Bioactive molecules isolated from plants are promising sources for the development of new therapies against leishmaniasis. We investigated the leishmanicidal activity of cariphenone A (1), isouliginosin B (2) and uliginosin B (3) isolated from Hypericum species. Promastigotes and amastigotes of Leishmania amazonensis were incubated with compounds 1-3 at concentrations 1-100 µm for 48 h. The anti-promastigote effect of compounds was also tested in combinations. The cytotoxicity against macrophages and human erythrocytes were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method and hemolysis assay, respectively. The compounds 1-3 showed high leishmanicidal activity against promastigotes, IC50 values of 10.5, 17.5 and 11.3 µm, respectively. Synergistic interactions were found to the associations of compounds 1 and 2 [Σ fractional inhibitory concentration (FIC) = 0.41], and 2 and 3 (ΣFIC = 0.28) on promastigotes. All Hypericum compounds induced mitochondrial hyperpolarization and reactive oxygen species production in promastigotes. The compounds showed low cytotoxicity toward mammalian cells, high selectivity index and killed intracellular amastigotes probably mediated by oxidative stress. These results indicate that these compounds are promising candidates for the development of drugs against leishmaniasis.
Objective: Millions of children suffer from severe acute malnutrition (SAM) in low- and middle-income countries. Much is known about the effectiveness of community treatment programmes (CMAM) but little is known about post-discharge outcomes after successful treatment. The present study aimed to evaluate post-discharge outcomes of children cured of SAM. Design: Prospective, observational cohort study. Children with SAM who were discharged as cured were followed monthly for 6 months or until they experienced relapse to SAM. 'Cure' was defined as a child achieving a mid-upper arm circumference (MUAC) of >= 115 mm with >= 15 % weight gain after loss of oedema. Relapse was defined as a child with MUAC < 115 mm and/or oedema at any monthly visit. Setting: Save the Children CMAM programme in Swabi, Pakistan, from January 2012 to December 2014. Subjects: Children aged 6-59 months (n 117) discharged as cured from the CMAM programme were eligible for the study and followed for 6 months. Results: One hundred children (92.6%) remained free of SAM, eight (7.4%) relapsed to SAM, nine (8.3%) were lost to follow-up and none died. Most relapses occurred within 3 months of discharge (mean time to relapse 73.4 (SD 36.2) d). At enrolment, 90% had moderate acute malnutrition (MAM) and 10% were not malnourished. By the end of 6 months, 35% persisted with MAM and the remaining were not malnourished. Conclusions: In rural Pakistan, fewer than 10% of children cured of SAM relapsed. The first 3 months is the most vulnerable time.
Under the Conservative-Liberal Coalition Government and the Conservative Government that took office in 2015, policy measures were introduced to develop a Social Impact Investment Market that harnesses private finance to invest in services to achieve social and financial outcomes. This nascent market is of growing interest amongst social scientists (Bryan and Rafferty, 2014; Whitfield, 2015; McHugh et al., 2013; Dowling, 2017; Edmiston and Nicholls, 2017), but little attention has been given to interrogating related UK Government discourse. The originality of this paper is its contribution to addressing this 'discourse gap'; enhancing our understanding of the development and representation of impact investment in the UK. Using Hyatt's (2013a) Critical Policy Discourse Analysis Framework, a rigorous critical examination of UK Coalition and Conservative Government impact investment discourse between 2011 and 2016 is undertaken. The significance of this work lies in its contextualisation and deconstruction of UK Government texts to identify and unpack how distinct rationales, justifications and legitimations draw on and (re)produce a Broken Britain-Big Society narrative (Wiggan, 2011; Dowling and Harvie, 2014; Smith and Jones, 2015) to 'policy booster' financialised reconfiguration of the welfare state as the route to a better society.
AbstractThis article argues that it is important for the International Court of Justice to be given an opportunity, for instance through a request for an Advisory Opinion, to explain what exactly it meant when it suggested that the ordinarily applicable international law on immunities need not be an obstacle “before certain international criminal courts, where they have jurisdiction”. Two international criminal courts have built a structure of case law on this one obiter comment, which it seems unable to support.
AbstractThis article seeks to defend the law of unjust enrichment against the recent influential attacks of Robert Stevens (“The Unjust Enrichment Disaster” (2018) 134 LQR 574) and Lionel Smith (“Restitution: A New Start?” in Devonshire and Havelock, The Impact of Equity and Restitution in Commerce (2018), ch. 5). A central argument here put forward is that there is a law of unjust enrichment, embodying a cause of action in unjust enrichment, which unites what Stevens and Smith see as disparate categories. A linked but separate argument is that, within the central area of unjust enrichment, Stevens is incorrect to regard the defendant's acceptance of performance as being necessary to trigger restitution albeit that acceptance may be relevant in establishing that the defendant has been enriched. A further, and more specific, argument is that, with great respect, the overruling, as a matter of principle, of Sempra Metals Ltd. v IRC  UKHL 34,  1 A.C. 561, by the Supreme Court in Prudential Assurance Ltd. v HMRC  UKSC 39,  3 WLR 652, seems unfortunate and appears to have been influenced by Stevens's excessively narrow approach to the meaning of “at the expense of”.
Abstract Vicarious liability was, and it remains, curiously unsatisfactory. After a period of stability from the Middle Ages into the early modern period in the late seventeenth into the early eighteenth century, the existing law of vicarious liability began to be challenged. The mid-nineteenth century saw another reappraisal coinciding with the rise of notions of fault. The period that follows, from the late nineteenth century until after the Second World War period has not attracted much comment. One key debate in this period and earlier which provides a useful lens to examine the doctrine was whether vicarious liability should be properly characterised as a master's or servant's tort theory. The history of the doctrine during this period goes some way to explaining why the modern law remains incoherent.
AbstractThe author makes two claims in this paper. First, there appears to be an increase in indications of inconsistency (“IoIs”) across the common law world. Second, this increase is a normatively concerning turn in judicial practice. IoIs are judicial statements which, either explicitly or by implication, indicate that primary legislation is incompatible with certain protected human rights or civil liberties. They are related to, but stop short of, the formal remedies known as declarations of inconsistency (“DoIs”).
AbstractThis paper explores the effect that conformity to the rule of law has on the ends which might legitimately be pursued within a legal system. The neat distinction between formal and substantive conceptions of the rule of law will be challenged: even apparently formal conceptions necessarily affect the content of law and necessarily entail the protection of certain fundamental rights. What remains of the formal/substantive dichotomy is, in fact, a distinction between conceptions of the rule of law which guarantee the substantive justice of each and every law and those which entail some commitment to basic requirements of justice while nevertheless leaving room for unjust laws. Ultimately, the only significant distinction between competing theories of the rule of law concerns the nature of the connection between legality and justice, not whether there is any such connection at all.