Precaution, governance and the failure of medical implants: the ASR(TM) hip in the UK

Hip implants have provided life-changing treatment, reducing pain and improving the mobility and independence of patients. Success has encouraged manufacturers to innovate and amend designs, engendering patient hopes in these devices. However, failures of medical implants do occur. The failure rate of the Articular Surface Replacement metal-on-metal hip system, implanted almost 100,000 times world-wide, has re-opened debate about appropriate and timely implant governance. As commercial interests, patient hopes, and devices’ governance converge in a socio-technical crisis, we analyse the responses of relevant governance stakeholders in the United Kingdom between 2007 and 2014. We argue that there has been a systemic failure of the governance system entrusted with the safety of patients fitted with medical implants. Commercial considerations of medical implants and the status quo of medical implant governance have been given priority over patient safety despite the availability of significant failure data in an example of uncertainty about what constitutes appropriate precautionary action

Stressor Effects of High Relative Humidity and a High Moisture Diet on appearance of Disease from Nuclear Polyhedrosis Virus in Larvae of Porthetria Dispar (L.)

High relative humidity (R.H.) and a high moisture diet were tested as stressors in the incidence of nuclear polyhedrosis virus (NPV) disease of larvae of Porthetria dispar (L.). Relative humidity was shown to have no effect on the appearance of NPV disease in larvae reared in the laboratory. However, a high mortality from other causes was sustained by a group of larvae subjected to both high R.H. and a high moisture diet. The absence of NPV disease during the first larval instar period confirmed earlier findings that effective egg sanitization virtually eliminates NPV disease. This supports current disfavor with the theory of transovarial transmission of P. dispar NPV. One case of NPV disease was found in a late instar larva. This may be attributed to incomplete sanitization of its egg, or to later contamination. The problems encountered here in studying latent viral disease, and in pinpointing the roles of certain environmental conditions as stressors, parallel similar obstacles to the study of stressor action and latency in human disease. The nature of insect nuclear polyhedrosis virus is discussed, as well as the potential effects on public and environmental health of its use as a viral insecticide

Recent range expansion of an intermediate host for animal schistosome parasites in the Indo-Australian Archipelago: phylogeography of the freshwater gastropod Indoplanorbis exustus in South and Southeast Asia

Background: The planorbid snail Indoplanorbis exustus is the sole intermediate host for the Schistosoma indicum species group, trematode parasites responsible for cattle schistosomiasis and human cercarial dermatitis. This freshwater snail is widely distributed in Southern Asia, ranging from Iran to China eastwards including India and from the southeastern Himalayas to Southeast Asia southwards. The veterinary and medical importance of this snail explains the interest in understanding its geographical distribution patterns and evolutionary history. In this study, we used a large and comprehensive sampling throughout Indo-Malaya, including specimens from South India and Indonesia, areas that have been formerly less studied. Results: The phylogenetic inference revealed five highly divergent clades (genetic distances among clades: 4.4–13.9%) that are morphologically indistinguishable, supporting the assumption that this presumed nominal species may represent a cryptic species complex. The species group may have originated in the humid subtropical plains of Nepal or in southern adjacent regions in the Early Miocene. The major cladogenetic events leading to the fives clades occurred successively from the Early Miocene to the Early Pleistocene, coinciding with major periods of monsoonal intensification associated with major regional paleogeographic events in the Miocene and repeated climate changes due to the Plio-Pleistocene climatic oscillations. Our coverage of the Indo-Australian Archipelago (IAA) highlights the presence of a single clade there. Contrary to expectations, an AMOVA did not reveal any population genetic structure among islands or along a widely recognised zoogeographical regional barrier, suggesting a recent colonisation independent of natural biogeographical constraints. Neutrality tests and mismatch distributions suggested a sudden demographic and spatial population expansion that could have occurred naturally in the Pleistocene or may possibly result of a modern colonisation triggered by anthropogenic activities. Conclusions: Even though Indoplanorbis is the main focus of this study, our findings may also have important implications for fully understanding its role in hosting digenetic trematodes. The existence of a cryptic species complex, the historical phylogeographical patterns and the recent range expansion in the IAA provide meaningful insights to the understanding and monitoring of the parasites potential spread. It brings a substantial contribution to veterinary and public health issues

New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: synthesis, anti-HIV-1 evaluation and binding affinities

CXCR4 is a target of growing interest for the development of new therapeutic drugs and imaging agents as its role in multiple disease states has been demonstrated. AMD3100, a CXCR4 chemokine receptor antagonist that is in current clinical use as a haematopoietic stem cell mobilising drug, has been widely studied for its anti-HIV properties, potential to inhibit metastatic spread of certain cancers and, more recently, its ability to chelate radiometals for nuclear imaging. In this study, AMD3100 is functionalised on the phenyl moiety to investigate the influence of the structural modification on the anti-HIV-1 properties and receptor affinity in competition with anti-CXCR4 monoclonal antibodies and the natural ligand for CXCR4, CXCL12. The effect of complexation of nickel(II) in the cyclam cavities has been investigated. Two amino derivatives were obtained and are suitable intermediates for conjugation reactions to obtain CXCR4 molecular imaging agents. A fluorescent probe (BODIPY) and a precursor for 18F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents

Transport in a three-terminal graphene quantum dot in the multi-level regime

We investigate transport in a three-terminal graphene quantum dot. All nine elements of the conductance matrix have been independently measured. In the Coulomb blockade regime accurate measurements of individual conductance resonances reveal slightly different resonance energies depending on which pair of leads is used for probing. Rapid changes in the tunneling coupling between the leads and the dot due to localized states in the constrictions has been excluded by tuning the difference in resonance energies using in-plane gates which couple preferentially to individual constrictions. The interpretation of the different resonance energies is then based on the presence of a number of levels in the dot with an energy spacing of the order of the measurement temperature. In this multi-level transport regime the three-terminal device offers the opportunity to sense if the individual levels couple with different strengths to the different leads. This in turn gives qualitative insight into the spatial profile of the corresponding quantum dot wave functions.Comment: 12 pages, 6 figure

Electron microscopic visualization of tRNA genes with ferritin-avidin: biotin labels

A method is described for indirect electron microscopic visualization and mapping of tRNA and other short transcripts hybridized to DNA. This method depends upon the attachment of the electron-dense protein ferritin to the RNA, the binding being mediated by the remarkably strong association of the egg white protein avidin with biotin. Biotin is covalently attached to the 3' end of tRNA using an NH2 (CH2) 5NH2 bridge. The tRNA-biotin adduct is hybridized to complementcrry DNA sequences present in a single stranded nonhomology loop of a DNA:DNA heteroduplex. Avidin, covalently crosslinked to ferritin is mixed with the heteroduplex and becomes bound to the hybridized tRNA-biotin. Observation of the DNA:RNA-biotin:avidin-ferritin complex by electron microsdopy specifically and accurately reveals the position of the tRNA gene, with a frequency of labeling of approximately 50%