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Sample records for baseline anti-malarial treatment

  1. Molecular markers of anti-malarial drug resistance in Lahj Governorate, Yemen: baseline data and implications

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    Chance Michael L

    2011-08-01

    Full Text Available Abstract Background This is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (CQ against falciparum malaria in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at assessment of therapeutic response to CQ and elucidation of baseline information on molecular markers for Plasmodium falciparum resistance against CQ and sulphadoxine/pyrimethamine (SP. Methods Between 2002 and 2003 the field test was conducted according to the standard WHO protocol to evaluate the therapeutic efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj Governorate in Yemen. Blood samples collected during this study were analysed for P. falciparum chloroquine resistance transporter gene (pfcrt-76 polymorphisms, mutation pfcrt-S163R and the antifolate resistance-associated mutations dihydrofolate reductase (dhfr-C59R and dihydropteroate synthase (dhps-K540E. Direct DNA sequencing of the pfcrt gene from three representative field samples was carried out after DNA amplification of the 13 exons of the pfcrt gene. Results Treatment failure was detected in 61% of the 122 cases that completed the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9. The prevalence of dhfr Arg-59 mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni CQ resistant P. falciparum carry the old world (Asian and African CQ resistant haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. Conclusion This is the first study to report baseline information on the characteristics and implications of anti-malarial drug resistance markers in Yemen. It is also the first report of the haplotype associated with CQR P. falciparum

  2. Compliance with a three-day course of artesunate-mefloquine combination and baseline anti-malarial treatment in an area of Thailand with highly multidrug resistant falciparum malaria

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    Na-Bangchang Kesara

    2010-02-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is presently recommended by the World Health Organization as first-line treatment for uncomplicated Plasmodium falciparum malaria in several countries, as a mean of prolonging the effectiveness of first-line malaria treatment regimens. A three-day course of artesunate-mefloquine (4 mg/kg body weight once daily for three consecutive days, plus 15 and 10 mg/kg body weight mefloquine on the first and second days has been adopted by Malaria Control Programme of Thailand as first-line treatment for uncomplicated falciparum malaria all over the country since 2008. The gametocytocydal anti-malarial drug primaquine is administered at the dose of 30 mg (0.6 mg/kg on the last day. The aim of the present study was to assess patient compliance of this combination regimen when applied to field condition. Methods A total of 240 patients (196 males and 44 females who were attending the malaria clinics in Mae-Sot, Tak Province and presenting with symptomatic acute uncomplicated falciparum malaria, with no reappearance of Plasmodium vivax parasitaemia during follow-up were included into the study. The first dose of the treatment was given to the patients under direct supervision. All patients were given the medication for self-treatment at home and were requested to come back for follow-up on day 3 of the initial treatment. Baseline (day 0 and day 3 whole blood mefloquine and plasma primaquine concentrations were determined by high performance liquid chromatography. Results Two patients had recrudescence on days 28 and 35. The Kaplan-Meier estimate of the 42-day efficacy rate of this combination regimen was 99.2% (238/240. Based on whole blood mefloquine and plasma primaquine concentrations on day 3 of the initial treatment, compliance with mefloquine and primaquine in this three-day artesunate-mefloquine combination regimen were 96.3% (207/215, and 98.5% (197/200, respectively. Baseline mefloquine

  3. Saleability of anti-malarials in private drug shops in Muheza, Tanzania: a baseline study in an era of assumed artemisinin combination therapy (ACT

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    Ringsted Frank M

    2011-08-01

    Full Text Available Abstract Background Artemether-lumefantrine (ALu replaced sulphadoxine-pymimethamine (SP as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant women depend on SP for Intermittent Preventive Treatment (IPTp during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform a baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. Methods All drug shops selling prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. Results All surveyed drug shops illicitly sold SP and quinine (QN, and legally amodiaquine (AQ. Calculated monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local brands of SP accounted for 74% of sales volume, compared to AQ (13%, QN (11% and ACT (2%. Conclusions In community practice, the saleability of ACT was negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated in the national anti-malarial policy. It is a major reason for concern that such drug-pressure in the community equals de facto intermittent presumptive treatment. In an area where SP drug resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp

  4. A retrospective analysis of the change in anti-malarial treatment policy: Peru

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    Vincent-Mark Arlene

    2009-04-01

    Full Text Available Abstract Background National malaria control programmes must deal with the complex process of changing national malaria treatment guidelines, often without guidance on the process of change. Selecting a replacement drug is only one issue in this process. There is a paucity of literature describing successful malaria treatment policy changes to help guide control programs through this process. Objectives To understand the wider context in which national malaria treatment guidelines were formulated in a specific country (Peru. Methods Using qualitative methods (individual and focus group interviews, stakeholder analysis and a review of documents, a retrospective analysis of the process of change in Peru's anti-malarial treatment policy from the early 1990's to 2003 was completed. Results The decision to change Peru's policies resulted from increasing levels of anti-malarial drug resistance, as well as complaints from providers that the drugs were no longer working. The context of the change occurred in a time in which Peru was changing national governments, which created extreme challenges in moving the change process forward. Peru utilized a number of key strategies successfully to ensure that policy change would occur. This included a having the process directed by a group who shared a common interest in malaria and who had long-established social and professional networks among themselves, b engaging in collaborative teamwork among nationals and between nationals and international collaborators, c respect for and inclusion of district-level staff in all phases of the process, d reliance on high levels of technical and scientific knowledge, e use of standardized protocols to collect data, and f transparency. Conclusion Although not perfectly or fully implemented by 2003, the change in malaria treatment policy in Peru occurred very quickly, as compared to other countries. They identified a problem, collected the data necessary to justify the

  5. Co-treatment with the anti-malarial drugs mefloquine and primaquine highly sensitizes drug-resistant cancer cells by increasing P-gp inhibition.

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    Kim, Ju-Hwa; Choi, Ae-Ran; Kim, Yong Kee; Yoon, Sungpil

    2013-11-22

    The purpose of this study was to identify conditions that will increase the sensitivity of resistant cancer cells to anti-mitotic drugs. Currently, atovaquine (ATO), chloroquine (CHL), primaquine (PRI), mefloquine (MEF), artesunate (ART), and doxycycline (DOY) are the most commonly used anti-malarial drugs. Herein, we tested whether anti-malarial drugs can sensitize drug-resistant KBV20C cancer cells. None of the six tested anti-malarial drugs was found to better sensitize the drug-resistant cells compared to the sensitive KB cells. With an exception of DOY, all other anti-malarial drugs tested could sensitize both KB and KBV20C cells to a similar extent, suggesting that anti-malarial drugs could be used for sensitive as well as resistant cancer cells. Furthermore, we examined the effects of anti-malarial drugs in combination with an antimitotic drug, vinblastine (VIN) on the sensitisation of resistant KBV20C cells. Using viability assay, microscopic observation, assessment of cleaved PARP, and Hoechst staining, we identified that two anti-malarial drugs, PRI and MEF, highly sensitized KBV20C-resistant cells to VIN treatment. Moreover, PRI- or MEF-induced sensitisation was not observed in VIN-treated sensitive KB parent cells, suggesting that the observed effect is specific to resistant cancer cells. We demonstrated that the PRI and MEF sensitisation mechanism mainly depends on the inhibition of p-glycoprotein (P-gp). Our findings may contribute to the development of anti-malarial drug-based combination therapies for patients resistant to anti-mitotic drugs.

