A Realist Review of How Community-Based Drug Checking Services Could Be Designed and Implemented to Promote Engagement of People Who Use Drugs

With rising numbers of drug-related deaths in the UK and globally, exploration of interventions that seek to reduce drug-related harm is essential. Drug checking services (DCS) allow people to submit drug samples for chemical analysis and receive feedback about the sample, as well as harm reduction advice. The use of DCS is often linked to festival and/or nightlife settings and to so-called ‘recreational’ drug use, but research has also shown the potential of community-based DCS as an intervention serving more varied demographics of people who use drugs, including more marginalised individuals and those experiencing drug dependence. Whilst there is a growing evidence base on the effectiveness of drug checking as a harm reduction intervention, there is still limited evidence of the underlying mechanisms and processes within DCS which may aid implementation and subsequent engagement of people who use drugs. This presents a challenge to understanding why engagement differs across types of DCS, and how best to develop and deliver services across different contexts and for different populations. To explore the contexts and mechanisms which impact engagement in community-based DCS, a realist review was undertaken to synthesise the international evidence for the delivery and implementation of DCS. There were 133 sources included in the review. From these sources the underlying contexts, mechanisms, and outcomes relating to DCS implementation and engagement were developed and refined into seven programme theories. The findings of this review are theoretically novel and hold practical relevance for the design of DCS, with implications for optimisation, tailoring, and implementing services to reach individuals in different settings

A realist review of how community-based drug checking services could be designed and implemented to promote engagement of people who use drugs

With rising numbers of drug-related deaths in the UK and globally, exploration of interventions that seek to reduce drug-related harm is essential. Drug checking services (DCS) allow people to submit drug samples for chemical analysis and receive feedback about the sample, as well as harm reduction advice. The use of DCS is often linked to festival and/or nightlife settings and to so-called ‘recreational’ drug use, but research has also shown the potential of community-based DCS as an intervention serving more varied demographics of people who use drugs, including more marginalised individuals and those experiencing drug dependence. Whilst there is a growing evidence base on the effectiveness of drug checking as a harm reduction intervention, there is still limited evidence of the underlying mechanisms and processes within DCS which may aid implementation and subsequent engagement of people who use drugs. This presents a challenge to understanding why engagement differs across types of DCS, and how best to develop and deliver services across different contexts and for different populations. To explore the contexts and mechanisms which impact engagement in community-based DCS, a realist review was undertaken to synthesise the international evidence for the delivery and implementation of DCS. There were 133 sources included in the review. From these sources the underlying contexts, mechanisms, and outcomes relating to DCS implementation and engagement were developed and refined into seven programme theories. The findings of this review are theoretically novel and hold practical relevance for the design of DCS, with implications for optimisation, tailoring, and implementing services to reach individuals in different settings

Assessing progress towards meeting major international objectives related to nature and nature's contributions to people

In recognition of the importance of nature, its contributions to people and role in underpinning sustainable development, governments adopted a Strategic Plan on Biodiversity 2011-2020 through the Convention on Biological Diversity (CBD) containing 20 "Aichi Biodiversity Targets" and integrated many of these into the Sustainable Development Goals (SDGs) adopted through the United Nations in 2015. Additional multilateral environmental agreements (MEAs) target particular aspects of nature (e.g., Ramsar Convention on Wetlands; Convention on Migratory Species), drivers of biodiversity loss (e.g., Convention on International Trade in Endangered Species of Wild Fauna and Flora), or responses (e.g., World Heritage Convention). These various MEAs provide complementary fora in which governments strive to coordinate efforts to reduce the loss and degradation of nature, and to promote sustainable development. In this chapter, we assess, through a systematic review process and quantitative analysis of indicators, progress towards the 20 Aichi Targets under the Strategic Plan (and each of the 54 elements or components of these targets), targets under the SDGs that are relevant to nature and nature's contributions to people (NCP), and the goals and targets of six other MEAs. We consider the relationships between the SDGs, nature and the contributions of Indigenous Peoples and Local Communities (IPLCs) to achieving the various targets and goals, the impact of progress or lack of it on IPLCs, the reasons for variation in progress, implications for a new Strategic Plan for Biodiversity beyond 2020, and key knowledge gaps.For the 44 SDG targets assessed, including targets for poverty, hunger, health, water, cities, climate, oceans and land (Goals 1, 2, 3, 6, 11, 13, 14, 15), findings suggest that current negative trends in nature will substantially undermine progress to 22 SDG targets and result in insufficient progress to meet 13 additional targets (i.e. 80 per cent (35 out of 44) of the assessed targets) {3.3.2.1; 3.3.2.2}(established but incomplete). Across terrestrial, aquatic and marine ecosystems, current negative trends in nature and its contributions will hamper SDG progress, with especially poor progress expected towards targets on water security, water quality, ocean pollution and acidification. Trends in nature's contributions relevant to extreme event vulnerability, resource access, small-scale food production, and urban and agricultural sustainability are negative and insufficient for achieving relevant targets under SDGs 1, 2, 3, and 11. This has negative consequences for both the rural and urban poor who are also directly reliant on declining resources for consumption and income generation {3.3.2.2}. For a further 9 targets evaluated in SDGs 1, 3 and 11 a lack of knowledge on how nature contributes to targets (4 targets) or gaps in data with which to assess trends in nature (5 targets) prevented their assessment.Fil: Butchart, Stuart. London Metropolitan University; Reino UnidoFil: Miloslavich, Patricia. University of Western Australia; AustraliaFil: Reyers, Belinda. No especifíca;Fil: Galetto, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Subramanian, Suneetha M.. No especifíca;Fil: Adams, Cristina. No especifíca;Fil: Palomo, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: McElwee, Pamela. No especifíca;Fil: Meretsky, Vicky J.. No especifíca;Fil: Morsello, Carla. No especifíca;Fil: Nel, Jeanne. No especifíca;Fil: Lynn Newberry, Teresa. No especifíca;Fil: Pacheco, Diego. No especifíca;Fil: Pyhala, Aili. No especifíca;Fil: Rossi Heras, Sergio. No especifíca;Fil: Roy, Joyashree. No especifíca;Fil: Ruiz-Mallén, Isabel. No especifíca;Fil: Salpeteur, Matthieu. No especifíca;Fil: Santos-Martin, Fernando. No especifíca;Fil: Saylor. Kirk. No especifíca;Fil: Schaffartzik, Anke. No especifíca;Fil: Sitas, Nadia. No especifíca;Fil: Speranza, Ifejika. No especifíca;Fil: Suich, Helen. No especifíca;Fil: Tittensor, Derek. No especifíca;Fil: Carignano, Patricia. No especifíca;Fil: Tsioumani, Elsa. No especifíca;Fil: Whitmee, Sarah. No especifíca;Fil: Wilson, Sarah. No especifíca;Fil: Wyndham, Felice. No especifíca;Fil: Zorondo-Rodriguez, Francisco. No especifíca

