Antimicrobial resistance (AMR) poses an increasing threat to patient care and population health and there is a growing need for novel therapies to tackle AMR. Bacteriophage (phage) therapy is a re-emerging antimicrobial strategy with the potential to transform how bacterial infections are treated in patients and populations. Currently, in the UK, phages can be used as unlicensed medicinal products on a ‘named-patient’ basis. We make an ethical case for why it is crucially important for the UK to invest in Good (...) Manufacturing Practice (GMP) for both ongoing unlicensed and future licensed phage therapy. Access to phages produced to GMP (GMP phages) will ensure effective patient care and better outcomes as well as health systems benefits. The UK also has the potential to become a global leader in the timely and cost-efficient manufacturing and supply of a therapy that meets internationally recognised standards. (shrink)

In a number of membrane-bound viruses, ion channels are formed by integral membrane proteins. These channel proteins include M2 from influenza A, NB from influenza B, and, possibly, Vpu from HIV-1. M2 is important in facilitating uncoating of the influenza A viral genome and is the target of amantadine, an anti-influenza drug. The biological roles of NB and Vpu are less certain. In all cases, the protein contains a single transmembrane α-helix close to its N-terminus. Channels can be formed by (...) homo-oligomerization of these proteins, yielding bundles of transmembrane helices that span the membrane and surround a central ion-permeable pore. Molecular modeling may be used to integrate and interpret available experimental data concerning the structure of such transmembrane pores. This has proved successful for the M2 channel domain, where two independently derived models are in agreement with one another, and with solid-state nuclear magnetic resonance (NMR) data. Simulations based on channel models may yield insights into possible ion conduction and selectivity mechanisms. BioEssays 20:992–1000, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

I am interested in extending modal calculi by adding propositional quantifiers, given by the rules for quantifier introduction: provided that p does not occur free in A.

The author's motivation for constructing the calculi of this paper\nis so that time and tense can be "discussed together in the same\nlanguage" (p. 282). Two types of enriched propositional caluli for\ntense logic are considered, both containing ordinary propositional\nvariables for which any proposition may be substituted. One type\nalso contains "clock-propositional" variables, a,b,c, etc., for\nwhich only clock-propositional variables may be substituted and that\ncorrespond to instants or moments in the semantics. The other type\nalso contains "history-propositional" variables, u,v,w, etc., for\nwhich only history-propositional variables may (...) be substituted and\nthat correspond to maximally linearly ordered subsets of instants.\nThis second type is for tense logics in which time is not linear\nand where at any moment there may exist alternative future courses\nof events. Quantifiers are included in both types but only for clock-\nand history-propositional variables. However, these quantifiers are\ngiven an essentially substitutional interpretation. In addition,\nbesides each clock-propositional variable being true at exactly one\ninstant, the semantics requires that for each instant there be at\nleast one clock-propositional variable true at that instant, which\nin effect amounts to having each instant of the model "denoted" in\nthe formalism by some clock-propositional variable. Thus it is not\nsurprising that quantification over clock-propositional variables\nturns out to have a "well behaved first-order semantics" (p. 284).\n{One axiom relating history- with clock-propositions seems to need\nrevision: CKTauTbuAUabUba. Since the clock-propositional variables\nmight be true at the same instant the consequent should include an\nalternative, namely, LCab.} Besides the standard truth-functional\nand tense operators G,H,F,P, the author includes L for "it is\nalways the case that". The model-theoretic earlier-than relation\nordering instants and the semantic truth-at (an instant) relation\nare formalized by Uab and Taα (for a wff α) which\nare defined respectively as LCbPa (whenever the clock-proposition\nb is the case the clock-proposition a was the case) and LCaα\n(α is the case whenever the clock-proposition a is the case).\nBecause the future tense operators are definable in terms of U\nand T and the latter are definable in terms of L and P, the\ndual of H, the author notes that his completeness proofs can be\nrestricted to L and H as primitive and with the future tense\noperators used for other interpretations, especially Prior, A.'s\nindeterminist "it will be the case that", where time is not linear.\nThe author concludes with some rather technical observations showing\nthat "in ordinary tense logics the instants are nonstandard elements\nof the models. This provides", according to the author, "a semantic\npressure to build the instants into tense logic, so that they will\nappear as standard elements in the models" (p. 283). (shrink)

In [1, §4], my ‘proof’ that GH1 has the finite model property is incorrect; there are considerable obscurities towards the end of §1, particularly on p. 33; and I should have exhibited the finite models for GH1. In §1 of this paper I expand the analysis of the sub-directly irreducible models for GH1 which I give in §1 of [1]. In §2 I give a correct proof that GH1 has the finite model property. In §3 I exhibit these finite models (...) as models on certain ordered sets. (shrink)

Objective: To determine the views of people with multiple sclerosis (MS) and professionals in relation to confidentiality, consent and access to data within a proposed MS register in the UK. Design: Qualitative study using focus groups (10) and interviews (13). Setting: England and Northern Ireland. Participants: 68 people with MS, neurologists, MS nurses, health services management professionals, researchers, representatives from pharmaceutical companies and social care professionals. Results: People with MS expressed open and altruistic views towards the use of their personal (...) information to facilitate service provision and research, placing trust in responsible guardianship and legitimate use of their information. Participant’s proposed that people with MS should be able to select their individual level of involvement in a register using levels of consent. It was agreed that access to the register should be governed by a guardianship committee composed of a range of stakeholders. People with MS did not wish their details to be used by marketing agencies and did not consider this a legitimate use of their data. Whilst participants were positive of the role a register could play in promoting research, participants felt that access to data by pharmaceutical industries should be administered by the guardianship committee. People with MS are concerned should their employers be able to access their personal information. Professionals were more cautious than people with MS in their approach to the use of patient personal data within a register. Conclusions: Whilst all stakeholders were positive of the benefits of an MS register, development of such a resource must incorporate robust data security and guardianship measures in order to ensure that, whilst opportunities are maximised, risks to the privacy of individuals and legal challenges to professionals are avoided. (shrink)

Seeking consent for genetic and genomic research can be challenging, particularly in populations with low literacy levels, and in emergency situations. All of these factors were relevant to the MalariaGEN study of genetic factors influencing immune responses to malaria in northern rural Ghana. This study sought to identify issues arising in practice during the enrolment of paediatric cases with severe malaria and matched healthy controls into the MalariaGEN study.