Malaria vaccines 1985-2005: a full circle?

Few who were actively engaged in malaria vaccine research 20 years ago (including myself) would have imagined that, in 2005, there would still be a prediction of a 10-20-year horizon before vaccines become part of malaria-control strategies. Why is it still proving so challenging to produce effective vaccines

Activity in the pallial nerve of knobbed (Busycon carica) and channeled (Busycotypus canaliculatum) whelks recorded during exposure of the osphradium to odorant solutions

Adult horseshoe crabs (Limulus polyphemus) are the preferred bait in the U.S. east coast whelk pot fishery, but their harvest is being restricted because of severe population declines in the Chesapeake and Delaware bays. To identify other baits, the activity in the pallial nerve of whelks was determined during exposure of the osphradium to odorant solutions prepared from horseshoe crab eggs, horseshoe crab hemolymph, and hard clam (Mercenaria mercenaria) tissue. All three elicited significant responses; bait based on them may provide an alternative to the use of adult horseshoe crabs, although extensive behavioral testing remains to be done. Channeled whelk did not respond to molecular weight fractions (>3 kDa and <3 kDa) prepared from horseshoe crab egg odorant solutions but did respond when the molecular weight fractions were recombined. Whelks appear to have broadly tuned chemoreceptors and manufactured baits may need to mimic the complex mixture of odorants derived from natural sources

Impact of future HERA data on the determination of proton parton distribution functions using the ZEUS QCD fit

The high precision and large kinematic coverage of the data from the HERA-I running period (1994-2000) have already allowed precise extractions of proton parton distribution functions (PDFs). The HERA-II running program is now underway and is expected to provide a substantial increase in the luminosity collected at HERA. In this paper, a study is presented which investigates the potential impact of future data from HERA on the proton PDF uncertainties, within the currently planned running scenario. In addition, the effect of a possible future measurement of the longitudinal structure function, FL, on the gluon distribution is investigated.Comment: 5 pages, 2 figures, in proceedings of the XIII International Workshop on Deep Inelastic Scattering - DIS 2005, Madison, Wisconsin, 200

The polymorphs and solvates of phenylbutazone and their phase transition behaviour

In this study, which was conducted between March 2007 and December 2008, the crystal structure of the alpha polymorph of phenylbutazone has been determined by single crystal X-ray diffractometry. The present findings support those of Singh & Vijayan (1977) and Paradies (1987). Efforts to grow single crystals of the beta and delta polymorphs of phenylbutazone did not locate specimens of adequate quality for structure determination. Nonetheless it was possible to isolate high purity powder samples of these two forms. The powder diffraction pattern of the delta polymorph was measured with improved accuracy at the Diamond synchrotron, and reveals a number of peak overlaps in previously published diffraction patterns of this crystal form. The improved diffraction data have enabled the crystal system of the delta form to be identified as orthorhombic, and space-group selection has been narrowed down to Pnn2 or Pnnm. Four new solvated forms of phenylbutazone have been identified. The crystal structures of two of these new solvates have been determined by single crystal diffractometry. Both have space-group C2/c, and may be considered isostructural with five formerly identified solvates, whose structures were published by Hosokawa et al. in 2004. Previously phenylbutazone has been found to change polymorphic forms at above-ambient temperatures. This behaviour has been examined both in a differential scanning calorimeter and on a powder X-ray diffractometer equipped with isothermal sample heating, where the transition of the alpha and beta polymorphs to the delta polymorph was observed. Thermodynamic methods of predicting the transition temperatures of polymorphs are discussed, particularly those derived from dissolution data. In the case of phenylbutazone, a substantial amount of dissolution data has been collected elsewhere, and these data are used to generate computational predictions of the polymorphic transition temperatures for comparative purposes

Incidence and mechanism of the pivot shift. An in vitro study.

