Towards a Strategic Plan for Research to Support the Global Program to EIiminate Lymphatic FiIariasis: Summary of Immediate Needs and Opportunities for Research on Lymphatic Filariasis. 2.2 Essential tools – Drugs and Clinical Drug Trials

A series of advances during the past decade transformed LF from a neglected disease of poor countries into a disease now recognized as potentially eradicable. Principal among the reasons for these advances were the identification of ivermectin and albendazole as new, effective anti-filarial agents and the discovery of new virtues for an old anti-filarial drug, DEC (i.e., its single-dose efficacy and macrofilaricidal action). These discoveries were essential for the subsequent creation of the Global Program to Eliminate LF,1 whose very basis is the large-scale use of DEC, ivermectin (Mectizan�; Merck and Co., Inc., Rahway, NJ) and albendazole. Indeed, in many endemic countries literally millions of tablets of these drugs are distributed over a few short days each year (often on a single day), making GPELF the largest chemotherapy program ever undertaken. Currently it is just these three drugs that are available for use in single-dose, annual MDA programs. Albendazole is co-administered with ivermectin in areas of Africa and Yemen where LF and onchocerciasis are co-endemic. For all other LF-endemic regions, albendazole is co-administered with DEC. At the recommended dose levels, none of the drugs is completely macrofilaricidal, although all appear to inflict some lasting damage to adult worms. Both DEC and ivermectin kill mf efficiently; albendazole, on the other hand, has no direct effect on mf, but rather appears to suppress embryogenesis in the adult female worm. An alternative treatment strategy involving the use of DEC as a fortificant in table/cooking salt for a period of 1−2 years is currently used in just one country, but was a mainstay of the earlier, successful LF elimination program in China

Risk factors for mortality from imported falciparum malaria in the United Kingdom over 20 years: an observational study

Objectives To determine which travellers with malaria are at greatest risk of dying, highlighting factors which can be used to target health messages to travellers. Design Observational study based on 20 years of UK national data. Setting National register of malaria cases. Participants 25 054 patients notified with Plasmodium falciparum malaria, of whom 184 died, between 1987 and 2006. Main outcome measures Comparison between those with falciparum malaria who died and non-fatal cases, including age, reason for travel, country of birth, time of year diagnosed, malaria prophylaxis used. Results Mortality increased steadily with age, with a case fatality of 25/548 (4.6%) in people aged >65 years, adjusted odds ratio 10.68 (95% confidence interval 6.4 to 17.8), P<0.001 compared with 18–35 year olds. There were no deaths in the ≤5 year age group. Case fatality was 3.0% (81/2740 cases) in tourists compared with 0.32% (26/8077) in travellers visiting friends and relatives (adjusted odds ratio 8.2 (5.1 to 13.3), P<0.001). Those born in African countries with endemic malaria had a case fatality of 0.4% (36/8937) compared with 2.4% (142/5849) in others (adjusted odds ratio 4.6 (3.1 to 9.9), P<0.001). Case fatality was particularly high from the Gambia. There was an inverse correlation in mortality between region of presentation and number of cases seen in the region (R2=0.72, P<0.001). Most delay in fatal cases was in seeking care. Conclusions Most travellers acquiring malaria are of African heritage visiting friends and relatives. In contrast the risks of dying from malaria once acquired are highest in the elderly, tourists, and those presenting in areas in which malaria is seldom seen. Doctors often do not think of these as high risk groups for malaria; for this reason they are important groups to target in pre-travel advice

Are Simple Real Pole Solutions Physical?