  6. Multiple treatment comparisons in a series of anti-malarial trials with an ordinal primary outcome and repeated treatment evaluations

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    Youdom Solange

    2012-05-01

    Full Text Available Abstract Background Artemisinin-based combination therapies (ACT are widely used in African countries, including Cameroon. Between 2005 and 2007, five randomized studies comparing different treatment arms among artesunate-amodiaquine and other ACT were conducted in Cameroonian children aged two to 60 months who had uncomplicated Plasmodium falciparum malaria. In these studies, the categorical criterion proposed by the World Health Organization (WHO to assess the relative effectiveness of anti-malarial drugs was repeatedly evaluated on Days 14, 21 and 28 after treatment initiation. The aim of the present study was to compare the effects of different treatments on this repeated ordinal outcome, hence using the fully available information. Methods The quantitative synthesis was based on individual patient data. Due to the incomplete block design concerning treatment arms between different trials, a mixed treatment comparison (MTC meta-analysis approach was adopted. The repeated ordinal outcome was modelled through a latent variable, as a proportional odds mixed model with trial, period and treatment arms as covariates. The model was further complexified to account for the variance heterogeneity, and the individual log-residual variance was modelled as a linear mixed model, as well. The effects of individual covariates at inclusion, such as parasitaemia, fever, gender and weight, were also tested. Model parameters were estimated using a Bayesian approach via the WinBUGS software. After selecting the best model using Deviance Information Criterion (DIC, mixed treatment comparisons were based on the estimated treatment effects. Results Modeling the residual variance improved the model ability to adjust the data. The results showed that, compared to artesunate-amodiaquine (ASAQ, dihydroartemisinin-piperaquine (DHPP was significantly more efficacious. Artesunate-chlorproguanil-dapsone (ASCD was less efficacious than artesunate

  7. Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

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    Avinaba Mukherjee

    2016-03-01

    Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

  8. High prevalence of pfdhfr-pfdhps triple mutations associated with anti-malarial drugs resistance in Plasmodium falciparum isolates seven years after the adoption of sulfadoxine-pyrimethamine in combination with artesunate as first-line treatment in Iran.

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    Rouhani, Maryam; Zakeri, Sedigheh; Pirahmadi, Sakineh; Raeisi, Ahmad; Djadid, Navid Dinparast

    2015-04-01

    The spread of anti-malarial drug resistance will challenge any malaria control and elimination strategies, and routine monitoring of resistance-associated molecular markers of commonly used anti-malarial drugs is very important. Therefore, in the present investigation, the extent of mutations/haplotypes in dhfr and dhps genes of Plasmodium falciparum isolates (n=72) was analyzed seven years after the introduction of sulfadoxine-pyrimethamine (SP) plus artesunate (AS) as first-line anti-malarial treatment in Iran using PCR-RFLP methods. The results showed that the majority of the patients (97.2%) carried both 59R and 108N mutations in pure form with wild-type genotype at positions N51 and I164. Additionally, a significant increase (Pdrug for treatment of falciparum patients in these malaria-endemic areas of Iran. However, no quintuple mutations associated with treatment failure were detected. In conclusion, the present results along with in vivo assays suggest that seven years after the adoption of SP-AS as the first-line treatment in Iran, this drug remains efficacious for treatment of uncomplicated falciparum malaria, as a partner drug with AS in these malaria-endemic areas.

  9. Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity

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    Rijpma, S.R.; Heuvel, J.J.; Velden, M. van der; Sauerwein, R.W.; Russel, F.G.; Koenderink, J.B.

    2014-01-01

    BACKGROUND: Therapeutic blood plasma concentrations of anti-malarial drugs are essential for successful treatment. Pharmacokinetics of pharmaceutical compounds are dependent of adsorption, distribution, metabolism, and excretion. ATP binding cassette (ABC) transport proteins are particularly involve

  10. Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi from Ghana and Gabon

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    Kreuels Benno

    2008-10-01

    Full Text Available Abstract Background Intermittent preventive treatment in infants (IPTi with sulphadoxine-pyrimethamine (SP reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials. Methods Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests. Results Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort. Conclusion The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low. Trial registration Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial and NCT ID # 00167843 (Lambaréné Trial, http://www.clinicaltrials.gov.

  11. Review of pyronaridine anti-malarial properties and product characteristics

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    Croft Simon L

    2012-08-01

    Full Text Available Abstract Pyronaridine was synthesized in 1970 at the Institute of Chinese Parasitic Disease and has been used in China for over 30 years for the treatment of malaria. Pyronaridine has high potency against Plasmodium falciparum, including chloroquine-resistant strains. Studies in various animal models have shown pyronaridine to be effective against strains resistant to other anti-malarials, including chloroquine. Resistance to pyronaridine appears to emerge slowly and is further retarded when pyronaridine is used in combination with other anti-malarials, in particular, artesunate. Pyronaridine toxicity is generally less than that of chloroquine, though evidence of embryotoxicity in rodents suggests use with caution in pregnancy. Clinical pharmacokinetic data for pyronaridine indicates an elimination T1/2 of 13.2 and 9.6 days, respectively, in adults and children with acute uncomplicated falciparum and vivax malaria in artemisinin-combination therapy. Clinical data for mono or combined pyronaridine therapy show excellent anti-malarial effects against P. falciparum and studies of combination therapy also show promise against Plasmodium vivax. Pyronaridine has been developed as a fixed dose combination therapy, in a 3:1 ratio, with artesunate for the treatment of acute uncomplicated P. falciparum malaria and blood stage P. vivax malaria with the name of Pyramax® and has received Positive Opinion by European Medicines Agency under the Article 58 procedure.

  12. Does anti-malarial drug knowledge predict anti-malarial dispensing practice in drug outlets? A survey of medicine retailers in western Kenya

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    Rusk Andria

    2012-08-01

    Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial. Methods To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of the Webuye Health and Demographic Surveillance Site in the Bungoma East District of western Kenya. Results Most of the medicine retailers surveyed (65% were able to identify artemether-lumefantrine (AL as the Kenyan Ministry of Health recommended first-line anti-malarial therapy for uncomplicated malaria. Retailers who correctly identified this treatment were also more likely to recommend AL to adult and paediatric customers. However, the proportion of medicine retailers who recommend the correct treatment is disappointingly low. Only 48% would recommend AL to adults, and 37% would recommend it to children. It was discovered that customer demand has an influence on retailer behaviour. Retailer training and education were found to be correlated with anti-malarial drug knowledge, which in turn is correlated with dispensing practices. Medicine retailer behaviour, including patient referral practice and dispensing practices, are also correlated with knowledge of the first-line anti-malarial medication. The Kenya Ministry of Health guidelines were found to influence retailer drug stocking and dispensing behaviours. Conclusion Most medicine retailers could identify the recommended first-line treatment for uncomplicated malaria, but the percentage that could

  13. Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys

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    Littrell Megan

    2011-10-01

    Full Text Available Abstract Background Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT. The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Methods Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Results Most public outlets (85% and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%, drug stores (14%, mobile providers (4% and grocery stores (2%. Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61% and private (42% sectors. Conclusions While data on the anti-malarial

  14. Access to artesunate-amodiaquine, quinine and other anti-malarials: policy and markets in Burundi

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    Dismas Baza

    2011-02-01

    Full Text Available Abstract Background Malaria is the leading cause of morbidity and mortality in post-conflict Burundi. To counter the increasing challenge of anti-malarial drug resistance and improve highly effective treatment Burundi adopted artesunate-amodiaquine (AS-AQ as first-line treatment for uncomplicated Plasmodium falciparum malaria and oral quinine as second-line treatment in its national treatment policy in 2003. Uptake of this policy in the public, private and non-governmental (NGO retail market sectors of Burundi is relatively unknown. This study was conducted to evaluate access to national policy recommended anti-malarials. Methods Adapting a standardized methodology developed by Health Action International/World Health Organization (HAI/WHO, a cross-sectional survey of 70 (24 public, 36 private, and 10 NGO medicine outlets was conducted in three regions of Burundi, representing different levels of transmission of malaria. The availability on day of the survey, the median prices, and affordability (in terms of number of days' wages to purchase treatment of AS-AQ, quinine and other anti-malarials were calculated. Results Anti-malarials were stocked in all outlets surveyed. AS-AQ was available in 87.5%, 33.3%, and 90% of public, private, and NGO retail outlets, respectively. Quinine was the most common anti-malarial found in all outlet types. Non-policy recommended anti-malarials were mainly found in the private outlets (38.9% compared to public (4.2% and NGO (0% outlets. The median price of a course of AS-AQ was US$0.16 (200 Burundi Francs, FBu for the public and NGO markets, and 3.5-fold higher in the private sector (US$0.56 or 700 FBu. Quinine tablets were similarly priced in the public (US$1.53 or 1,892.50 FBu, private and NGO sectors (both US$1.61 or 2,000 FBu. Non-policy anti-malarials were priced 50-fold higher than the price of AS-AQ in the public sector. A course of AS-AQ was affordable at 0.4 of a day's wage in the public and NGO sectors

  15. In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

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    Eberlin Marcos N

    2011-05-01

    Full Text Available Abstract Background To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Methods Crude extract (CE was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7 and -resistant (S20 strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. Results At non-toxic concentrations, the 100% ethanolic (F4 and 50% methanolic (F5 fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. Conclusions The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.

  16. The ACTwatch project: methods to describe anti-malarial markets in seven countries

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    Chapman Steven

    2011-10-01

    Full Text Available Abstract Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT and malaria diagnostics including rapid diagnostic tests (RDTs. To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the

  17. Recent progress in the development of anti-malarial quinolones.

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    Beteck, Richard M; Smit, Frans J; Haynes, Richard K; N'Da, David D

    2014-08-30

    Available anti-malarial tools have over the ten-year period prior to 2012 dramatically reduced the number of fatalities due to malaria from one million to less than six-hundred and thirty thousand. Although fewer people now die from malaria, emerging resistance to the first-line anti-malarial drugs, namely artemisinins in combination with quinolines and arylmethanols, necessitates the urgent development of new anti-malarial drugs to curb the disease. The quinolones are a promising class of compounds, with some demonstrating potent in vitro activity against the malaria parasite. This review summarizes the progress made in the development of potential anti-malarial quinolones since 2008. The efficacy of these compounds against both asexual blood stages and other stages of the malaria parasite, the nature of putative targets, and a comparison of these properties with anti-malarial drugs currently in clinical use, are discussed.

  18. Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance

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    Lee Sue J

    2009-11-01

    Full Text Available Abstract Background Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results. Methods The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. Results Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. Conclusion Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women. Patients with

  19. Epidemiological models for the spread of anti-malarial resistance

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    Antia R

    2003-02-01

    Full Text Available Abstract Background The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance. Methods We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance. Results In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population. Conclusions The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.

  20. Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu

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    Rogers William O

    2010-04-01

    Full Text Available Abstract Background Chloroquine-resistant Plasmodium falciparum was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated P. falciparum infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for Plasmodium vivax. Methods In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for P. vivax and chloroquine/sulphadoxine-pyrimethamine for P. falciparum infections. Results The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between P. falciparum and P. vivax. Twenty percent and 23% of participants with patent P. vivax and P. falciparum parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with P. vivax predominating. Among individuals participating in the clinical trial, the 28-day chloroquine P. vivax cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine P. falciparum cure rate was 97%. The single treatment failure, confirmed by merozoite surface protein-2 genotyping, was classified as a day 28 late parasitological treatment failure. All P. falciparum isolates carried the Thr-76 pfcrt mutant allele and the double Asn-108 + Arg-59 dhfr mutant alleles. Dhps mutant alleles were not detected in the study sample. Conclusion Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study

  1. Access to Artemisinin-Combination Therapy (ACT) and other Anti-Malarials: National Policy and Markets in Sierra Leone

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    Amuasi, John H.; Diap, Graciela; Nguah, Samuel Blay; Karikari, Patrick; Boakye, Isaac; Jambai, Amara; Lahai, Wani Kumba; Louie, Karly S.; Kiechel, Jean-Rene

    2012-01-01

    Malaria remains the leading burden of disease in post-conflict Sierra Leone. To overcome the challenge of anti-malarial drug resistance and improve effective treatment, Sierra Leone adopted artemisinin-combination therapy artesunate-amodiaquine (AS+AQ) as first-line treatment for uncomplicated P. falciparum malaria. Other national policy anti-malarials include artemether-lumefantrine (AL) as an alternative to AS+AQ, quinine and artemether for treatment of complicated malaria; and sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment (IPTp). This study was conducted to evaluate access to national policy recommended anti-malarials. A cross-sectional survey of 127 medicine outlets (public, private and NGO) was conducted in urban and rural areas. The availability on the day of the survey, median prices, and affordability policy and available non-policy anti-malarials were calculated. Anti-malarials were stocked in 79% of all outlets surveyed. AS+AQ was widely available in public medicine outlets; AL was only available in the private and NGO sectors. Quinine was available in nearly two-thirds of public and NGO outlets and over one-third of private outlets. SP was widely available in all outlets. Non-policy anti-malarials were predominantly available in the private outlets. AS+AQ in the public sector was widely offered for free. Among the anti-malarials sold at a cost, the same median price of a course of AS+AQ (US$1.56), quinine tablets (US$0.63), were found in both the public and private sectors. Quinine injection had a median cost of US$0.31 in the public sector and US$0.47 in the private sector, while SP had a median cost of US$0.31 in the public sector compared to US$ 0.63 in the private sector. Non-policy anti-malarials were more affordable than first-line AS+AQ in all sectors. A course of AS+AQ was affordable at nearly two days’ worth of wages in both the public and private sectors. PMID:23133522

  2. Therapeutic efficacy of artesunate in the treatment of uncomplicated Plasmodium falciparum malaria and anti-malarial, drug-resistance marker polymorphisms in populations near the China-Myanmar border

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    Huang Fang

    2012-08-01

    Full Text Available Abstract Background The aim of this study was to evaluate the clinical outcome after seven-day artesunate monotherapy for uncomplicated Plasmodium falciparum malaria in Yingjiang County along the China-Myanmar border and investigate genetic polymorphisms in the P. falciparum chloroquine-resistance transporter (pfcrt, multidrug resistance 1 (pfmdr1, dihydrofolate reductase (pfdhfr, dihydropteroate synthase (pfdhps and ATPase (pfatp6 genes. Methods Patients ≥ one year of age with fever (axillary temperature ≥37.5°C or history of fever and P. falciparum mono-infection were included. Patients received anti-malarial treatment with artesunate (total dose of 16 mg/kg over seven days by directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed based on clinical and parasitological outcomes. Treatment failure was defined as recrudescence of the original parasite and distinguished with new infection confirmed by PCR. Analysis of gene mutation and amplification were performed by nested polymerase chain reaction. Results Sixty-five patients were enrolled; 10 withdrew from the study, and six were lost to follow-up. All but two patients demonstrated adequate clinical and parasitological response; 12 had detectable parasitaemia on day 3. These two patients were confirmed to be new infection by PCR. The efficacy of artesunate was 95.9%. The pfcrt mutation in codon 76 was found in all isolates (100%, and mutations in codons 71 and 72 were found in 4.8% of parasite isolates. No mutation of pfmdr1 (codons 86 or 1246 was found. Among all samples, 5.1% were wild type for pfdhfr, whereas the other samples had mutations in four codons (51, 59, 108 and 164, and mutations in pfdhps (codons 436, 437, 540 and 581 were found in all isolates. No samples had mutations in pfatp6 codons 623 or 769, but two new mutations (N683K and R756K were found in 4.6% and 9.2% of parasite isolates, respectively. Conclusion Plasmodium

  3. Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS) pilot study

    Science.gov (United States)

    2012-01-01

    Background Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Methods Four intervention districts were purposefully selected to receive branded subsidized medicines - “ACT with a leaf”, while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention’s impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. Results At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, “ACT with a leaf” accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4) at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p<0.0001) at evaluation. Children less than five years of age had “ACT with a leaf” purchased for them more often than those

  4. Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS pilot study

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    Talisuna Ambrose O

    2012-10-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT, the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Methods Four intervention districts were purposefully selected to receive branded subsidized medicines - “ACT with a leaf”, while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention’s impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. Results At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, “ACT with a leaf” accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2% at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%. The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4 at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p Conclusions These data demonstrate that a supply-side subsidy and an intensive communications campaign

  5. Fake anti-malarials: start with the facts.

    Science.gov (United States)

    Kaur, Harparkash; Clarke, Siȃn; Lalani, Mirza; Phanouvong, Souly; Guérin, Philippe; McLoughlin, Andrew; Wilson, Benjamin K; Deats, Michael; Plançon, Aline; Hopkins, Heidi; Miranda, Debora; Schellenberg, David

    2016-02-13

    This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting.

