Adversarialism in informal, collaborative, and 'soft' inquisitorial settings : lawyer roles in child welfare legal environments

This article explores the challenges and benefits of increased legal representation in child welfare hearings, with reference to the Scottish Children’s Hearings System. We look at the role and impact of adversarial behaviours within legal environments intended to follow an informal, collaborative approach. We analyse the views of 66 individuals involved in the Hearings System, including reporters, social workers, panel members and lawyers, collected through four focus groups and 12 interviews held in 2015. We place this analysis in the context of previous research. Our findings identify concern about adversarialism, inter-professional tensions and various challenges associated with burgeoning legal representation. Difficulties stem from disparate professional values and perceived threats to the ethos of hearings. We conclude it is difficult, but possible, to incorporate an adversarial element into such forums. Doing so may help to protect rights and potentially improve decision-making for children and families. The article concludes by considering implications for the practice of lawyers and others

Synthesis and antimalarial evaluation of artesunate-polyamine and trioxolane-polyamine conjugates

A series of artesunate-polyamine and trioxolane-polyamine conjugates have been prepared. The conjugates were evaluated for antimalarial activity towards the K1 dual drug resistant and NF54 chloroquine-sensitive strains of Plasmodium falciparum (Pf) and for cytotoxicity towards the rat myoblast cell line L6. (Bis)-Boc-(bis)-artesunate-polyamine and (tetra)-artesunate-polyamine conjugates exhibited potent in vitro activity towards both strains of Pf, with IC50 values in the range of 0.3-1.1 nM, comparable to the parent artesunate. Cytotoxicity within this series of analogues typically increased with polyamine (PA) chain length, identifying the PA3-4-3 (spermine), and to some extent the PA3-7-3 series, as being highly selective towards the parasite. The corresponding series of (bis)-Boc-(bis)-trioxolane and (tetra)-trioxolane-polyamine conjugates were less active as antimalarials than the parent trioxolane acid, highlighting the limitation of using this warhead for drug-conjugate studies. Preliminary in vivo evaluation of two artesunate-polyamine conjugates 11 and 16 demonstrated 95.5-99.8% reduction in parasitaemia with maximal 30 day survival rates (ip delivery). Oral testing of 11 proved less efficacious, with 95.7% activity and inconsistent survival rates of 16-30 days. In contrast, trioxolane-polyamines were substantially less effective (ip delivery), exhibiting only modest reductions in parasitaemia and modest to no increase in survival rates

Enantiomeric Variability of Distaminolyne A. Refinement of ECD and NMR Methods for Determining Optical Purity of 1-Amino-2-Alkanols

Sample configurations of distaminolyne A (1a); isolated from the ascidians Pseudodistoma opacum and P. cereum, and collected at different sites in New Zealand, were investigated by two methods: Exciton coupled electronic circular dichroism (EC ECD) of the corresponding N,O-dibenzoyl derivative 1b; and chiral reagent derivatization of 1a with (S)- and (R)-α-methoxyphenylacetic acid (MPA), followed by 1H-NMR analysis. Configuration and optical purity of 1a (%ee) was found to vary depending on the geographic distribution of ascidian colonies. An improved method for preparing N,O-diarenoyl derivatives of 1a was optimized. The EC ECD method was found to be complementary to the MPA-NMR method at different ranges of %ee

Synthesis and in vitro and in vivo evaluation of antimalarial polyamines

We recently reported that 1,14-diphenylacetamide derivatives of spermine exhibit potent nM in vitro growth inhibition properties of Plasmodium falciparum. In an effort to expand the structure-activity relationship of this compound class towards malaria, we have prepared and biologically tested a library that includes benzamide and 3-phenylpropanamide 'capping acid' groups, and polyamines that include spermine (PA3-4-3) and chain extended analogues PA3-8-3 and PA3-12-3. 2-Hydroxy and 2,5-dimethoxy analogues were typically found to exhibit the most potent activity towards the dual drug resistant strain K1 of P. falciparum with IC50's in the range of 1.3-9.5 nM, and selectivity indices (SI) of 42,300 to 4880. In vivo evaluation of three analogues against Plasmodium berghei was undertaken, with one demonstrating a modest 27.9% reduction in parasitaemia

Total Synthesis of (−)-Bicubebin A, B, (+)-Bicubebin C and Structural Reassignment of (−)-<i>cis</i>-Cubebin

The first total synthesis of (−)-bicubebin A, and two previously unreported dilignans, (−)-bicubebin B and (+)-bicubebin C has been achieved through the dimerization of (−)-cubebin, confirming the structure and absolute stereochemistry of (−)-bicubebin A. Analysis of the data for (−)-bicubebin B showed it matched that of reported compound (−)-<i>cis</i>-cubebin. The NMR data of the subsequently synthesized proposed structure of <i>cis</i>-cubebin confirmed that its original proposed structure was incorrect

Repurposing Primaquine as a Polyamine Conjugate to become an Antibiotic Adjuvant

International audienceIn our search for new antibiotic adjuvants as a novel strategy to deal with the emergence of multi-drug resistant (MDR) bacteria, a series of succinylprimaquine-polyamine (SPQ-PA) conjugates and derivatives of a cationic amphiphilic nature have been prepared. Evaluation of these primaquine conjugates for intrinsic antimicrobial properties and the ability to restore the antibiotic activity of doxycycline identified two derivatives, SPQ-PA3-8-3 and SPQ-PA3-10-3 that exhibited moderately strong intrinsic activity against the Gram-positive bacteria Staphylococcus aureus and the yeast Cryptococcus neoformans. None of the analogues were active against the Gram-negative bacterium Pseudomonas aeruginosa. However, in the presence of a sub-therapeutic amount of doxycycline (4.5 µM), both SPQ-PA3-4-3 and the SPQ-PA3-10-3 displayed potent antibiotic adjuvant properties against P. aeruginosa, with MIC's of 6.25 µM. A series of derivatives were prepared to investigate the structure-activity relationship that explored the influence of both a simplified aryl lipophilic substituent and variation of the length of the polyamine scaffold on observed intrinsic antimicrobial properties and the ability to potentiate the action of doxycycline against P. aeruginosa