Accepted versio

Shrinking the Malaria Map: A Prospectus on Malaria Elimination

\ud Thirty-nine countries across the world are making progress toward malaria elimination. Some are committed to nationwide elimination, while others are pursuing spatially progressive elimination within their borders. Influential donor and multilateral organizations are supporting their goals of achieving malaria-free status. With elimination back on the global agenda, countries face a myriad of questions. Should they change their programs to eliminate rather than control malaria? What tools are available? What policies need to be put into place? How will they benefit from elimination? Unfortunately, answers to these questions, and resources for agencies and country program managers considering or pursuing elimination, are scarce. The 39 eliminating countries are all positioned along the endemic margins of the disease, yet they naturally experience a variety of country characteristics and epidemiologies that make their malaria situations different from one another. The Malaria Elimination Group (MEG) and this Prospectus recognize\ud that there is no single solution, strategy, or time line that will be appropriate for every country, and each is encouraged to initiate a comprehensive evaluation of its readiness and strategy for elimination. The Prospectus is designed to guide countries in conducting these assessments. The Prospectus provides detailed and informed discussion on the practical means of achieving and sustaining zero transmission. It is designed as a road map, providing direction and options from which to choose an appropriate path. As on all maps, the destination is clearly marked, but the possible routes to reach it are numerous. The Prospectus is divided into two sections: Section 1 Eliminating Malaria comprises four chapters covering the strategic components important to the periods before, during, and after an elimination program. Section 2 Tools for the Job, comprises six chapters that outline basic information about how interventions in an elimination program will be different from those in a control setting. Chapter 1, Making the Decision, evaluates the issues that a country should consider when deciding whether or not to eliminate malaria. The chapter begins with a discussion about the quantitative and qualitative benefits that a country could expect from eliminating malaria and then recommends a thorough feasibility assessment. The feasibility assessment is based on three major components: operational, technical, and financial feasibility. Cross-border and regional collaboration is a key subject in this chapter. Chapter 2, Getting to Zero, describes changes that programs must consider when moving from sustained control to an elimination goal. The key strategic issues that must be addressed are considered, including supply chains, surveillance systems, intersectoral collaboration, political will, and legislative framework. Cross-border collaboration is again a key component in Getting to Zero. Chapter 3, Holding the Line, provides recommendations on how to conduct an assessment of two key factors that will affect preventing the reemergence of malaria once transmission is interrupted: outbreak risk and importation risk. The chapter emphasizes the need for a strong surveillance system in order to prevent and, if necessary, respond to imported cases. Chapter 4, Financing Elimination, reviews the cost-effectiveness of elimination as compared with sustained control and then presents the costs of selected elimination programs as examples. It evaluates four innovative financing mechanisms that must support elimination, emphasizing the need for predictable and stable financing. Case studies from Swaziland and two provinces in China are provided. Chapter 5, Understanding Malaria, considers malaria from the point of view of elimination and provides a concise overview of the current burden of the disease, malaria transmission, and the available interventions that can be used in an elimination program. Chapter 6, Learning from History, extracts important lessons from the Global Malaria Eradication Program and analyzes some elimination efforts that were successful and some that were unsuccessful. The chapter also reviews how the malaria map has been shrinking since 1900. xiv A Prosp ectus on Mala ria Elimi natio n\ud Chapter 7, Measuring Malaria for Elimination, provides a precise language for discussing malaria and gives the elimination discussion a quantitative structure. The chapter also describes the role of epidemiological theory and mathematical modeling in defining and updating an elimination agenda for malaria. Chapter 8, Killing the Parasite, outlines the importance of case detection and management in an elimination setting. Options for diagnosis, the hidden challenge of Plasmodium vivax in an elimination setting, and the impact of immunity are all discussed. Chapter 9, Suppressing the Vector, explores vector control, a necessary element of any malaria program. It considers optimal methods available to interrupt transmission and discusses potential changes, such as insecticide resistance, that may affect elimination efforts. Chapter 10, Identifying the Gaps — What We Need to Know, reviews the gaps in our understanding of what is required for elimination. The chapter outlines a short-term research agenda with a focus on the operational needs that countries are facing today. The Prospectus reviews the operational, technical, and financial feasibility for those working on the front lines and considers whether, when, and how to eliminate malaria. A companion document, A Guide on Malaria Elimination for Policy Makers, is provided for those countries or agencies whose responsibility is primarily to make the policy decisions on whether to pursue or support a malaria elimination strategy. The Guide is available at www.malaria eliminationgroup.org