  6. Molecular Farming in Artemisia annua, a sustainable approach to improve anti-malarial drug production

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    Giuseppe ePulice

    2016-03-01

    Full Text Available Malaria is a parasite infection affecting millions of people worldwide. Even though progresses in prevention and treatment have been developed, 198 million cases of malaria occurred in 2013, resulting in 584000 estimated deaths. 90% of all malaria deaths occurred in Africa, mostly among children under the age of five. This article aims to review malaria’s history, epidemiology and current treatments, with a particular focus on the potential of molecular farming that use metabolic engineering in plants as effective anti-malarial solution. Malaria indeed represents an example of how a health problem on one hand, may eventually influence the proper development of a country due to the burden of the disease, and on the other hand, constitutes an opportunity for lucrative business of diverse stakeholders. In contrast, plant biofarming is here proposed as a sustainable alternative for the production not only of natural herbal repellents used for malaria prevention but also for the production of sustainable anti-malarial drugs like artemisinin used for primary parasite infection treatments.Artemisinin, a sesquiterpene lactone, is a natural anti-malarial compound that can be found in Artemisia annua plant. However, the low concentration of artemisinin in plant makes this molecule relatively expensive and difficult to meet the worldwide demand of Artemisinin Combination Therapies, especially for economically disadvantaged people in developing countries. The biosynthetic pathway of artemisinin, a process that only takes place in glandular secretory trichomes of A. annua, is relatively well elucidated, and significant efforts using plant genetic engineering have been made to increase the production of this compound. These include studies on diverse transcription factors, which all have been shown to regulate artemisinin genetic pathway and other biological processes. Therefore, genetic manipulation of these genes may be used as a cost-effective potential

  7. Quality of anti-malarials collected in the private and informal sectors in Guyana and Suriname

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    Evans Lawrence

    2012-06-01

    Full Text Available Abstract Background Despite a significant reduction in the number of malaria cases in Guyana and Suriname, this disease remains a major problem in the interior of both countries, especially in areas with gold mining and logging operations, where malaria is endemic. National malaria control programmes in these countries provide treatment to patients with medicines that are procured and distributed through regulated processes in the public sector. However, availability to medicines in licensed facilities (private sector and unlicensed facilities (informal sector is common, posing the risk of access to and use of non-recommended treatments and/or poor quality products. Methods To assess the quality of circulating anti-malarial medicines, samples were purchased in the private and informal sectors of Guyana and Suriname in 2009. The sampling sites were selected based on epidemiological data and/or distance from health facilities. Samples were analysed for identity, content, dissolution or disintegration, impurities, and uniformity of dosage units or weight variation according to manufacturer, pharmacopeial, or other validated method. Results Quality issues were observed in 45 of 77 (58% anti-malarial medicines sampled in Guyana of which 30 failed visual & physical inspection and 18 failed quality control tests. The proportion of monotherapy and ACT medicines failing quality control tests was 43% (13/30 and 11% (5/47 respectively. A higher proportion of medicines sampled from the private sector 34% (11/32 failed quality control tests versus 16% (7/45 in the informal sector. In Suriname, 58 medicines were sampled, of which 50 (86% were Artecom®, the fixed-dose combination of piperaquine-dihydroartemisinin-trimethoprim co-blistered with a primaquine phosphate tablet. All Artecom samples were found to lack a label claim for primaquine, thus failing visual and physical inspection. Conclusions The findings of the studies in both countries point to

  8. Reduction of anti-malarial consumption after rapid diagnostic tests implementation in Dar es Salaam: a before-after and cluster randomized controlled study

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    Swai Ndeniria

    2011-04-01

    Full Text Available Abstract Background Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment. The aim was to assess the effect of implementing malaria rapid diagnostic tests (mRDTs on prescription of anti-malarials in urban Tanzania. Methods The design was a prospective collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in randomly selected health facilities (HF in Dar es Salaam, Tanzania. The participants were all clinicians and their patients in the above health facilities. The intervention consisted of training and introduction of mRDTs in all three hospitals and in six HF. Three HF without mRDTs were selected as matched controls. The use of routine mRDT and treatment upon result was advised for all patients complaining of fever, including children under five years of age. The main outcome measures were: (1 anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention; (2 anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after mRDT implementation. Results Based on routine statistics, the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68% (95%CI 57-80 in intervention and 32% (9-54 in control HF. For quinine vials, the reduction was 63% (54-72 in intervention and an increase of 2.49 times (1.62-3.35 in control HF. Before-and-after cross-sectional surveys showed a similar decrease from 75% to 20% in the proportion of patients receiving anti-malarial treatment (Risk ratio 0.23, 95%CI 0.20-0.26. The cluster randomized analysis showed a considerable difference of anti-malarial prescription between intervention HF (22% and control HF (60% (Risk ratio 0.30, 95%CI 0.14-0.70. Adherence to test result was excellent since only 7% of negative patients received an anti-malarial. However, antibiotic

  9. Substandard anti-malarial drugs in Burkina Faso

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    Sie Ali

    2008-05-01

    Full Text Available Abstract Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers and illicit (market and street vendors, shops sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50% chloroquine, 10/77 (13% pyrimethamine-sulphadoxine, 9/77 (12% quinine, 6/77 (8% amodiaquine, 9/77 (12% artesunate, and 4/77 (5% artemether-lumefantrine. 32/77 (42% drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6% and 27/30 (90.0% samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the

  10. Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries

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    O'Connell Kathryn A

    2011-10-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC, Madagascar, Nigeria, Uganda and Zambia. Methods Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. Results 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets as compared to first-line quality-assured ACT ( Conclusions These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria.

  11. Anti-malarial activity of leaf-extract of hydrangea macrophylla, a common Japanese plant.

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    Kamei K

    2000-10-01

    Full Text Available To find a new anti-malarial medicine derived from natural resources, we examined the leaves of 13 common Japanese plants in vitro. Among them, a leaf-extract of Hydrangea macrophylla, a common Japanese flower, inhibited the parasitic growth of Plasmodium falciparum. The IC50 of Hydrangea macrophylla leaf extract to Plasmodium falciparum was 0.18 microg/ml. The IC50 to NIH 3T3-3 cells, from a normal mouse cell line, was 7.2 microg/ml. Thus, selective toxicity was 40. For the in vivo test, we inoculated Plasmodium berghei, a rodent malaria parasite, to ddY mice and administered the leaf-extract of Hydrangea macrophylla (3.6 mg/0.2 ml orally 3 times a day for 3 days. Malaria parasites did not appear in the blood of in the treated mice, but they did appear in the control group on day 3 or 4 after inoculation with the parasites. When leaf extract was administered to 5 mice 2 times a day for 3 days, malaria parasites did not appear in 4 of the mice but did appear in 1 mouse. In addition, the leaf-extract was administered orally 3 times a day for 3 days to Plasmodium berghei infected mice with a parasitemia of 2.7%. In the latter group, malaria parasites disappeared on day 3 after initiating the treatment, but they appeared again after day 5 or 6. Although we could not cure the mice entirely, we confirmed that the Hydrangea macrophylla leaf extract did contain an anti-malarial substance that can be administered orally.

  12. Anti-Malarial Plants of Jonai, India: an Ethnobotanical Approach

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    Tonlong WANGPAN

    2016-03-01

    Full Text Available North-East India represents a unique ecosystem with treasured medicinal plant wealth closely related with Folk medicines. A large number of plants having medicinal properties and their folk uses have remained confined to the natives of this region. The tribal community of Jonai, Assam was explored to expose the indigenous herbal remedy for malaria. Sixteen antimalarial plants belonging to 13 families were reported. The analysis revealed highest fidelity level (FL value for Ajuga integrifolia (100% followed by Ricinus communis (94%, Alstonia scholaris (88%, Oroxylum indicum (86% and Achyranthes aspera (82%. The percentage of respondent’s knowledge (PRK about anti-malarial plants showed Alstonia scholaris as the most commonly known antimalarial species (53% within this region. Preference ranking (PR unveiled eight species to be very effective against malarial parasite, which includes Allium sativum, Artemisia indica, Azadirachta indica, Carica papaya, Clerodendrum glandulosum, Ocimum tenuiflorum, Oroxylum indicum, Piper longum and Piper nigrum. All medicine preparations are made using water as the medium and are orally administered in the form of crude extract, powder, juice and decoction. Overall analysis suggested Ajuga integrifolia, Achyranthes aspera, Alstonia scholaris, Artemisia indica, Oroxylum indicum and Ricinus communis to be used for the development of novel, economical, effective and ecofriendly herbal formulations for healthcare management.

