Guided atom laser : a new tool for guided atom optics

We present a guided atom laser. A Bose-Einstein condensate (BEC) is created in a crossed hybrid magnetic and an elongated optical trap, which acts as a matterwave guide. Atoms are extracted from the BEC by radio frequency (rf) outcoupling and then guided in the horizontal optical matterwave guide. This method allows to control the acceleration of the beam and to achieve large de Broglie wavelength. We also measure the longitudinal energy of the guided atom laser using atom optical elements based on a blue light barrier

Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator

<p>Abstract</p> <p>Background</p> <p>A significant reduction in parasite clearance rates following artesunate treatment of falciparum malaria, and increased failure rates following artemisinin combination treatments (ACT), signaled emergent artemisinin resistance in Western Cambodia. Accurate measurement of parasite clearance is therefore essential to assess the spread of artemisinin resistance in <it>Plasmodium falciparum</it>. The slope of the log-parasitaemia <it>versus </it>time relationship is considered to be the most robust measure of anti-malarial effect. However, an initial lag phase of numerical instability often precedes a steady exponential decline in the parasite count after the start of anti-malarial treatment. This lag complicates the clearance estimation, introduces observer subjectivity, and may influence the accuracy and consistency of reported results.</p> <p>Methods</p> <p>To address this problem, a new approach to modelling clearance of malaria parasites from parasitaemia-time profiles has been explored and validated. The methodology detects when a lag phase is present, selects the most appropriate model (linear, quadratic or cubic) to fit log-transformed parasite data, and calculates estimates of parasite clearance adjusted for this lag phase. Departing from previous approaches, parasite counts below the level of detection are accounted for and not excluded from the calculation.</p> <p>Results</p> <p>Data from large clinical studies with frequent parasite counts were examined. The effect of a lag phase on parasite clearance rate estimates is discussed, using individual patient data examples. As part of the World Wide Antimalarial Resistance Network's (WWARN) efforts to make innovative approaches available to the malaria community, an automated informatics tool: the parasite clearance estimator has been developed.</p> <p>Conclusions</p> <p>The parasite clearance estimator provides a consistent, reliable and accurate method to estimate the lag phase and malaria parasite clearance rate. It could be used to detect early signs of emerging resistance to artemisinin derivatives and other compounds which affect ring-stage clearance.</p

Photonic Band Gaps in One-Dimensionally Ordered Cold Atomic Vapors

We experimentally investigate the Bragg reflection of light at one-dimensionally ordered atomic structures by using cold atoms trapped in a laser standing wave. By a fine tuning of the periodicity, we reach the regime of multiple reflection due to the refractive index contrast between layers, yielding an unprecedented high reflectance efficiency of 80%. This result is explained by the occurrence of a photonic band gap in such systems, in accordance with previous predictions

Combating poor-quality anti-malarial medicines: a call to action

The circulation of poor-quality medicines continues to undermine the fight against many life-threatening diseases. Anti-malarial medicines appear to have been particularly compromised and present a major public health threat in malaria-endemic countries, negatively affecting individuals and their communities. Concerted collaborative efforts are required from global, regional and national organizations, involving the public and private sectors, to address the problem. While many initiatives are underway, a number of unmet needs deserve urgent and increased multisector attention. At the global level, there is a need for an international public health legal framework or treaty on poor-quality medicines, with statutes suitable for integration into national laws. In addition, increased international efforts are required to strengthen the governance of global supply chains and enhance cooperation between national medicine regulation authorities and law enforcement bodies. Increased investment is needed in innovative technologies that will enable healthcare teams to detect poor-quality medicines at all levels of the supply chain. At the regional level, a number of initiatives would be beneficial-key areas are standardization, simplification, and reciprocal recognition of registration processes and development of quality control capacity in regional centres of excellence that are better aligned with public health needs; improved surveillance methods and creation of a framework for compulsory and transparent reporting of poor-quality medicines; additional support for national medicine regulation authorities and other national partner authorities; and an increase in support for regional laboratories to boost their capabilities in detecting poor-quality medicines. It is vital that all stakeholders involved in efforts against poor-quality anti-malarial medicines extend and strengthen their actions in these critical areas and thus effectively support global health development and malaria elimination programmes

Field evaluation of two rapid diagnostic tests for Neisseria meningitidis serogroup A during the 2006 outbreak in Niger.

