Some kinetic and equilibrium studies of σ-adduct formation and proton transfer in the reactions of aromatic nitro-compounds with bases

Comparison of kinetic and equilibrium data for the cyclisation of 1-(2,2-dimethyl-3-hydroxypropoxy)-2,4-dinitro- naphthalene in alkaline media with those for the cyclisation of 1-(3-hydroxypropoxy)-2,4-dinitronaphthalene indicates the absence of a marked gem-dimethyl effect. (^1)H n.m.r. and visible spectral measurements show that alkoxide addition to 2,2’4,4’,6,6’-hexanitrobibenzyl (HNBB) and 2,2’,4,4’,6,6’-hexanitrostilbene (HNS) gives σ-adducts. Formation of the 3-(3’-) adduct is kinetically preferred but the 1-(1’-) adduct is thermodynamically more stable. In media of high basicity the 1:2 adduct with alkoxide addition at the 1- and 1’- positions is observed. For HNS a third interaction occurs which may be alkoxide addition at the olefinic bond. Kinetic and equilibrium data are reported for the reactions with methoxide ions in methanol and ethoxide ions in ethanol and compared with data for related compounds. The interactions of aliphatic amines with 2,4,6-trinitro- benzyl chloride (TNBCl), HNBB, HNS and 2,4,6-trinitrophenetole (TNP) in dimethyl sulphoxide have been investigated using visible and (^1)H n.m.r. spectroscopic methods. Kinetic and equilibrium data are reported for the various processes observed. The reversible reactions of TNBCl with primary amines are found to be: rapid formation of the 3-adduct, followed by isomerisation to the thermodynamically more stable 1-adduct, followed by equilibration with the conjugate base formed by transfer of a side-chain proton. With the secondary amines piperidine and pyrrolidine, σ-adduct formation at the 1-position is not observed because the presence of two bulky groups at the 1-position is sterically unfavourable. The σ-adduct forming reactions occur via zwitterionic intermediates and it is shown that proton transfers between these species and amines may be kinetically significant. The reactions of HNBB and HNS with amine also involve the initial formation of 3-adducts and 1-adducts. At high amine concentrations di-adducts may be formed by reaction of the 1- and 1’- or 3- and 3’- positions. A slow reaction of HNBB with amines gives a blue species which is shown to be a dianion formed by loss of two methylene protons. The slow step-in this reaction is shown to be rate limiting proton transfer from the substrate or from l:lσ-adducts. TNP reacts with primary and secondary amines to give isomeric σ-adducts at the 3-position and 1-position. Nucleophilic substitution involves general acid catalysed expulsion of the ethoxy group and yields N-substituted picramides. Data are also reported for the reactions of TNBCl with hydroxide ions in water and 30:70 (v/v) DMSO-water, of TNBCl with hydroxide ions in mixed (methanol-water-tetrahydrofuran) solvents, of HNBB with sulphite ions and of 1,3,5-trinitrobenzene with thioglycollic acid in water

Preparing to work in level 2 BIM: an innovative approach to a training and educational need

The well-known (probably the best known) objective of the UK Government’s 2011 Construction Strategy was for ‘fully collaborative 3D BIM (with all project and asset information, documentation and data being electronic) as a minimum by 2016’. This deadline has passed, and a number of reports have followed, commenting on how far the construction industry has progressed in its response. It is clear that some organisations consider themselves to be well-advanced in terms of their digital capabilities, whilst others lag behind. What should be remembered though, is that meeting this objective is not only about the software capabilities of individuals and their firms, but about BIM collaboration within projects. The paper outlines an innovative training offering that prepares project teams for working in such an environment. Virtual Project is a structured 3-day course that offers, to senior and middle management, the experience of multi-disciplinary collaboration, exploring as the ‘8 pillars’ of guidance for working at Level 2 BIM and experiencing some of the available technology for the design, construction and operation of built assets. Case studies are presented that illustrate the development of Virtual Project and responses from the participants, and the outcomes are mapped against the UK Government’s Learning Outcomes Framework, as well as the published work of the BIM Academic Forum. There are reflections on the challenges encountered, such as running the course overseas, and opportunities, such as its delivery in an e-learning environment

Territorialising movement: the politics of land occupation in Bangladesh

This paper considers the politics of land occupation in Bangladesh. Contentious politics have been conceptualised as 'societies in movement' by Raul Zibechi, defined through their attempts to disperse power through the reconfiguration of social relations between peasants, the state and capital. Drawing on the author's ethnographic engagement with peasant farmer movements in Bangladesh since 2002, the paper analyses the differential powers generated in, by and through the production of relations and connections involved in land occupations. This requires a consideration of both relational and structural understandings of contentious politics. Organisational structures and dynamics, as well as the 'resourcefulness' of social movements (e.g. their capacities to deploy material resources, skills and knowledges), enable land occupation since these are crucial in creating and maintaining the socio-material relations necessary for political activity to be prosecuted. Drawing together these insights, the paper conceptualises land occupation as a process of 'territorialising movement' articulated through three interwoven spatial practices: strategic occupation, reconfiguration of social relations and territorialisation of translocal solidarities

Changes in suspected adverse drug reaction reporting via the Yellow Card scheme in Wales following the introduction of a National Reporting Indicator

