Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison.

BACKGROUND: Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefloquine is widely recommended in southeast Asia, but its high cost and tolerability profile remain obstacles to widespread deployment. To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefloquine, we compared the safety, tolerability, efficacy, and effectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar (Burma). METHODS: We did an open randomised comparison of 3-day regimens of artesunate-mefloquine (12/25 mg/kg) versus dihydroartemisinin-piperaquine (6.3/50 mg/kg) for the treatment of children aged 1 year or older and in adults with uncomplicated falciparum malaria in Rakhine State, western Myanmar. Within each group, patients were randomly assigned supervised or non-supervised treatment. The primary endpoint was the PCR-confirmed parasitological failure rate by day 42. Failure rates at day 42 were estimated by Kaplan-Meier survival analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN27914471. FINDINGS: Of 652 patients enrolled, 327 were assigned dihydroartemisinin-piperaquine (156 supervised and 171 not supervised), and 325 artesunate-mefloquine (162 and 163, respectively). 16 patients were lost to follow-up, and one patient died 22 days after receiving dihydroartemisinin-piperaquine. Recrudescent parasitaemias were confirmed in only two patients; the day 42 failure rate was 0.6% (95% CI 0.2-2.5) for dihydroartemisinin-piperaquine and 0 (0-1.2) for artesunate-mefloquine. Whole-blood piperaquine concentrations at day 7 were similar for patients with observed and non-observed dihydroartemisinin-piperaquine treatment. Gametocytaemia developed more frequently in patients who had received dihydroartemisinin-piperaquine than in those on artesunate-mefloquine: day 7, 18 (10%) of 188 versus five (2%) of 218; relative risk 4.2 (1.6-11.0) p=0.011. INTERPRETATION: Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups. The effectiveness of the unsupervised treatment, as in the usual context of use, equalled its supervised efficacy, indicating good adherence without supervision. Dihydroartemisinin-piperaquine is a good alternative to artesunate-mefloquine

Differences in decision-making behavior between elite and amateur team-handball players in a near-game test situation

Athletic features distinguishing experts from non-experts in team sports are relevant for performance analyses, talent identification and successful training. In this respect, perceptual-cognitive factors like decision making have been proposed to be important predictor of talent but, however, assessing decision making in team sports remains a challenging endeavor. In particular, it is now known that decisions expressed by verbal reports or micro-movements in the laboratory differ from those actually made in on-field situations in play. To address this point, our study compared elite and amateur players' decision-making behavior in a near-game test environment including sport-specific sensorimotor responses. Team-handball players (N = 44) were asked to respond as quickly as possible to representative, temporally occluded attack sequences in a team-handball specific defense environment on a contact plate system. Specifically, participants had to choose and perform the most appropriate out of four prespecified, defense response actions. The frequency of responses and decision time were used as dependent variables representing decision-making behavior. We found that elite players responded significantly more often with offensive responses (p < 0.05, odds ratios: 2.76-3.00) in left-handed attack sequences. Decision time decreased with increasing visual information, but no expertise effect was found. We suppose that expertise-related knowledge and processing of kinematic information led to distinct decision-making behavior between elite and amateur players, evoked in a domain-specific and near-game test setting. Results also indicate that the quality of a decision might be of higher relevance than the required time to decide. Findings illustrate application opportunities in the context of performance analyses and talent identification processes

Observations of Mkn 421 in 2004 with H.E.S.S. at large zenith angles

Mkn 421 was observed during a high flux state for nine nights in April and May 2004 with the fully operational High Energy Stereoscopic System (H.E.S.S.) in Namibia. The observations were carried out at zenith angles of 60$^\circ$--65$^\circ$, which result in an average energy threshold of 1.5 TeV and a collection area reaching 2~km$^2$ at 10~TeV. Roughly 7000 photons from Mkn~421 were accumulated with an average gamma-ray rate of 8 photons/min. The overall significance of the detection exceeds 100 standard deviations. The light-curve of integrated fluxes above 2~TeV shows changes of the diurnal flux up to a factor of 4.3. For nights of high flux, intra-night variability is detected with a decay time of less than 1 hour. The time averaged energy spectrum is curved and is well described by a power-law with a photon index \egamm and an exponential cutoff at \ecut~TeV and an average integral flux above 2~TeV of 3 Crab flux units. Significant variations of the spectral shape are detected with a spectral hardening as the flux increases. Contemporaneous multi-wavelength observations at lower energies (X-rays and gamma-rays above $\approx 300$~GeV) indicate smaller relative variability amplitudes than seen above 2~TeV during high flux state observed in April 2004.Comment: 5 pages, 4 figures, published in A&

Very high energy gamma rays from the direction of Sagittarius A*.