The Pastorex((R)) (BioRad) rapid agglutination test is one of the main rapid diagnostic tests (RDTs) for meningococcal disease currently in use in the "meningitis belt". Earlier evaluations, performed after heating and centrifugation of cerebrospinal fluid (CSF) samples, under good laboratory conditions, showed high sensitivity and specificity. However, during an epidemic, the test may be used without prior sample preparation. Recently a new, easy-to-use dipstick RDT for meningococcal disease detection on CSF was developed by the Centre de Recherche Médicale et Sanitaire in Niger and the Pasteur Institute in France. We estimate diagnostic accuracy in the field during the 2006 outbreak of Neisseria meningitidis serogroup A in Maradi, Niger, for the dipstick RDT and Pastorex((R)) on unprepared CSF, (a) by comparing each test's sensitivity and specificity with previously reported values; and (b) by comparing results for each test on paired samples, using McNemar's test. We also (c) estimate diagnostic accuracy of the dipstick RDT on diluted whole blood. We tested unprepared CSF and diluted whole blood from 126 patients with suspected meningococcal disease presenting at four health posts. (a) Pastorex((R)) sensitivity (69%; 95%CI 57-79) was significantly lower than found previously for prepared CSF samples [87% (81-91); or 88% (85-91)], as was specificity [81% (95%CI 68-91) vs 93% (90-95); or 93% (87-96)]. Sensitivity of the dipstick RDT [89% (95%CI 80-95)] was similar to previously reported values for ideal laboratory conditions [89% (84-93) and 94% (90-96)]. Specificity, at 62% (95%CI 48-75), was significantly lower than found previously [94% (92-96) and 97% (94-99)]. (b) McNemar's test for the dipstick RDT vs Pastorex((R)) was statistically significant (p<0.001). (c) The dipstick RDT did not perform satisfactorily on diluted whole blood (sensitivity 73%; specificity 57%).Sensitivity and specificity of Pastorex((R)) without prior CSF preparation were poorer than previously reported results from prepared samples; therefore we caution against using this test during an epidemic if sample preparation is not possible. For the dipstick RDT, sensitivity was similar to, while specificity was not as high as previously reported during a more stable context. Further studies are needed to evaluate its field performance, especially for different populations and other serogroups

Dealing with indeterminate outcomes in antimalarial drug efficacy trials: a comparison between complete case analysis, multiple imputation and inverse probability weighting.

BACKGROUND: Antimalarial clinical efficacy studies for uncomplicated Plasmodium falciparum malaria frequently encounter situations in which molecular genotyping is unable to discriminate between parasitic recurrence, either new infection or recrudescence. The current WHO guideline recommends excluding these individuals with indeterminate outcomes in a complete case (CC) analysis. Data from the four artemisinin-based combination (4ABC) trial was used to compare the performance of multiple imputation (MI) and inverse probability weighting (IPW) against the standard CC analysis for dealing with indeterminate recurrences. METHODS: 3369 study participants from the multicentre study (4ABC trial) with molecularly defined parasitic recurrence treated with three artemisinin-based combination therapies were used to represent a complete dataset. A set proportion of recurrent infections (10, 30 and 45%) were reclassified as missing using two mechanisms: a completely random selection (mechanism 1); missingness weakly dependent (mechanism 2a) and strongly dependent (mechanism 2b) on treatment and transmission intensity. The performance of MI, IPW and CC approaches in estimating the Kaplan-Meier (K-M) probability of parasitic recrudescence at day 28 was then compared. In addition, the maximum likelihood estimate of the cured proportion was presented for further comparison (analytical solution). Performance measures (bias, relative bias, standard error and coverage) were reported as an average from 1000 simulation runs. RESULTS: The CC analyses resulted in absolute underestimation of K-M probability of day 28 recrudescence by up to 1.7% and were associated with reduced precision and poor coverage across all the scenarios studied. Both MI and IPW method performed better (greater consistency and greater efficiency) compared to CC analysis. In the absence of censoring, the analytical solution provided the most consistent and accurate estimate of cured proportion compared to the CC analyses. CONCLUSIONS: The widely used CC approach underestimates antimalarial failure; IPW and MI procedures provided efficient and consistent estimates and should be considered when reporting the results of antimalarial clinical trials, especially in areas of high transmission, where the proportion of indeterminate outcomes could be large. The analytical solution estimating the cured proportion could provide an alternative approach, in scenarios with minimal censoring due to loss to follow-up or new infections

Implementation of a reference standard and proficiency testing programme by the World Wide Antimalarial Resistance Network (WWARN)

<p>Abstract</p> <p>Background</p> <p>The Worldwide Antimalarial Resistance Network (WWARN) is a global collaboration to support the objective that anyone affected by malaria receives effective and safe drug treatment. The Pharmacology module aims to inform optimal anti-malarial drug selection. There is an urgent need to define the drug exposure - effect relationship for most anti-malarial drugs. Few anti-malarials have had their therapeutic blood concentration levels defined. One of the main challenges in assessing safety and efficacy data in relation to drug concentrations is the comparability of data generated from different laboratories. To explain differences in anti-malarial pharmacokinetics in studies with different measurement laboratories it is necessary to confirm the accuracy of the assay methods. This requires the establishment of an external quality assurance process to assure results that can be compared. This paper describes this process.</p> <p>Methods</p> <p>The pharmacology module of WWARN has established a quality assurance/quality control (QA/QC) programme consisting of two separate components:</p> <p indent="1">1. A proficiency testing programme where blank human plasma spiked with certified reference material (CRM) in different concentrations is sent out to participating bioanalytical laboratories.</p> <p indent="1">2. A certified reference standard programme where accurately weighed amounts of certified anti-malarial reference standards, metabolites, and internal standards are sent to participating bioanalytical and in vitro laboratories.</p> <p>Conclusion</p> <p>The proficiency testing programme is designed as a cooperative effort to help participating laboratories assess their ability to carry out drug analysis, resolve any potential problem areas and to improve their results - and, in so doing, to improve the quality of anti-malarial pharmacokinetic data published and shared with WWARN.</p> <p>By utilizing the same source of standards for all laboratories, it is possible to minimize bias arising from poor quality reference standards. By providing anti-malarial drug standards from a central point, it is possible to lower the cost of these standards.</p

Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007)

BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality