Treatment of falciparum malaria in the age of drug-resistance

The growing problem of drug resistance has greatly complicated the treatment for falciparum malaria. Whereaschloroquine and sulfadoxine/ pyrimethamine could once cure most infections, this is no longer true and requiresexamination of alternative regimens. Not all treatment failures are drug resistant and other issues such asexpired antimalarials and patient compliance need to be considered. Continuation of a failing treatment policyafter drug resistance is established suppresses infections rather than curing them, leading to increasedtransmission of malaria, promotion of epidemics and loss of public confidence in malaria control programs.Antifolate drug resistance (i.e. pyrimethamine) means that new combinations are urgently needed particularlybecause addition of a single drug to an already failing regimen is rarely effective for very long. Atovaquone/proguanil and mefloquine have been used against multiple drug resistant falciparum malaria with resistance toeach having been documented soon after drug introduction. Drug combinations delay further transmission ofresistant parasites by increasing cure rates and inhibiting formation of gametocytes. Most currentlyrecommended drug combinations for falciparum malaria are variants of artemisinin combination therapy wherea rapidly acting artemisinin compound is combined with a longer half-life drug of a different class. Artemisininsused include dihydroartemisinin, artesunate, artemether and companion drugs include mefloquine, amodiaquine,sulfadoxine/ pyrimethamine, lumefantrine, piperaquine, pyronaridine, chlorproguanil/dapsone. The standard ofcare must be to cure malaria by killing the last parasite. Combination antimalarial treatment is vital not only tothe successful treatment of individual patients but also for public health control of malaria

Sum of Two Squares - Pair Correlation and Distribution in Short Intervals

In this work we show that based on a conjecture for the pair correlation of integers representable as sums of two squares, which was first suggested by Connors and Keating and reformulated here, the second moment of the distribution of the number of representable integers in short intervals is consistent with a Poissonian distribution, where "short" means of length comparable to the mean spacing between sums of two squares. In addition we present a method for producing such conjectures through calculations in prime power residue rings and describe how these conjectures, as well as the above stated result, may by generalized to other binary quadratic forms. While producing these pair correlation conjectures we arrive at a surprising result regarding Mertens' formula for primes in arithmetic progressions, and in order to test the validity of the conjectures, we present numericalz computations which support our approach.Comment: 3 figure

Reemergence of epidemic malaria in the highlands of western Kenya.

Hospital records (1990-1997) of a tea company in the Kericho district, western Kenya, showed malaria epidemics almost annually from May to July, with an annual attack rate of 50%, 857 hospitalizations per 100,000 per year, and 42 deaths per 100,000 per year; 32% of deaths in hospitalized patients were caused by malaria. A questionnaire survey (June 1997) of 244 patients hospitalized for malaria showed that only 8% had traveled to an area with known malaria transmission 30 days before diagnosis. The increasing malaria incidence may be due to drug resistance

Rapid mortality transition of Pacific Islands in the 19th century

The depopulation of Pacific islands during the 16th to 19th centuries is a striking example of historical mass mortality due to infectious disease. Pacific Island populations have not been subject to such cataclysmic infectious disease mortality since. Here we explore the processes which could have given rise to this shift in infectious disease mortality patterns. We show, using mathematical models, that the population dynamics exhibited by Pacific Island populations are unlikely to be the result of Darwinian evolution. We propose that extreme mortality during first-contact epidemics is a function of epidemiological isolation, not a lack of previous selection. If, as pathogens become established in populations, extreme mortality is rapidly suppressed by herd immunity, Pacific Island population mortality patterns can be explained with no need to invoke genetic change. We discuss the mechanisms by which this could occur, including (i) a link between the proportion of the population transmitting infectious agents and case-fatality rates, and (ii) the course of infection with pathogens such as measles and smallpox being more severe in adults than in children. Overall, we consider the present-day risk of mass mortality from newly emerging infectious diseases is unlikely to be greater on Pacific islands than in other geographical areas

Efficient solar cells by space processing

Thin films of electron beam evaporated silicon were deposited on molybdenum, tantalum, tungsten and molybdenum disilicide under ultrahigh vacuum conditions. Mass spectra from a quadrapole residual gas analyzer were used to determine the partial pressure of 13 residual gases during each processing step. Surface contamination and interdiffusion were monitored by in situ Auger electron spectrometry. The presence of phosphorus in the silicon was responsible for attaining elevated temperatures with silicide formations. Heteroepitaxial silicon growth was sensitive to the presence of oxygen during deposition, the rate and length of deposition as well as the substrate orientation