We report the detection of a point-like source of very high energy (VHE) -rays coincident within 1' of Sgr A *, obtained with the HESS array of Cherenkov telescopes. The -rays exhibit a power-law energy spectrum with a spectral index of and a flux above the 165 GeV threshold of m -2 s -1. The measured flux and spectrum differ substantially from recent results reported in particular by the CANGAROO collaboration

Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S

We report the discovery of very-high-energy (VHE) gamma-ray emission of the binary system PSR B1259-63/SS 2883 of a radio pulsar orbiting a massive, luminous Be star in a highly eccentric orbit. The observations around the 2004 periastron passage of the pulsar were performed with the four 13 m Cherenkov telescopes of the H.E.S.S. experiment, recently installed in Namibia and in full operation since December 2003. Between February and June 2004, a gamma-ray signal from the binary system was detected with a total significance above 13 sigma. The flux was found to vary significantly on timescales of days which makes PSR B1259-63 the first variable galactic source of VHE gamma-rays observed so far. Strong emission signals were observed in pre- and post-periastron phases with a flux minimum around periastron, followed by a gradual flux decrease in the months after. The measured time-averaged energy spectrum above a mean threshold energy of 380 GeV can be fitted by a simple power law F_0(E/1 TeV)^-Gamma with a photon index Gamma = 2.7+-0.2_stat+-0.2_sys and flux normalisation F_0 = (1.3+-0.1_stat+-0.3_sys) 10^-12 TeV^-1 cm^-2 s^-1. This detection of VHE gamma-rays provides unambiguous evidence for particle acceleration to multi-TeV energies in the binary system. In combination with coeval observations of the X-ray synchrotron emission by the RXTE and INTEGRAL instruments, and assuming the VHE gamma-ray emission to be produced by the inverse Compton mechanism, the magnetic field strength can be directly estimated to be of the order of 1 G.Comment: 10 pages, 8 figures, accepted in Astronomy and Astrophysics on 2 June 2005, replace: document unchanged, replaced author field in astro-ph entry - authors are all members of the H.E.S.S. collaboration and three additional authors (99+3, see document

Mapping cropland fallow areas in Myanmar to scale up sustainable intensification of pulse crops in the farming system

Cropland fallows are the next best-bet for intensification and extensification, leading to increased food production and adding to the nutritional basket. The agronomical suitability of these lands can decide the extent of usage of these lands. Myanmar’s agricultural land (over 13.8 Mha) has the potential to expand by another 50% into additional fallow areas. These areas may be used to grow short-duration pulses, which are economically important and nutritionally rich, and constitute the diets of millions of people as well as provide an important source of livestock feed throughout Asia. Intensifying rice fallows will not only improve the productivity of the land but also increase the income of the smallholder farmers. The enhanced cultivation of pulses will help improve nutritional security in Myanmar and also help conserve natural resources and reduce environmental degradation. The objectives of this study was to use remote sensing methods to identify croplands in Myanmar and cropland fallow areas in two important agro-ecological regions, delta and coastal region and the dry zone. The study used moderate-resolution imaging spectroradiometer (MODIS) 250-m, 16-day normalized difference vegetation index (NDVI) maximum value composite (MVC), and land surface water index (LSWI) for one 1 year (1 June 2012–31 May 2013) along with seasonal field-plot level information and spectral matching techniques to derive croplands versus cropland fallows for each of the three seasons: the monsoon period between June and October; winter period between November and February; and summer period between March and May. The study showed that Myanmar had total net cropland area (TNCA) of 13.8 Mha. Cropland fallows during the monsoon season account for a meagre 2.4% of TNCA. However, in the winter season, 56.5% of TNCA (or 7.8 Mha) were classified as cropland fallows and during the summer season, 82.7% of TNCA (11.4 Mha) were cropland fallows. The producer’s accuracy of the cropland fallow class varied between 92 and 98% (errors of omission of 2 to 8%) and user’s accuracy varied between 82 and 92% (errors of commission of 8 to 18%) for winter and summer, respectively. Overall, the study estimated 19.2 Mha cropland fallows from the two major seasons (winter and summer). Out of this, 10.08 Mha has sufficient moisture (either from rainfall or stored soil water content) to grow short-season pulse crops. This potential with an estimated income of US$300 per hectare, if exploited sustainably, is estimated to bring an additional net income of about US$ 1.5 billion to Myanmar per year if at least half (5.04 Mha) of the total cropland fallows (10.08 Mha) is covered with short season pulses

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B

BACKGROUND: After perinatal transmission of hepatitis B virus, infants of anti-HBe positive HBsAg carrier mothers may develop fulminant hepatitis B. Previously it has been suggested, that fulminant hepatitis B in adults was associated with specific mutations in the HBV-genome. The aim of this study was to investigate, whether specific viral variants are associated with fulminant hepatitis B in young infants. METHODS: The complete HBV-genomes of five mothers and their infants with fulminant hepatitis were isolated from the sera, amplified and directly sequenced. RESULTS: Between 6 and 43 base pair exchanges between the HBV genomes of the infants and their mothers were identified. The mutations spread over the entire virus genome. Nucleotide exchanges in the basic core promotor and precore region were identified in all cases. A heterogeneous virus population was detected in four mothers. CONCLUSIONS: Many new mutations were proved to emerge during fulminant hepatitis B in infants, who had been perinatally infected. HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers. The data suggest that the selection of a specific HBeAg negative viral strain may be associated with the development of fulminant hepatitis B in children