Quantification of appetite-regulating hormones in children with hypothalamic and common obesity

Background. Current understanding of the appetite-regulating neuroendocrine circuitry remains incomplete, and efficacious treatments for both common and hypothalamic obesity (HyOb) are lacking. Concurrently, the expanded role of oxytocin (OXT) in energy homeostasis and human behaviour is beginning to be understood. Objectives. To optimise and translate an OXT enzyme immunoassay (EIA) to elucidate whether there were any unique differences in the plasma endocrine milieu in patients with HyOb. Methods. Optimisation work was carried out using EIAs with polyclonal and monoclonal secondary antibodies. Obese (BMI>+2 SDS) and lean (BMI≤+2 SDS) children with (HyOb and HyLean) and without (Ob and Lean) hypothalamic disorders (septo-optic dysplasia or suprasellar tumours) were phenotyped using the Dykens’ Hyperphagia Questionnaire Score (DHQS). Plasma concentrations of leptin, insulin, OXT, BDNF, αMSH, acylated ghrelin, AgRP and copeptin were measured. Results. Solid phase extraction demonstrated markedly variable OXT recovery, and potentially increased rather than decreased interference. A polyclonal secondary antibody-containing EIA showed significant cross-reactivity with several peptides in human plasma compared to a monoclonal secondary antibody-containing EIA. Of the 122 children recruited (50 HyOb, 29 HyLean, 24 Ob, 19 Lean, mean age 11.3±3.9 years) there were no differences in DHQS or hormone concentrations between HyOb and Ob groups. Obesity was associated with compensatorily increased leptin and insulin, and decreased ghrelin and AgRP concentrations. More rapidly increasing BMI was independently associated with a younger age and lower plasma αMSH concentrations. OXT concentrations did not show any correlation with BMI or DHQS. Conclusion. The use of plasma extraction processes and EIAs in the literature needs re-examination. The plasma endocrine milieu in HyOb vs. common obesity does not differ, with a compensatory increase in anorexigens and decrease in orexigens. Lower plasma αMSH was associated with more rapid weight gain, suggesting that MC4R agonists may be a therapeutic option in all forms of obesity

Effects of azadirachtin on insect and mammalian cultured cells

The aim of this project was to try to find the mode of action of azadirachtin in cultured cells, and to compare its cytotoxicity with some well-known phytochemical pesticides. The results presented here showed that azadirachtin was toxic to the cultured insect cells used (Sf9 and C6/36, derived respectively from Spodoptera frugiperda and Aedes albopictus) even in very low concentrations with an EC50 for the Spodoptera cells estimated at 5x10-9 M, but that the mammalian fibroblast cell line L929 was little affected except at concentrations greater than 10-4M. The other major neem terpenoids, nimbin and salannin, showed low toxicity towards the cultured cells. The neurotoxic pyrethrum showed little effect against the cultures, except for some slight stimulatory effect on growth at 10-8 M. Rotenone, known to inhibit the electron transport chain, effectively inhibited the growth of both insect and mammalian cells. Nicotine, another neurotoxic phytochemical, had little effect on the growth of the cultured cells. It was concluded that while cell growth assessment is not appropriate for all phytochemical pesticides, it is useful for those, such as azadirachtin and rotenone, whose effect is on the essential mechanisms of insect cells in general. Rotenone was used as a positive control to investigate if azadirachtin had its effect on respiration of the cells. Only at the highest feasible concentration of azadirachtin, was there a slight but significant (15%) reduction of respiration which was the same in both insect and mammalian cells. As expected, rotenone inhibited both insect and mammalian cells even at concentrations as low as 10-11 M. When the effects of azadirachtin on the cell cycle were examined by means of cell cytometry, it was shown that the compound arrested the cell-cycle in G2/M phase, and that the effect was related to the concentration. Microscopy confirmed that there was a three-fold increase in the mitotic index after 2 hours of exposure of 2x10-6 M azadirachtin. The similarity of the of the nuclear profiles and cell-cycle distribution to Sf9 cells treated with colchicine, a well-known antimitotic phytochemical, suggested there was a similarity of action between the two compounds