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Superconducting curved magnets can reduce accelerator footprints by producing strong fields (>3 T) for applications such as carbon ion therapy, however the effect of strongly curved magnetic multipoles and fringe fields on accelerator beam dynamics is not fully understood. This is especially important for compact synchrotrons, where off-axis body fields and fringe fields can significantly affect beam qual-ity and long-term beam stability. To establish the effect of magnet curvature on higher order multipole fields and on beam stability, an electromagnetic model of a supercon-ducting, curved alternating- gradient canted-cosine-theta magnet (AG-CCT) is analysed. The magnet is studied for the main bending magnets in a 27 m circumference carbon ion therapy synchrotron, designed within the Next Ion Med-ical Machine Study (NIMMS) at CERN and the European project HITRIplus. The multipole fields of the magnet are implemented in a lattice model of the synchrotron in MAD-X/PTC to study long term beam stability, and to understand the effect of curved multipoles on particle dynamics for opti-misation of both the lattice and magnet designs. Preliminary assessment of the performance of the synchrotron finds that the AG-CCT multipoles are well-tolerated in the lattice. Re-sults are discussed for the suitability of the synchrotron for clinical application.

These notes provide an overview of Fixed-Field Alternating-Gradient (FFAG) accelerators for medical applications. We begin with a review of the basic principles of this type of accelerator, including the scaling and non-scaling types, highlighting beam dynamics issues that are of relevance to hadron ac- celerators. The potential of FFAG accelerators in the field of hadron therapy is discussed in detail, including an overview of existing medical FFAG designs. The options for FFAG treatment gantries are also considered., Notes composed for the 2015 CERN Specialised Accelerator School on Medical Accelerators. Submitted to CERN Yellow Reports series

This paper presents results on variability of out-turn shortfalls about the expected value indices which are usually presented in resource adequacy studies, for a range of Loss of Load Expectation (LOLE) levels and installed wind capacities in a test system generally representative of future Great Britain system scenarios. While the details of results will clearly vary between systems, one very general conclusion is possible. In the results presented, for a given LOLE level, the probability of very severe out-turn in a future peak season is much greater at high installed wind capacity. Thus for this system, as the installed wind capacity increases, a constant level of LOLE cannot be taken as an indicator of an unchanging overall risk profile of the system. This further demonstrates that in any system, LOLE cannot be assumed to be a good summary statistic of risk profile as the installed variable generation (VG) capacity increases, and that it might be necessary to reconsider the near-universal use of expected value risk indices as the main headline indices in utility adequacy studies.

In the absence of any highly effective vaccine candidate against Plasmodium falciparum malaria, it remains imperative for the field to pursue all avenues that may lead to the successful development of such a formulation. The development of a subunit vaccine targeting the asexual blood-stage of Plasmodium falciparum malaria infection has proven particularly challenging with only limited success to date in clinical trials. However, only a fraction of potential blood-stage vaccine antigens have been evaluated as targets, and a number of new promising candidate antigen formulations and delivery platforms are approaching clinical development. It is therefore essential that reliable and sensitive methods of detecting, or ruling out, even modest efficacy of blood-stage vaccines in small clinical trials be established. In this article we evaluate the challenges facing blood-stage vaccine developers, assess the appropriateness and limitations of various in vivo approaches for efficacy assessment and suggest future directions for the field.