AIMS: This study aimed to assess the impact of a National Reporting Indicator (NRI) on rates of reporting of suspected adverse drug reactions using the Yellow Card scheme following the introduction of the NRI in Wales (UK) in April 2014. METHODS: Yellow Card reporting data for general practitioners and other reporting groups in Wales and England for the financial years 2014–15 (study period 1) and 2015–16 (study period 2) were obtained from the Medicines and Healthcare Products Regulatory Agency and compared with those for 2013–14 (pre‐NRI control period). RESULTS: The numbers of Yellow Cards submitted by general practitioners in Wales were 271, 665 and 870 in the control period, study period 1 and study period 2, respectively. This is equivalent to an increase of 145% in study period 1 and 221% in study period 2 compared with the 12‐month control period (2013–14). Corresponding increases in England were 17% and 37%, respectively (P < .001 chi–squared test). The numbers of Yellow Cards submitted by other groups in Wales were 906, 795 and 947 in each of the study periods. CONCLUSIONS: Introduction of the NRI corresponded with a significant increase in the number of Yellow Cards submitted by general practitioners in Wales. General practitioner reporting rates continued to increase year on year through to 2018–19 with the NRI still in place. No concomitant change was found in reporting rates by other groups in the health boards in Wales

Lanthanide Complexes that Respond to Changes in Cyanide Concentration in Water

Cyanide ions are shown to interact with lanthanide complexes of phenacylDO3A derivatives in aqueous solution, giving rise to changes in the luminescence and NMR spectra. These changes are the consequence of cyanohydrin formation, which is favored by the coordination of the phenacyl carbonyl group to the lanthanide center. These complexes display minimal affinity for fluoride and can detect cyanide at concentrations less than 1 μm. By contrast, lanthanide complexes with DOTAM derivatives display no affinity for cyanide in water, but respond to changes in fluoride concentration

Implementation of EAPs

This Research Note describes how to effectively implement employee assistance program services in an organization

Resourcing Scholar-Activism: Collaboration, Transformation, and the Production of Knowledge

In this article we offer a set of resources for scholar-activists to reflect on and guide their practice. We begin by suggesting that research questions should be triangulated to consider not only their scholarly merit but the intellectual and political projects the findings will advance and the research questions of interest to community and social movement collaborators

Antidepressant prescribing patterns and adverse events following introduction of a National Prescribing Indicator to monitor dosulepin usage in Wales

Aims: Limiting use of the antidepressant dosulepin has been encouraged due to associated risks of toxicity. In April 2011, the All Wales Medicines Strategy Group introduced a National Prescribing Indicator (NPI) to monitor dosulepin usage. The aim of this study was to investigate antidepressant prescribing patterns, and selected adverse events in patients prescribed dosulepin following introduction of the NPI. Methods: An e‐cohort study was conducted. Adult patients receiving regular dosulepin prescriptions between October 2010 and March 2011 were included. Characteristics of patients who were continued on dosulepin, were switched to an alternative antidepressant or whose dosulepin was discontinued following introduction of the NPI were compared. Results: In total, 4121 patients were included. Of these, 1947 (47%) continued dosulepin, 1487 (36%) were switched and 692 (17%) discontinued. Of the 692 who discontinued, 92% did not receive a prescription for another antidepressant during the follow‐up period. Patients whose dosulepin was discontinued were older and were less commonly coprescribed benzodiazepines. During follow‐up, recorded incidence of selected adverse events was low across all groups and no significant difference was observed. Conclusion: Over half of patients had discontinued dosulepin at the end of the period when the NPI was in place. Further interventions may have been required to have a greater impact on prescribing. This study provides some reassurance that dosulepin discontinuation can be a successful strategy, and that the risk of the adverse events investigated was unlikely to have been greater in those who had dosulepin discontinued than in those in whom dosulepin had been continued

Atypical Haemolytic Uraemic Syndrome Associated with a Hybrid Complement Gene

BACKGROUND: Sequence analysis of the regulators of complement activation (RCA) cluster of genes at chromosome position 1q32 shows evidence of several large genomic duplications. These duplications have resulted in a high degree of sequence identity between the gene for factor H (CFH) and the genes for the five factor H-related proteins (CFHL1–5; aliases CFHR1–5). CFH mutations have been described in association with atypical haemolytic uraemic syndrome (aHUS). The majority of the mutations are missense changes that cluster in the C-terminal region and impair the ability of factor H to regulate surface-bound C3b. Some have arisen as a result of gene conversion between CFH and CFHL1. In this study we tested the hypothesis that nonallelic homologous recombination between low-copy repeats in the RCA cluster could result in the formation of a hybrid CFH/CFHL1 gene that predisposes to the development of aHUS. METHODS AND FINDINGS: In a family with many cases of aHUS that segregate with the RCA cluster we used cDNA analysis, gene sequencing, and Southern blotting to show that affected individuals carry a heterozygous CFH/CFHL1 hybrid gene in which exons 1–21 are derived from CFH and exons 22/23 from CFHL1. This hybrid encodes a protein product identical to a functionally significant CFH mutant (c.3572C>T, S1191L and c.3590T>C, V1197A) that has been previously described in association with aHUS. CONCLUSIONS: CFH mutation screening is recommended in all aHUS patients prior to renal transplantation because of the high risk of disease recurrence post-transplant in those known to have a CFH mutation. Because of our finding it will be necessary to implement additional screening strategies that will detect a hybrid CFH/CFHL1 gene