  13. Assessing the utility of an anti-malarial pharmacokinetic-pharmacodynamic model for aiding drug clinical development

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    Zaloumis Sophie

    2012-08-01

    Full Text Available Abstract Background Mechanistic within-host models relating blood anti-malarial drug concentrations with the parasite-time profile help in assessing dosing schedules and partner drugs for new anti-malarial treatments. A comprehensive simulation study to assess the utility of a stage-specific pharmacokinetic-pharmacodynamic (PK-PD model for predicting within-host parasite response was performed. Methods Three anti-malarial combination therapies were selected: artesunate-mefloquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine. The PK-PD model included parameters to represent the concentration-time profiles of both drugs, the initial parasite burden and distribution across the parasite life cycle, and the parasite multiplication factor due to asexual reproduction. The model also included the maximal killing rate of each drug, and the blood drug concentration associated with half of that killing effect (in vivo EC50, derived from the in vitro IC50, the extent of binding to 0.5% Albumax present in the in vitro testing media, and the drugs plasma protein binding and whole blood to plasma partitioning ratio. All stochastic simulations were performed using a Latin-Hypercube-Sampling approach. Results The simulations demonstrated that the proportion of patients cured was highly sensitive to the in vivo EC50 and the maximal killing rate of the partner drug co-administered with the artemisinin derivative. The in vivo EC50 values that corresponded to on average 95% of patients cured were much higher than the adjusted values derived from the in vitro IC50. The proportion clinically cured was not strongly influenced by changes in the parameters defining the age distribution of the initial parasite burden (mean age of 4 to 16 hours and the parasite multiplication factor every life cycle (ranging from 8 to 12 fold/cycle. The median parasite clearance times, however, lengthened as the standard deviation of the initial parasite burden increased (i

  14. In silico and in vivo anti-malarial studies of 18β glycyrrhetinic acid from Glycyrrhiza glabra.

    Science.gov (United States)

    Kalani, Komal; Agarwal, Jyoti; Alam, Sarfaraz; Khan, Feroz; Pal, Anirban; Srivastava, Santosh Kumar

    2013-01-01

    Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69 µg/ml) anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250 mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.

  15. The biological and clinical activity of anti-malarial drugs in autoimmune disorders.

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    Taherian, Elham; Rao, Anshul; Malemud, Charles J; Askari, Ali D

    2013-01-01

    Chloroquine and hydroxychloroquine are 4-aminoquinoline compounds commonly employed as anti-malarial drugs. Chloroquine and its synthetic analogue, hydroxychloroquine also belong to the disease-modifying anti-rheumatic drug class because these drugs are immunosuppressive. The immunosuppressive activity of chloroquine and hydroxychloroquine is likely to account for their capacity to reduce T-cell and B-cell hyperactivity as well as pro-inflammatory cytokine gene expression. This review evaluated experimental and clinical trials results as well as clinical response data relative to the use of chloroquine and/or hydroxychloroquine as first-line medical therapies in systemic lupus erythematosus, rheumatoid arthritis, primary Sjogren's syndrome, the anti-phospholipid syndrome and in the treatment of sarcoidosis. A primary outcomes measure in these clinical trials was the extent to which chloroquine and/or hydroxychloroquine reduced disease progression or exacerbations and/or the use and dosage of corticosteroids. The relative efficacy of chloroquine and hydroxychloroquine in modifying the clinical course of these autoimmune disorders is balanced against evidence that these drugs induce adverse effects which may reduce their use and effectiveness in the therapy of autoimmune disorders.

  16. Novel Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Anti-malarial Activity in the Mouse Model

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    Booker, Michael L.; Bastos, Cecilia M.; Kramer, Martin L.; Barker, Jr., Robert H.; Skerlj, Renato; Sidhu, Amar Bir; Deng, Xiaoyi; Celatka, Cassandra; Cortese, Joseph F.; Guerrero Bravo, Jose E.; Crespo Llado, Keila N.; Serrano, Adelfa E.; Angulo-Barturen, Iñigo; Jiménez-Díaz, María Belén; Viera, Sara; Garuti, Helen; Wittlin, Sergio; Papastogiannidis, Petros; Lin, Jing-wen; Janse, Chris J.; Khan, Shahid M.; Duraisingh, Manoj; Coleman, Bradley; Goldsmith, Elizabeth J.; Phillips, Margaret A.; Munoz, Benito; Wirth, Dyann F.; Klinger, Jeffrey D.; Wiegand, Roger; Sybertz, Edmund (Leiden-MC); (Puerto Rico); (STPHI); (Harvard); (GSK); (Genzyme); (UTSMC)

    2010-11-22

    Plasmodium falciparum, the causative agent of the most deadly form of human malaria, is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. Dihydroorotate dehydrogenase (DHODH) catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and represents a potential target for anti-malarial therapy. A high throughput screen and subsequent medicinal chemistry program identified a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH from P. falciparum, P. vivax, and P. berghei. The compounds were selective for the parasite enzymes over human DHODH, and x-ray structural data on the analog Genz-667348, demonstrated that species selectivity could be attributed to amino acid differences in the inhibitor-binding site. Compounds from this series demonstrated in vitro potency against the 3D7 and Dd2 strains of P. falciparum, good tolerability and oral exposure in the mouse, and ED{sub 50} values in the 4-day murine P. berghei efficacy model of 13-21 mg/kg/day with oral twice-daily dosing. In particular, treatment with Genz-667348 at 100 mg/kg/day resulted in sterile cure. Two recent analogs of Genz-667348 are currently undergoing pilot toxicity testing to determine suitability as clinical development candidates.

  17. Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries

    Science.gov (United States)

    2011-01-01

    Background Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. Methods Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. Results 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (< 25%). In the public/not-for-profit sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share

  18. Accessibility, availability and affordability of anti-malarials in a rural district in Kenya after implementation of a national subsidy scheme

    Directory of Open Access Journals (Sweden)

    Simiyu Chrispinus

    2011-10-01

    Full Text Available Abstract Background Poor access to prompt and effective treatment for malaria contributes to high mortality and severe morbidity. In Kenya, it is estimated that only 12% of children receive anti-malarials for their fever within 24 hours. The first point of care for many fevers is a local medicine retailer, such as a pharmacy or chemist. The role of the medicine retailer as an important distribution point for malaria medicines has been recognized and several different strategies have been used to improve the services that these retailers provide. Despite these efforts, many mothers still purchase ineffective drugs because they are less expensive than effective artemisinin combination therapy (ACT. One strategy that is being piloted in several countries is an international subsidy targeted at anti-malarials supplied through the retail sector. The goal of this strategy is to make ACT as affordable as ineffective alternatives. The programme, called the Affordable Medicines Facility - malaria was rolled out in Kenya in August 2010. Methods In December 2010, the affordability and accessibility of malaria medicines in a rural district in Kenya were evaluated using a complete census of all public and private facilities, chemists, pharmacists, and other malaria medicine retailers within the Webuye Demographic Surveillance Area. Availability, types, and prices of anti-malarials were assessed. There are 13 public or mission facilities and 97 medicine retailers (registered and unregistered. Results The average distance from a home to the nearest public health facility is 2 km, but the average distance to the nearest medicine retailer is half that. Quinine is the most frequently stocked anti-malarial (61% of retailers. More medicine retailers stocked sulphadoxine-pyramethamine (SP; 57% than ACT (44%. Eleven percent of retailers stocked AMFm subsidized artemether-lumefantrine (AL. No retailers had chloroquine in stock and only five were selling artemisinin

  19. Quality of anti-malarial drugs provided by public and private healthcare providers in south-east Nigeria

    Directory of Open Access Journals (Sweden)

    Uzochukwu Benjamin

    2009-02-01

    Full Text Available Abstract Background There is little existing knowledge about actual quality of drugs provided by different providers in Nigeria and in many sub-Saharan African countries. Such information is important for improving malaria treatment that will help in the development and implementation of actions designed to improve the quality of treatment. The objective of the study was to determine the quality of drugs used for the treatment of malaria in a broad spectrum of public and private healthcare providers. Methods The study was undertaken in six towns (three urban and three rural in Anambra state, south-east Nigeria. Anti-malarials (225 samples, which included artesunate, dihydroartemisinin, sulphadoxine-pyrimethamine (SP, quinine, and chloroquine, were either purchased or collected from randomly selected providers. The quality of these drugs was assessed by laboratory analysis of the dissolution profile using published pharmacopoeial monograms and measuring the amount of active ingredient using high performance liquid chromatography (HPLC. Findings It was found that 60 (37% of the anti-malarials tested did not meet the United States Pharmacopoeia (USP specifications for the amount of active ingredients, with the suspect drugs either lacking the active ingredients or containing suboptimal quantities of the active ingredients. Quinine (46% and SP formulations (39% were among drugs that did not satisfy the tolerance limits published in USP monograms. A total of 78% of the suspect drugs were from private facilities, mostly low-level providers, such as patent medicine dealers (vendors. Conclusion This study found that there was a high prevalence of poor quality drugs. The findings provide areas for public intervention to improve the quality of malaria treatment services. There should be enforced checks and regulation of drug supply management as well as stiffer penalties for people stocking substandard and counterfeit drugs.