This thesis describes the design a novel type of particle accelerator for charged particle therapy. The accelerator is called a non-scaling, Fixed Field Alternating Gradient (ns-FFAG) accelerator, and will accelerate both protons and carbon ions to energies required for clinical use. The work is undertaken as part of the PAMELA project. An existing design for a ns-FFAG is taken as a starting point and analysed in terms of its ability to suit the charged particle therapy application. It is found that this design is particularly sensitive to alignment errors and would be unable to accelerate protons and carbon ions at the proposed acceleration rate due to betatron resonance crossing phenomena. To overcome this issue, a new type of non-linear ns-FFAG is developed which avoids resonance crossing and meets the requirements provided by clinical considerations. Two accelerating rings are required, one for protons up to 250 MeV and fully stripped carbon ions to 68 MeV/u, the other to accelerate the carbon ions up to 400-430 MeV/u. Detailed studies are undertaken to show that this new type of accelerator is suitable for the application. An alignment accuracy of 50 micrometers will not have a detrimental effect on the beam and the dynamic aperture for most lattice configurations is found to be greater than 50 pi.mm.mrad normalised in both the horizontal and vertical plane. Verification of the simulation code used in the PAMELA lattice design is carried out using experimental results from EMMA, the world's first ns-FFAG for 10-20 MeV electrons built at Daresbury Laboratory, UK. Finally, it is shown that the described lattice can translate into realistic designs for the individual components of the accelerator. The integration of these components into the PAMELA facility is discussed.

The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1AMA1 - results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets. © The American Society of Gene and Cell Therapy.

Barlow R J: Huddersfield University Edgecock, T R: Huddersfield University Johnstone, C: FNAL Owen, H: Manchester University Sheehy, S L: STFC

PIP, the Proton Isotope Production accelerator, is a low\ud energy (6-10 MeV) proton nsFFAG design that uses a sim-\ud ple 4-cell lattice. Low energy reactions involving the cre-\ud ation of specific nuclear states can be used for neutron pro-\ud duction and for the manufacture of various medical iso-\ud topes. Unfortunately a beam rapidly loses energy in a target\ud and falls below the resonant energy. A recycling ring with\ud a thin internal target enables the particles that did not in-\ud teract to be re-accelerated and used for subsequent cycles.\ud The increase in emittance due to scattering in the target is\ud partially countered by the re-acceleration, and accommo-\ud dated by the large acceptance of the nsFFAG. The ring is\ud essentially isochronous, the fields provide strong focussing\ud so that losses are small, the components are simple, and it\ud could be built at low cost with existing technology.

Poster presented at Cyclotrons'13 Conference in Vancouver, September 2013. WEPPT031

Talk given for the Beam Dynamics meets Magnets Workshop in Darmstadt, Germany, 2-4th December 2013. The talk give an overview of the experience and interaction between beam dynamics and magnet design during the PAMELA project for an FFAG for hadron therapy.

BACKGROUND: Traditionally, vaccine development against the blood-stage of Plasmodium falciparum infection has focused on recombinant protein-adjuvant formulations in order to induce high-titer growth-inhibitory antibody responses. However, to date no such vaccine encoding a blood-stage antigen(s) alone has induced significant protective efficacy against erythrocytic-stage infection in a pre-specified primary endpoint of a Phase IIa/b clinical trial designed to assess vaccine efficacy. Cell-mediated responses, acting in conjunction with functional antibodies, may be necessary for immunity against blood-stage P. falciparum. The development of a vaccine that could induce both cell-mediated and humoral immune responses would enable important proof-of-concept efficacy studies to be undertaken to address this question. METHODOLOGY: We conducted a Phase Ia, non-randomized clinical trial in 16 healthy, malaria-naïve adults of the chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient viral vectored vaccines encoding two alleles (3D7 and FVO) of the P. falciparum blood-stage malaria antigen; apical membrane antigen 1 (AMA1). ChAd63-MVA AMA1 administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing high-level T cell responses to both alleles 3D7 (median 2036 SFU/million PBMC) and FVO (median 1539 SFU/million PBMC), with a mixed CD4(+)/CD8(+) phenotype, as well as substantial AMA1-specific serum IgG responses (medians of 49 µg/mL and 41 µg/mL for 3D7 and FVO AMA1 respectively) that demonstrated growth inhibitory activity in vitro. CONCLUSIONS: ChAd63-MVA is a safe and highly immunogenic delivery platform for both alleles of the AMA1 antigen in humans which warrants further efficacy testing. ChAd63-MVA is a promising heterologous prime-boost vaccine strategy that could be applied to numerous other diseases where strong cellular and humoral immune responses are required for protection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01095055.