of 1998/99 for a selection of wintering waterbird species, using bird count data from the Wetland Bird Survey. The performance of this network of sites is remarkable, particularly in comparison with published analyses of networks elsewhere in the world. Nevertheless, the current site-based approach, whilst having the great benefit of simplicity, is deliberately biased towards aggregating species at the expense of the more dispersed distribution species. To ensure that the network continues successfully to protect nationally and internationally important waterbird populations, efforts now need to concentrate on the derivation of species-specific representation targets and, in particular, the ways in which these can be incorporated into the site selection process. Although these analyses concern the performance of protected areas for waterbirds in Great Britain, the results have wide-ranging importance for conservation planning in general and the design of protected area networks

Equine lamellar energy metabolism studied using tissue microdialysis

Failure of lamellar energy metabolism may contribute to the pathophysiology of equine laminitis. Tissue microdialysis has the potential to dynamically monitor lamellar energy balance over time. The objectives of this study were to develop a minimally invasive lamellar microdialysis technique and use it to measure normal lamellar energy metabolite concentrations over 24h. Microdialysis probes were placed (through the white line) into either the lamellar dermis (LAM) (n=6) or the sublamellar dermis (SUBLAM) (n=6) and perfused continuously over a 24h study period. Probes were placed in the skin dermis (SKIN) for simultaneous comparison to LAM (n=6). Samples were collected every 2h and analysed for glucose, lactate, pyruvate, urea and glycerol concentrations. LAM was further compared with SUBLAM by simultaneous placement and sampling in four feet from two horses over 4h. Horses were monitored for lameness, and either clinically evaluated for 1month after probe removal (n=4) or subjected to histological evaluation of the probe site (n=10).There were no deleterious clinical effects of probe placement and the histological response was mild. Sample fluid recovery and metabolite concentrations were stable for 24h. Glucose was lower (and lactate:glucose ratio higher) in LAM compared with SUBLAM and SKIN (

Mainstreaming the Water-Energy-Food Nexus through nationally determined contributions (NDCs): the case of Brazil

The Water-Energy-Food Nexus approach to the governance of natural resources seeks to identify and address the synergies and trade-offs amongst traditionally separated sectors, to capture significant feedbacks that have so far remained insufficiently understood and regulated. One key specificity of the Nexus approach is the need for intersectoral, cross-scale and stakeholder integration, which is particularly challenging due to the lack of policy coordination prevailing in many countries. Yet, some emerging integrated policy processes, such as those aimed at implementing nationally determined contributions (NDCs) under the 2015 Paris Agreement, may offer a sufficient level of integration to mainstream the Nexus approach. This article focuses on the potential of such NDC processes in Brazil. NDC processes in China, the European Union, India and Mexico are used as indicators associated with higher or lower degrees of integration for a more specific analysis of the case of Brazil. The article concludes that the barriers to sectoral integration raised by the dominant position of the agricultural sector in Brazil as regards, among other things, environmental legislation, are unlikely to be overcome by internal action. This represents a threat to achieving the target of zero deforestation in Brazil, considering the cropland-livestock forestry feedbacks involved in the growing demand for agricultural commodities from China. NDCs already provide space for international cooperation, which could be further developed to include measures for linking demand for agricultural commodities from the EU and China, and massive land-use change and deforestation in Brazil

The medium-term sustainability of organisational innovations in the national health service

Background: There is a growing recognition of the importance of introducing new ways of working into the UK's National Health Service (NHS) and other health systems, in order to ensure that patient care is provided as effectively and efficiently as possible. Researchers have examined the challenges of introducing new ways of working-'organisational innovations'-into complex organisations such as the NHS, and this has given rise to a much better understanding of how this takes place-and why seemingly good ideas do not always result in changes in practice. However, there has been less research on the medium-and longer-term outcomes for organisational innovations and on the question of how new ways of working, introduced by frontline clinicians and managers, are sustained and become established in day-to-day practice. Clearly, this question of sustainability is crucial if the gains in patient care that derive from organisational innovations are to be maintained, rather than lost to what the NHS Institute has called the 'improvement-evaporation effect'. Methods: The study will involve research in four case-study sites around England, each of which was successful in sustaining its new model of service provision beyond an initial period of pilot funding for new genetics services provided by the Department of Health. Building on findings relating to the introduction and sustainability of these services already gained from an earlier study, the research will use qualitative methods-in-depth interviews, observation of key meetings, and analysis of relevant documents-to understand the longer-term challenges involved in each case and how these were surmounted. The research will provide lessons for those seeking to sustain their own organisational innovations in wide-ranging clinical areas and for those designing the systems and organisations that make up the NHS, to make them more receptive contexts for the sustainment of innovation. Discussion: Through comparison and contrast across four sites, each involving different organisational innovations, different forms of leadership, and different organisational contexts to contend with, the findings of the study will have wide relevance. The research will produce outputs that are useful for managers and clinicians responsible for organisational innovation, policy makers and senior managers, and academics