  20. Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

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    Newton Paul N

    2011-12-01

    Full Text Available Abstract Background Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. Methods Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis and botanical investigations were performed. Results Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA containing paracetamol (acetaminophen, counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. Conclusions Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.

  1. In silico and in vivo anti-malarial studies of 18β glycyrrhetinic acid from Glycyrrhiza glabra.

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    Komal Kalani

    Full Text Available Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69 µg/ml anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250 mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.

  2. Prescription pattern of anti-malarial drugs in a tertiary care hospital

    Institute of Scientific and Technical Information of China (English)

    Santoshkumar R Jeevangi; Manjunath S; Sharanabasappa M Awanti

    2010-01-01

    Objective:To evaluate the prescribing pattern of anti malarial drugs in a tertiary care hospital. Methods:A prospective cross-sectional study was conducted for 6 months of patients visiting in Basaveshwar Teaching and General Hospital, Gulbarga. Data were analyzed for various drug use indicators. Results: A total of 212 prescriptions were collected, with 136 (64.15%) male and 76 (35.85%) female. There were 128 (60.37%) Plasmodium vivax cases and 84 (39.63%) Plasmodium falciparum cases. All Plasmodium vivax cases were treated with chloroquine alone and among these 16 (12.5%) recieved radical treatment with primaquine along with chloroquine. Among 84 patients with Pasmodium falciparum, 40 patients received single drug such as quinine/mefloquinine/artesunate/arteether. Another 44 patients received multidrug regime like, quinine+artesunate (54.54%), quinine+mefloquine (27.27%) and quinine+arteether (18.18%). Chloroquine was not administered to any of the patients with Plasmodium falciparum malaria. The most common adverse effects with chloroquine were anorexia, nausea, vomiting and tinnitus in 9.37%of the cases. With quinine it was nausea and vomiting in 17.64%, tinnitus in 11.76%and hypoglycemia in 2.1%of cases. Conclusions: Our study found the perennial favorites like chloroquine for Plasmodium vivax and quinine for Plasmodium falciparum were the most effective drug. In the severe Plasmodium falciparum cases the artesunate derivatives and combination of artesunate with quinine/mefloquine were most effective with fewer incidences of side effects.

  3. Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty

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    McKenzie F Ellis

    2010-07-01

    Full Text Available Abstract Background The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs. Such strategies are deployed to best effect before resistance has emerged, under conditions of great uncertainty. Methods Here, the emergence and spread of resistance was modelled using a hybrid framework to evaluate prospective strategies, estimate the time to drug failure, and weigh uncertainty. The waiting time to appearance was estimated as the product of low mutation rates, drug pressure, and parasite population sizes during treatment. Stochastic persistence and the waiting time to establishment were simulated as an evolving branching process. The subsequent spread of resistance was simulated in simple epidemiological models. Results Using this framework, the waiting time to the failure of artemisinin combination therapy (ACT for malaria was estimated, and a policy of multiple first-line therapies (MFTs was evaluated. The models quantify the effects of reducing drug pressure in delaying appearance, reducing the chances of establishment, and slowing spread. By using two first-line therapies in a population, it is possible to reduce drug pressure while still treating the full complement of cases. Conclusions At a global scale, because of uncertainty about the time to the emergence of ACT resistance, there was a strong case for MFTs to guard against early failure. Our study recommends developing operationally feasible strategies for implementing MFTs, such as distributing different ACTs at the clinic and for home-based care, or formulating different ACTs for children and adults.

  4. Saleability of anti-malarials in private drug shops in Muheza, Tanzania

    DEFF Research Database (Denmark)

    Ringsted, Frank M; Massawe, Isolide S; Lemnge, Martha M;

    2011-01-01

    prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. Results......: All surveyed drug shops illicitly sold SP and quinine (QN), and legally amodiaquine (AQ). Calculated monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local brands of SP accounted for 74% of sales volume, compared to AQ (13%), QN (11%) and ACT (2%). Conclusions: In community...... resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp strategy. Further studies are recommended to find out barriers for ACT utilization and preference for self-medication and to train private drug...

  5. Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin

    Directory of Open Access Journals (Sweden)

    Swain Bijay K

    2009-02-01

    Full Text Available Abstract Background Herbal extracts of Andrographis paniculata (AP and Hedyotis corymbosa (HC are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20 and resistant (MRC-pf-303 strains of Plasmodium falciparum for their anti-malarial activity. Methods Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. Results The 50% inhibitory concentration (IC50 of AP (7.2 μg/ml was found better than HC (10.8 μg/ml. Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC and their individual synergism with curcumin (AP+CUR, HC+CUR were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. Conclusion Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.

  6. New developments in anti-malarial target candidate and product profiles.

    Science.gov (United States)

    Burrows, Jeremy N; Duparc, Stephan; Gutteridge, Winston E; Hooft van Huijsduijnen, Rob; Kaszubska, Wiweka; Macintyre, Fiona; Mazzuri, Sébastien; Möhrle, Jörg J; Wells, Timothy N C

    2017-01-13

    A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

  7. CoMFA, CoMSIA, and docking studies on thiolactone-class of potent anti-malarials: identification of essential structural features modulating anti-malarial activity.

    Science.gov (United States)

    Roy, Kuldeep K; Bhunia, Shome S; Saxena, Anil K

    2011-09-01

    The integrated ligand- and structure-based drug design techniques have been applied on a homogeneous dataset of thiolactone-class of potent anti-malarials, to explore the essential structural features for the inhibition of Plasmodium falciparum. Developed CoMFA (q(2) = 0.716) and CoMSIA (q(2) = 0.632) models well explained structure-activity variation in both the training (CoMFA R(2) = 0.948 & CoMSIA R(2) = 0.849) and test set (CoMFA R(2) (pred) = 0.789 & CoMSIA R(2) (pred) = 0.733) compounds. The docking and scoring of the most active compound 10 into the active site of high-resolution (2.35 Å) structure of FabB-TLM binary complex (PDB-ID: 1FJ4) indicated that thiolactone core of this compound forms bifurcated H-bonding with two catalytic residues His298 and His333, and its saturated decyl side group is stabilized by hydrophobic interactions with the residues of a small hydrophobic groove, illustrating that the active site architecture, including two catalytic histidines and a small hydrophobic groove, is vital for protein-ligand interaction. In particular, the length and flexibility of the side group attached to the position 5 of thiolactone have been observed to play a significant role in the interaction with FabB enzyme. These results present scope for rational design of thiolactone-class of compounds that could furnish improved anti-malarial activity.

  8. Anti-malarial effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one and green tea extract on erythrocyte-stage Plasmodium berghei in mice

    Institute of Scientific and Technical Information of China (English)

    Phitsinee; Thipubon; Wachiraporn; Tipsuwan; Chairat; Uthaipibull; Sineenart; Santitherakul; Somdet; Srichiratanakool

    2015-01-01

    Objective: To examine the efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1) iron chelator and green tea extract(GTE) as anti-malarial activity in Plasmodium berghei(P. berghei) infected mice.Methods: The CM1(0–100 mg/kg/day) and GTE(0–100 mg(-)-epigallocatechin 3-gallate equivalent/kg/day) were orally administered to P. berghei infected mice for consecutive 4 days. Parasitized red blood cells(PRBC) were enumerated by using Giemsa staining microscopic method.Results: CM1 lowered percentage of PRBC in dose-dependent manner with an ED50 value of 56.91 mg/kg, when compared with pyrimethamine(PYR)(ED50= 0.76 mg/kg).GTE treatment did not show any inhibition of the malaria parasite growth. In combined treatment, CM1 along with 0.6 mg/kg PYR significantly inhibited the growth of P. berghei in mice while GTE did not enhance the PYR anti-malarial activity.Conclusions: CM1 would be effective per se and synergize with PYR in inhibiting growth of murine malaria parasites, possibly by limiting iron supply from plasma transferrin and host PRBC cytoplasm, and chelating catalytic iron cstitutive in parasites’ mitochondrial cytochromes and cytoplasmic ribonucleotide reductase. CM1 would be a promising adjuvant to enhance PYR anti-malarial activity and minimize the drug resistance.