Coupled black hole and galaxy formation in the young universe

This thesis presents results from three major imaging studies designed to determine the properties of massive galaxies selected at high redshift. The most massive known galaxies at high redshift (i.e. radio galaxies), the most massive known starbursts at high redshift (i.e. submillimetre galaxies), and the most massive known black holes at high redshifts (i.e. quasars) have been targeted, with the aim of better establishing the relationship between these different classes of massive object.The results from deep K—band imaging of the most luminous radio galaxies at z ~ 2 and the brightest submillimetre sources in the 8- mjy survey are presented. Morphological properties are measured and compared to explore whether submillimetre hosts are the progenitors of today's most massive ellipticals. Two-dimensional modelling finds that the high-redshift radio galaxies have surface brightness distributions consistent with those expected for classic ellipticals (Sersic parameter, n = 4), with n in the range 2.5 = 4.04±0.27. In contrast, submillimetre galaxies are found to be disks (Sersic parameter, n = 1) with n in the range 1.0 < n < 2.5 and =1.46±0.16. The half-light radii of the radio hosts are distributed over a range 2 < r1/2 = 7.85 ± 1.2 kpc, while submillimetre sources are smaller, with 1 = 3.15 ± 0.29 kpc. The z ~ 2 radio galaxies are found to be, on average, a factor ~ 2 smaller than massive radio galaxies at z < 1 and follow a Kormendy (/ie — re) relation similar to that of 3C-type galaxies at low redshift after evolutionary corrections, assuming a burst-formation model at z = 3, consistent with the median redshift of the submillimetre sources. The luminosities of the submillimetre galaxies are ~ 1.5 magnitudes brighter than Lyman-break galaxies at comparable redshifts, indicating that submillimetre galaxies are significantly more massive. Finally, surface mass densities for both source types are found to be consistent with quiescent elliptical galaxies at high redshift, and not star-forming or Lyman-break galaxies.The results are presented of a study that uses the 3CRR sample of radio-loud ac¬ tive galactic nuclei to investigate the evolution of the black-hole:spheroid mass ratio in the most massive early-type galaxies from 0 < z < 2. Radio-loud unification is ex¬ ploited to obtain virial (linewidth) black hole mass estimates from the 3CRR quasars, and stellar mass estimates from the 3CRR radio galaxies, thereby providing black hole and stellar mass estimates for a single population of early-type galaxies. At low redshift (z<l) the 3CRR sample is consistent with a black-hole:spheroid mass ratio of Mbh/Mbulge ~ 0.002, in good agreement with that observed locally for quiescent galaxies of similar stellar mass (Mbuige — 5 x 10u M0). However, over the redshift interval 0 < z < 2 the 3CRR black-hole:spheroid mass ratio is found to evolve as Mbh/Mbuige oc (1 + z)2-07±0-76/ reaching Mbh/Mbulge ~ 0.008 by redshift z ~ 2. If con¬ firmed, the detection of evolution in the 3CRR black-hole:spheroid mass ratio further strengthens the evidence that, at least for massive early-type galaxies, the growth of the central supermassive black hole may be completed before that of the host spheroid.The results from an ongoing project to constrain the evolution of the blackhole:spheroid mass ratio at z — 3,4 are presented. At these redshifts, quasars and their hosts provide a unique window on this evolution, as the only class of object in which both galaxy and black hole masses can be directly measured. Additionally, the black-hole:bulge mass ratios of flat spectrum quasars at z ~ 1.5 are used to deter¬ mine whether the BLR in AGN possesses a spherical or disk-like morphology. It is demonstrated that both black hole and host galaxy masses can be obtained from emis¬ sion linewidths and deep high-quality A-band imaging respectively. These pilot data represent the first attempt to constrain the black-hole:spheroid mass ratio as part of a statistically significant sample at z = 3,4, a crucial epoch of galaxy formation and evolution