Dying in a terminal society: a response to Maung.

Maung argues that an externalist understanding of mental disorder exposes how, if society was more just for the most deprived, patterns of access to assisted dying might be different. I counter that reducing inequality lacks relevance to the immediate permissibility of assisted dying for mental disorder, owing to the need for solutions for those in distress. I suggest that the question of assistance in death for mental disorders is one of pragmatic politics, not for obfuscatory philosophy.

Coercion in psychiatry: is it right to involuntarily treat inpatients with capacity?

Psychiatric inpatients with capacity may be treated paternalistically under the Mental Health Act 1983. This violates bodily autonomy and causes potentially significant harm to health and moral status, both of which may be long-lasting. I suggest that such harms may extend to killing moral persons through the impact of psychotropic drugs on psychological connectedness. Unsurprisingly, existing legislation is overwhelmingly disliked by psychiatric inpatients, the majority of whom have capacity. I present four arguments for involuntary treatment: individual safety, public safety, authentic wishes and protection of autonomy. I explore these through a case study: a patient with schizophrenia admitted to a psychiatric hospital under the Mental Health Act 1983 after an episode of self-poisoning. Through its discussion of preventative detention, the public safety argument articulates the (un)ethical underpinnings of the current position in English law. Ultimately, none of the four arguments are cogent-all fail to justify the current legal discrimination faced by psychiatric inpatients. I conclude against any use of involuntary treatment in psychiatric inpatients with capacity, endorsing the fusion approach where only psychiatric patients lacking capacity may be treated involuntarily.

Enhanced replication of R5 HIV-1 isolates in†vitro by a small-molecule reagent targeting HIV-1 protease.

CHEMICAL ENHANCEMENT: Designed to target HIV-1 protease, a novel γ-hydroxyphosphonate has been found to significantly enhance viral replication in a panel of clinically relevant R5 HIV-1 isolates. This unexpected result constitutes the first instance of a small molecule capable of doing this, and it has implications for the preparation and use of R5 isolates in vaccine and drug development.

Organophosphorus compounds: intervention in mechanisms of signal transduction relevant to proliferative, immunological and circulatory disorders.

Literature publications reporting the development of organophosphorus compounds, targeting aspects of signal transduction to the titled therapeutic ends, are reviewed. With respect to extracellular targets, the development of ligands to purinergic (P2), and endothelial differentiation-gene receptors (of S1P- and LPA-receptor subtypes) is charted, along with inhibitors of the production and release of tumour necrosis factor-alpha (TNF-alpha). Reported also are inhibitors of the ectoenzymes aminopeptidase N, aminopeptidase A and dipeptidyl peptidase IV, the proteolytic enzyme thrombin, ligands to "apoptosis-receptors" and gammadelta T-cell activators. In addition, disruption of intracellular signalling chains mediated through reversible coupling of proteins via phosphorylation of Tyr residues and docking of pTyr residues in SH2-binding domains is covered. In particular, the development of ligands to SH2-binding domains in tyrosine kinases Src and lck, adaptor protein Grb2, and also ZAP70 protein are reported along with inhibitors to relevant phosphatases. SAR studies of ligands to Ins(1,4,5)-P3- and ryanodine-type receptors of intracellular Ca2+-storage organelles are described including analogues to secondary messengers cyclic-ADP-ribose (cADPR) and myo-inositol-1,4,5-triphosphate. Inhibitors of phosphatidyl inositol 3-kinase (PI3K) and sphingomyelinase are also reported, as are inhibitors of farnesyl transferase, the enzyme involved in protein-prenylation.