  9. Anti-malarial effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one and green tea extract on erythrocyte-stage Plasmodium berghei in mice

    Institute of Scientific and Technical Information of China (English)

    Phitsinee Thipubon; Wachiraporn Tipsuwan; Chairat Uthaipibull; Sineenart Santitherakul; Somdet Srichiratanakool

    2015-01-01

    Objective:To examine the efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) iron chelator and green tea extract (GTE) as anti-malarial activity in Plasmodium berghei (P. berghei ) infected mice. Methods:The CM1 (0–100 mg/kg/day) and GTE (0–100 mg (-)-epigallocatechin 3-gallate equivalent/kg/day) were orally administered to P. berghei infected mice for consecutive 4 days. Parasitized red blood cells (PRBC) were enumerated by using Giemsa staining microscopic method. Results: CM1 lowered percentage of PRBC in dose-dependent manner with an ED50 value of 56.91 mg/kg, when compared with pyrimethamine (PYR) (ED50=0.76 mg/kg). GTE treatment did not show any inhibition of the malaria parasite growth. In combined treatment, CM1 along with 0.6 mg/kg PYR significantly inhibited the growth of P. berghei in mice while GTE did not enhance the PYR anti-malarial activity. Conclusions: CM1 would be effective per se and synergize with PYR in inhibiting growth of murine malaria parasites, possibly by limiting iron supply from plasma transferrin and host PRBC cytoplasm, and chelating catalytic iron constitutive in parasites’ mitochondrial cytochromes and cytoplasmic ribonucleotide reductase. CM1 would be a promising adjuvant to enhance PYR anti-malarial activity and minimize the drug resistance.

  10. In silico analysis reveals the anti-malarial potential of quinolinyl chalcone derivatives.

    Science.gov (United States)

    Thillainayagam, Mahalakshmi; Pandian, Lavanya; Murugan, Kumar Kalavathy; Vijayaparthasarathi, Vijayakumar; Sundaramoorthy, Sarveswari; Anbarasu, Anand; Ramaiah, Sudha

    2015-01-01

    In this study, the correlation between chemical structures and various parameters such as steric effects and electrostatic interactions to the inhibitory activities of quinolinyl chalcone derivatives is derived to identify the key structural elements required in the rational design of potent and novel anti-malarial compounds. The molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are carried out on 38 chalcones derivatives using Plasmodium falciparum lactate dehydrogenase (PfLDH) as potential target. Surflex-dock is used to determine the probable binding conformations of all the compounds at the active site of pfLDH and to identify the hydrogen bonding interactions which could be used to alter the inhibitory activities. The CoMFA model has provided statistically significant results with the cross-validated correlation coefficient (q(2)) of .850 and the non-cross-validated correlation coefficient (r(2)) of .912. Standard error of estimation (SEE) is .280 and the optimum number of component is five. The predictive ability of the resultant model is evaluated using a test set comprising of 13 molecules and the predicted r(2) value is .885. The results provide valuable insight for optimization of quinolinyl chalcone derivatives for better anti-malarial therapy.

  11. A framework for assessing the risk of resistance for anti-malarials in development

    Directory of Open Access Journals (Sweden)

    Ding Xavier C

    2012-08-01

    Full Text Available Abstract Resistance is a constant challenge for anti-infective drug development. Since they kill sensitive organisms, anti-infective agents are bound to exert an evolutionary pressure toward the emergence and spread of resistance mechanisms, if such resistance can arise by stochastic mutation events. New classes of medicines under development must be designed or selected to stay ahead in this vicious circle of resistance control. This involves both circumventing existing resistance mechanisms and selecting molecules which are resilient against the development and spread of resistance. Cell-based screening methods have led to a renaissance of new classes of anti-malarial medicines, offering us the potential to select and modify molecules based on their resistance potential. To that end, a standardized in vitro methodology to assess quantitatively these characteristics in Plasmodium falciparum during the early phases of the drug development process has been developed and is presented here. It allows the identification of anti-malarial compounds with overt resistance risks and the prioritization of the most robust ones. The integration of this strategy in later stages of development, registration, and deployment is also discussed.

  12. In vitro and in vivo anti-malarial activity of Boerhavia elegans and Solanum surattense

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    Khodakarim Nastaran

    2010-05-01

    Full Text Available Abstract Background There is an urgent need to identify new anti-malarial drug targets for both prophylaxis and chemotherapy, due to the increasing problem of drug resistance to malaria parasites. In the present study, the aim was to discover novel, effective plant-based extracts for the activity against malaria. Methods Ten plants found in Iran were selected by ethnobotanical survey of medicinal plants. The crude ethanolic extracts were tested for in vitro anti-plasmodial activity against two strains of Plasmodium falciparum: K1 (chloroquine-resistant strain and CY27 (chloroquine-sensitive strain, using the parasite lactate dehydrogenase (pLDH assay. The anti-plasmodial activity of the extracts was also assessed in the 4-day suppressive anti-malarial assay in mice inoculated with Plasmodium berghei (ANKA strain. Crude ethanolic extracts showed good anti-plasmodial activity were further fractionated by partitioning in water and dichloromethane. Results Of 10 plant species assayed, three species: Boerhavia elegans (Choisy, Solanum surattense (Burm.f. and Prosopis juliflora (Sw. showed promising anti-plasmodial activity in vitro (IC50 ≤ 50 μg/ml and in vivo with no toxicity. The dichloromethane fraction of three extracts revealed stronger anti-plasmodial activity than the total extracts. Conclusion Anti-plasmodial activities of extracts of B. elegans and S. surattense are reported for the first time.

  13. The anti-malarial chloroquine overcomes Primary resistance and restores sensitivity to Trastuzumab in HER2-positive breast cancer

    Science.gov (United States)

    Cufí, Sílvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A.

    2013-01-01

    Autophagy may control the de novo refractoriness of HER2 gene-amplified breast carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells originally obtained from a patient who rapidly progressed on trastuzumab ab initio display increased cellular levels of the LC3-II protein—a finding that correlates with increased numbers of autophagosomes—and decreased levels of the autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy. Trastuzumab-refractory cells are in a state of “autophagy addiction” because genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic drug chloroquine impedes autophagic resolution of the accumulation of autophagolysosomes formed in the presence of trastuzumab, cells commit to die by apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine radically suppresses tumor growth by > 90% in a tumor xenograft completely refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may therefore improve outcomes among women with autophagy-addicted HER2-positive breast cancer. PMID:23965851

  14. Natural products as starting points for future anti-malarial therapies: going back to our roots?

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    Wells Timothy NC

    2011-03-01

    Full Text Available Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal

  15. In Silico and In Vivo Anti-Malarial Studies of 18β Glycyrrhetinic Acid from Glycyrrhiza glabra

    Science.gov (United States)

    Kalani, Komal; Agarwal, Jyoti; Alam, Sarfaraz; Khan, Feroz; Pal, Anirban; Srivastava, Santosh Kumar

    2013-01-01

    Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69µg/ml) anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68–100% at doses of 62.5–250mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress. PMID:24086367

  16. A study of toxicity and differential gene expression in murine liver following exposure to anti-malarial drugs: amodiaquine and sulphadoxine-pyrimethamine

    Directory of Open Access Journals (Sweden)

    Rath Srikanta

    2011-05-01

    Full Text Available Abstract Background Amodiaquine (AQ along with sulphadoxine-pyrimethamine (SP offers effective and cheaper treatment against chloroquine-resistant falciparum malaria in many parts of sub-Saharan Africa. Considering the previous history of hepatitis, agranulocytosis and neutrocytopenia associated with AQ monotherapy, it becomes imperative to study the toxicity of co-administration of AQ and SP. In this study, toxicity and resulting global differential gene expression was analyzed following exposure to these drugs in experimental Swiss mice. Methods The conventional markers of toxicity in serum, oxidative stress parameters in tissue homogenates, histology of liver and alterations in global transcriptomic expression were evaluated to study the toxic effects of AQ and SP in isolation and in combination. Results The combination therapy of AQ and SP results in more pronounced hepatotoxicity as revealed by elevated level of serum ALT, AST with respect to their individual drug exposure regimen. Furthermore, alterations in the activity of major antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, indicating the development of oxidative stress, was more significant in AQ+SP combination therapy. cDNA microarray results too showed considerably more perturbed gene expression following combination therapy of AQ and SP as compared to their individual drug treatment. Moreover, a set of genes were identified whose expression pattern can be further investigated for identifying a good biomarker for potential anti-malarial hepatotoxicity. Conclusion These observations clearly indicate AQ+SP combination therapy is hepatotoxic in experimental Swiss mice. Microarray results provide a considerable number of potential biomarkers of anti-malarial drug toxicity. These findings hence will be useful for future drug toxicity studies, albeit implications of this study in clinical conditions need to be monitored with cautions.