Spatial Correlation Function of X-ray Selected AGN

We present a detailed description of the first direct measurement of the spatial correlation function of X-ray selected AGN. This result is based on an X-ray flux-limited sample of 219 AGN discovered in the contiguous 80.7 deg^2 region of the ROSAT North Ecliptic Pole (NEP) Survey. Clustering is detected at the 4 sigma level at comoving scales in the interval r = 5-60 h^-1 Mpc. Fitting the data with a power law of slope gamma=1.8, we find a correlation length of r_0 = 7.4 (+1.8, -1.9) h^-1 Mpc (Omega_M=0.3, Omega_Lambda=0.7). The median redshift of the AGN contributing to the signal is z_xi=0.22. This clustering amplitude implies that X-ray selected AGN are spatially distributed in a manner similar to that of optically selected AGN. Furthermore, the ROSAT NEP determination establishes the local behavior of AGN clustering, a regime which is poorly sampled in general. Combined with high-redshift measures from optical studies, the ROSAT NEP results argue that the AGN correlation strength essentially does not evolve with redshift, at least out to z~2.2. In the local Universe, X-ray selected AGN appear to be unbiased relative to galaxies and the inferred X-ray bias parameter is near unity, b_X~1. Hence X-ray selected AGN closely trace the underlying mass distribution. The ROSAT NEP AGN catalog, presented here, features complete optical identifications and spectroscopic redshifts. The median redshift, X-ray flux, and X-ray luminosity are z=0.41, f_X=1.1*10^-13 cgs, and L_X=9.2*10^43 h_70^-2 cgs (0.5-2.0 keV), respectively. Unobscured, type 1 AGN are the dominant constituents (90%) of this soft X-ray selected sample of AGN.Comment: 17 pages, 8 figures, accepted for publication in ApJ, a version with high-resolution figures is available at http://www.eso.org/~cmullis/papers/Mullis_et_al_2004b.ps.gz, a machine-readable version of the ROSAT NEP AGN catalog is available at http://www.eso.org/~cmullis/research/nep-catalog.htm

Principal forms X^2 + nY^2 representing many integers

In 1966, Shanks and Schmid investigated the asymptotic behavior of the number of positive integers less than or equal to x which are represented by the quadratic form X^2+nY^2. Based on some numerical computations, they observed that the constant occurring in the main term appears to be the largest for n=2. In this paper, we prove that in fact this constant is unbounded as n runs through positive integers with a fixed number of prime divisors.Comment: 10 pages, title has been changed, Sections 2 and 3 are new, to appear in Abh. Math. Sem. Univ. Hambur

Quasar Clustering and the Lifetime of Quasars

Although the population of luminous quasars rises and falls over a period of 10^9 years, the typical lifetime of individual quasars is uncertain by several orders of magnitude. We show that quasar clustering measurements can substantially narrow the range of possible lifetimes with the assumption that luminous quasars reside in the most massive host halos. If quasars are long-lived, then they are rare phenomena that are highly biased with respect to the underlying dark matter, while if they are short-lived they reside in more typical halos that are less strongly clustered. For a given quasar lifetime, we calculate the minimum host halo mass by matching the observed space density of quasars, using the Press-Schechter approximation. We use the results of Mo & White to calculate the clustering of these halos, and hence of the quasars they contain, as a function of quasar lifetime. A lifetime of t_Q = 4 x 10^7 years, the e-folding timescale of an Eddington luminosity black hole with accretion efficiency eps=0.1, corresponds to a quasar correlation length r_0 ~ 10 Mpc/h in low-density cosmological models at z=2-3; this value is consistent with current clustering measurements, but these have large uncertainties. High-precision clustering measurements from the 2dF and Sloan quasar surveys will test our key assumption of a tight correlation between quasar luminosity and host halo mass, and if this assumption holds then they should determine t_Q to a factor of three or better. An accurate determination of the quasar lifetime will show whether supermassive black holes acquire most of their mass during high-luminosity accretion, and it will show whether the black holes in the nuclei of typical nearby galaxies were once the central engines of high-luminosity quasars.Comment: ApJ Accepted (Feb 2001). 30 pages, 8 embedded ps figures, AASTEX5. Added discussion of quasar luminosity evolution. Also available at http://www.ociw.edu/~martini/pubs

Discovery of a Clustered Quasar Pair at z ~ 5: Biased Peaks in Early Structure Formation

We report a discovery of a quasar at z = 4.96 +- 0.03 within a few Mpc of the quasar SDSS 0338+0021 at z = 5.02 +- 0.02. The newly found quasar has the SDSS i and z magnitudes of ~ 21.2, and an estimated absolute magnitude M_B ~ -25.2. The projected separation on the sky is 196 arcsec, and the redshift difference Delta z = 0.063 +- 0.008. The probability of finding this quasar pair by chance in the absence of clustering in this particular volume is ~ 10^-4 to 10^-3. We conclude that the two objects probably mark a large-scale structure, possibly a protocluster, at z ~ 5. This is the most distant such structure currently known. Our search in the field of 13 other QSOs at z >~ 4.8 so far has not resulted in any detections of comparable luminous QSO pairs, and it is thus not yet clear how representative is this structure at z ~ 5. However, along with the other evidence for clustering of quasars and young galaxies at somewhat lower redshifts, the observations are at least qualitatively consistent with a strong biasing of the first luminous and massive objects, in agreement with general predictions of theoretical models. More extensive searches for clustered quasars and luminous galaxies at these redshifts will provide valuable empirical constraints for our understanding of early galaxy and structure formation.Comment: Latex file, 8 pages, 3 eps figures, sty files included. To appear in the Ap

Generative mechanisms for innovation in information infrastructures

This paper investigates how innovation of ICT based services takes place within existing infrastructures, including the whole network of technology, vendors and customers. Our research question is, how can an information infrastructure provide generative mechanisms for innovation of ICT based services? Building on a critical realist approach, our empirical evidence was a case study within an international airline, aiming to diversify its services. From our analysis we propose that there are two self-reinforcement mechanisms in information infrastructures. First, we identified the innovation reinforcement mechanism, resulting in new services. Second, there is the service reinforcement mechanism, resulting in more users and profits. The practical implication of our framework is to show that although ICT-based innovation cannot be planned and managed in detail, the innovation mechanism may help organisations to facilitate the innovation process in a structured way