We consider exact solutions generated by the inverse scattering technique, also known as the soliton transformation. In particular, we study the class of simple real pole solutions. For quite some time, those solutions have been considered interesting as models of cosmological shock waves. A coordinate singularity on the wave fronts was removed by a transformation which induces a null fluid with negative energy density on the wave front. This null fluid is usually seen as another coordinate artifact, since there seems to be a general belief that that this kind of solution can be seen as the real pole limit of the smooth solution generated with a pair of complex conjugate poles in the transformation. We perform this limit explicitly, and find that the belief is unfounded: two coalescing complex conjugate poles cannot yield a solution with one real pole. Instead, the two complex conjugate poles go to a different limit, what we call a ``pole on a pole''. The limiting procedure is not unique; it is sensitive to how quickly some parameters approach zero. We also show that there exists no improved coordinate transformation which would remove the negative energy density. We conclude that negative energy is an intrinsic part of this class of solutions.Comment: 13 pages, 3 figure

Biocompatible Polymer Nanoparticles for Intra-cellular Applications

Polymeric styrene microspheres have a great potential at the interface of chemistry and biology. The progress of the synthetic development of multifunctional microspheres and their use as delivery agents of different biomolecules into cells is discussed. Their multifunctional properties open a wide range of applications from intracellular real-time sensors, to the use of microspheres as catalysts performing exogenous chemistry within cells

Measuring the quantum statistics of an atom laser beam

We propose and analyse a scheme for measuring the quadrature statistics of an atom laser beam using extant optical homodyning and Raman atom laser techniques. Reversal of the normal Raman atom laser outcoupling scheme is used to map the quantum statistics of an incoupled beam to an optical probe beam. A multimode model of the spatial propagation dynamics shows that the Raman incoupler gives a clear signal of de Broglie wave quadrature squeezing for both pulsed and continuous inputs. Finally, we show that experimental realisations of the scheme may be tested with existing methods via measurements of Glauber's intensity correlation function.Comment: 4 pages, 3 figure

Editorial Introduction

This Article is a forward to nine articles from the 2001 Symposium on Natural Law and Human Fulfillment, held at Notre Dame Law School. The Symposium was held to mark the 35th anniversary of the publication of Germain Grisez\u27s The First Principle of Practical Reason: A Commentary on the Summa Theologiae

Analytical solutions to the spin-1 Bose-Einstein condensates

We analytically solve the one-dimensional coupled Gross-Pitaevskii equations which govern the motion of F=1 spinor Bose-Einstein condensates. The nonlinear density-density interactions are decoupled by making use of the unique properties of the Jacobian elliptical functions. Several types of complex stationary solutions are deduced. Furthermore, exact non-stationary solutions to the time-dependent Gross-Pitaevskii equations are constructed by making use of the spin-rotational symmetry of the Hamiltonian. The spin-polarizations exhibit kinked configurations. Our method is applicable to other coupled nonlinear systems.Comment: 12 figure

What's Decidable About Sequences?

We present a first-order theory of sequences with integer elements, Presburger arithmetic, and regular constraints, which can model significant properties of data structures such as arrays and lists. We give a decision procedure for the quantifier-free fragment, based on an encoding into the first-order theory of concatenation; the procedure has PSPACE complexity. The quantifier-free fragment of the theory of sequences can express properties such as sortedness and injectivity, as well as Boolean combinations of periodic and arithmetic facts relating the elements of the sequence and their positions (e.g., "for all even i's, the element at position i has value i+3 or 2i"). The resulting expressive power is orthogonal to that of the most expressive decidable logics for arrays. Some examples demonstrate that the fragment is also suitable to reason about sequence-manipulating programs within the standard framework of axiomatic semantics.Comment: Fixed a few lapses in the Mergesort exampl

Fingerprints of Spin-Orbital Physics in Crystalline O2_2

The alkali hyperoxide KO$_2$ is a molecular analog of strongly-correlated systems, comprising of orbitally degenerate magnetic O$_2^-$ ions. Using first-principles electronic structure calculations, we set up an effective spin-orbital model for the low-energy \textit{molecular} orbitals and argue that many anomalous properties of KO$_2$ replicate the status of its orbital system in various temperature regimes.Comment: 4 pages, 2 figures, 1 tabl