  17. Anti-malarial drug artesunate attenuates experimental allergic asthma via inhibition of the phosphoinositide 3-kinase/Akt pathway.

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    Chang Cheng

    Full Text Available BACKGROUND: Phosphoinositide 3-kinase (PI3K/Akt pathway is linked to the development of asthma. Anti-malarial drug artesunate is a semi-synthetic derivative of artemisinin, the principal active component of a medicinal plant Artemisia annua, and has been shown to inhibit PI3K/Akt activity. We hypothesized that artesunate may attenuate allergic asthma via inhibition of the PI3K/Akt signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: Female BALB/c mice sensitized and challenged with ovalbumin (OVA developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Artesunate dose-dependently inhibited OVA-induced increases in total and eosinophil counts, IL-4, IL-5, IL-13 and eotaxin levels in bronchoalveolar lavage fluid. It attenuated OVA-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, IL-17, IL-33 and Muc5ac in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, artesunate blocked epidermal growth factor-induced phosphorylation of Akt and its downstream substrates tuberin, p70S6 kinase and 4E-binding protein 1, and transactivation of NF-κB. Similarly, artesunate blocked the phosphorylation of Akt and its downstream substrates in lung tissues from OVA-challenged mice. Anti-inflammatory effect of artesunate was further confirmed in a house dust mite mouse asthma model. CONCLUSION/SIGNIFICANCE: Artesunate ameliorates experimental allergic airway inflammation probably via negative regulation of PI3K/Akt pathway and the downstream NF-κB activity. These findings provide a novel therapeutic value for artesunate in the treatment of allergic asthma.

  18. Communicating the AMFm message: exploring the effect of communication and training interventions on private for-profit provider awareness and knowledge related to a multi-country anti-malarial subsidy intervention

    Science.gov (United States)

    2014-01-01

    Background The Affordable Medicines Facility - malaria (AMFm), implemented at national scale in eight African countries or territories, subsidized quality-assured artemisinin combination therapy (ACT) and included communication campaigns to support implementation and promote appropriate anti-malarial use. This paper reports private for-profit provider awareness of key features of the AMFm programme, and changes in provider knowledge of appropriate malaria treatment. Methods This study had a non-experimental design based on nationally representative surveys of outlets stocking anti-malarials before (2009/10) and after (2011) the AMFm roll-out. Results Based on data from over 19,500 outlets, results show that in four of eight settings, where communication campaigns were implemented for 5–9 months, 76%-94% awareness of the AMFm ‘green leaf’ logo, 57%-74% awareness of the ACT subsidy programme, and 52%-80% awareness of the correct recommended retail price (RRP) of subsidized ACT were recorded. However, in the remaining four settings where communication campaigns were implemented for three months or less, levels were substantially lower. In six of eight settings, increases of at least 10 percentage points in private for-profit providers’ knowledge of the correct first-line treatment for uncomplicated malaria were seen; and in three of these the levels of knowledge achieved at endline were over 80%. Conclusions The results support the interpretation that, in addition to the availability of subsidized ACT, the intensity of communication campaigns may have contributed to the reported levels of AMFm-related awareness and knowledge among private for-profit providers. Future subsidy programmes for anti-malarials or other treatments should similarly include communication activities. PMID:24495691

  19. Development of a TaqMan Allelic Discrimination Assay for detection of Single Nucleotides Polymorphisms associated with anti-malarial drug resistance

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    Kamau Edwin

    2012-01-01

    Full Text Available Abstract Background Anti-malarial drug resistance poses a threat to current global efforts towards control and elimination of malaria. Several methods are used in monitoring anti-malarial drug resistance. Molecular markers such as single nucleotide polymorphism (SNP for example are increasingly being used to identify genetic mutations related to anti-malarial drug resistance. Several methods are currently being used in analysis of SNP associated with anti-malarial drug resistance and although each one of these methods has unique strengths and shortcoming, there is still need to improve and/or develop new methods that will close the gap found in the current methods. Methods TaqMan Allelic Discrimination assays for detection of SNPs associated with anti-malarial drug resistance were designed for analysis on Applied Biosystems PCR platform. These assays were designed by submitting SNP sequences associated with anti-malarial drug resistance to Applied Biosystems website. Eleven SNPs associated with resistance to anti-malarial drugs were selected and tested. The performance of each SNP assay was tested by creating plasmid DNAs carrying codons of interests and analysing them for analysis. To test the sensitivity and specificity of each SNP assay, 12 clinical samples were sequenced at codons of interest and used in the analysis. Plasmid DNAs were used to establish the Limit of Detection (LoD for each assay. Results Data from genetic profiles of the Plasmodium falciparum laboratory strains and sequence data from 12 clinical samples was used as the reference method with which the performance of the SNP assays were compared to. The sensitivity and specificity of each SNP assay was establish at 100%. LoD for each assay was established at 2 GE, equivalent to less than 1 parasite/μL. SNP assays performed well in detecting mixed infection and analysis of clinical samples. Conclusion TaqMan Allelic Discrimination assay provides a good alternative tool in

  20. Recent progress in the identification and development of anti-malarial agents using virtual screening based approaches.

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    Shah, Priyanka; Tiwari, Sunita; Siddiqi, Mohammad Imran

    2015-01-01

    Malaria has continued to be one of the most perplexing diseases for biological science community around the world due to its prevalent devastating nature and quick developing resistance against the frontline drugs. Artimisinin-based combination therapy (ACT) has been so far found to be among the best therapies against Plasmodium pathogens but alarming emergence of resistance in parasites against every known chemotherapy has prompted the scientific community to step up all the efforts towards development of new and affordable anti-malarial drugs. Computer-aided approaches have received enormous attention in recent years in the field of identification and design of novel drugs. In this review, we summarize recently published research concerning the identification and development of anti-malarial compounds using virtual screening approaches. It would be admirable to discern the successful application of in silico studies for anti-malarial drug discovery hitherto and would certainly help in generating new avenues for pursuing integrated studies between the experimentalists and computational chemists in a systematic manner as a time and cost efficient alternative for future antimalarial drug discovery projects.

  1. Combinatorial pathway engineering for optimized production of the anti-malarial FR900098.

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    Freestone, Todd S; Zhao, Huimin

    2016-02-01

    As resistance to current anti-malarial therapeutics spreads, new compounds to treat malaria are increasingly needed. One promising compound is FR900098, a naturally occurring phosphonate. Due to limitations in both chemical synthesis and biosynthetic methods for FR900098 production, this potential therapeutic has yet to see widespread implementation. Here we applied a combinatorial pathway engineering strategy to improve the production of FR900098 in Escherichia coli by modulating each of the pathway's nine genes with four promoters of different strengths. Due to the large size of the library and the low screening throughput, it was necessary to develop a novel screening strategy that significantly reduced the sample size needed to find an optimal strain. This was done by using biased libraries that localize searching around top hits and home in on high-producing strains. By incorporating this strategy, a significantly improved strain was found after screening less than 3% of the entire library. When coupled with culturing optimization, a strain was found to produce 96 mg/L, a 16-fold improvement over the original strain. We believe the enriched library method developed here can be used on other large pathways that may be difficult to engineer by combinatorial methods due to low screening throughput.

  2. Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo.

    Science.gov (United States)

    Vivas, Livia; Rattray, Lauren; Stewart, Lindsay; Bongard, