Anthrax prophylaxis: recent advances and future directions

Anthrax is a serious, potentially fatal disease that can present in four distinct clinical patterns depending on the route of infection (cutaneous, gastrointestinal, pneumonic or injectional), so that effective strategies for prophylaxis and therapy are therefore required. Anthrax is a serious disease, requiring effective strategies for prophylaxis and therapy. This review addresses the complex mechanisms of pathogenesis employed by the bacterium and describes how, as understanding of these has developed over many years, so too have current strategies for vaccination and therapy. It covers the clinical and veterinary use of live attenuated strains of anthrax and the subsequent identification of protein sub-units for incorporation into vaccines, as well as combinations of protein sub-units with spore or other components. It also addresses the application of these vaccines for conventional prophylactic use, as well as post-exposure use in conjunction with antibiotics. It describes the licensed acellular vaccines AVA and AVP and discusses the prospects for a next generation of recombinant sub-unit vaccines for anthrax, balancing the regulatory requirement and current drive for highly defined vaccines, against the risk of losing the ‘danger’ signals required to induced protective immunity in the vaccinee. It considers novel approaches to reduce time to immunity by means of combining, for example, dendritic cell vaccination with conventional approaches and considers current opportunities for the immunotherapy of anthrax

Grammars of liberalism

Taras Fedirko would like to acknowledge funding from the British Academy (grant no. PF20/100094) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 683033).Liberalism has been fundamental to the making of the modern world, at times shaping basic assumptions as to the nature of the political, and in other cases existing as a delimited political project in contention with others. Across its long history, liberal projects have taken a diverse range of forms, which resist easy reduction to a single logic or history. This diversity, however, has often escaped anthropological attention. In this introduction to our special section on Grammars of Liberalism, we briefly trace this historical diversity, interrogate anthropological approaches to conceptualizing liberalism, and offer a broad framework for studying liberalism which remains attentive to both continuity and difference. Firstly, we argue for attention to how the political claims made by liberal projects unfold at the levels of values, their interrelations (morphology), and the underlying rules governing the expression and combination of values, and their intelligibility as liberal (grammar). Secondly, we argue for empirical attention to how values are expressed and liberal projects assembled across different social forms. We argue that this approach enables anthropology to grasp the diversity of liberal political projects and subject positions while still allowing scholars to approach liberalism critically and to interrogate its underlying logics.Publisher PDFNon peer reviewe

Transylvanian Baroque: Liberalism and its Others in Rural Romania

This thesis is an exploration of liberalism in Romania and in anthropology. Liberalism is frequently represented in contemporary anthropology as a hegemonic technocratic practice, rationalist ideology and hypocritically exclusionary politics. I challenge this representation through an ethnography of a British-Romanian rural revitalisation and conservation programme in the Saxon villages region of southern Transylvania, Romania, and the vernacular liberalism of the cosmopolitan youth who have taken this project up. Douglas Holmes has asserted that in the European Union (EU) in the twenty-first century, communities and people are experimenting with new identity projects that fuse the liberal and illiberal in innovative ways. I trace how the rural revitalisation programme brought together romantic, “integralist” visions of the Saxon villages with the EU’s liberal technologies of governance to create a set of projects the value of which could be translated between diverse sets of actors, from British tourists through European bureaucrats and Transylvanian farmers. This provided local youth with the possibility of making a life in their home region in a context of significant economic decline and massive emigration. The seemingly disparate liberal and romantic elements, initially brought together in a transnational context, were “domesticated” by Transylvanian liberals as complementary resources that could be mobilised to combat entrenched problems of Romanian society and modernity, as liberals saw it, notably the failure of the state to provide key services and the stagnation of the public sphere. The state’s failures had led liberals to abandon it is a source of hope, turning instead to voluntary action, which made the dilemmas of how to mobilise engaged publics all the more crucial. Village liberals’ attempts to foster such publics frequently ended up reproducing their own marginality, however. Against conventional representations of liberalism, I argue that its technocratic pretensions can be an object of hope in a milieu where expertise is perceived to be absent as much as an institutional hegemony. I further conclude that the multiple ways in which the liberal and the romantic are combined challenges dominant images of liberal ideology and practice as purely abstract and formal.Research supported by funding from the Newton Trust and Pigott Trust, via CHESS (Cambridge Home and European Scholarship Scheme)

Fife Local Energy Masterplan

The way we generate and use energy has constantly changed. In recent decades it has become the role of the National Grid, gas network, and multinational energy companies to deliver nearly all the energy: heat, electricity and transport fuels. We interact with energy via familiar light switches, gas boilers and petrol stations. In the future, delivery of and demand for energy in Scotland will be transformed. The Scottish Government’s ambition is to see an increasing number of new sustainable energy and district heating networks developed across the country to make the best use of natural energy sources including unused and renewable heat. This can help cut carbon emissions, reduce fuel bills and combat fuel poverty. Energy Masterplanning can assist developers and local authorities plan this process better, provide for ‘future proofing’ for communities and assist in using energy more efficiently

Tyrosine Phosphorylation of Tau by the Src Family Kinases Lck and Fyn

<p>Abstract</p> <p>Background</p> <p>Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease, where it is hyperphosphorylated on serine and threonine residues, and recently phosphotyrosine has been demonstrated. The Src-family kinase Fyn has been linked circumstantially to the pathology of Alzheimer's disease, and shown to phosphorylate Tyr18. Recently another Src-family kinase, Lck, has been identified as a genetic risk factor for this disease.</p> <p>Results</p> <p>In this study we show that Lck is a tau kinase. <it>In vitro</it>, comparison of Lck and Fyn showed that while both kinases phosphorylated Tyr18 preferentially, Lck phosphorylated other tyrosines somewhat better than Fyn. In co-transfected COS-7 cells, mutating any one of the five tyrosines in tau to phenylalanine reduced the apparent level of tau tyrosine phosphorylation to 25-40% of that given by wild-type tau. Consistent with this, tau mutants with only one remaining tyrosine gave poor phosphorylation; however, Tyr18 was phosphorylated better than the others.</p> <p>Conclusions</p> <p>Fyn and Lck have subtle differences in their properties as tau kinases, and the phosphorylation of tau is one mechanism by which the genetic risk associated with Lck might be expressed pathogenically.</p

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials

A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition

Little is known regarding the basis for selection of the semi-invariant αβ T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d–glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3β composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR α- and semi-invariant β-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved “hot spot” that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3β loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR–CD1d–glycolipid interaction in which the invariant CDR3α loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant αβ TCR and the unique antigen specificity of NKT cells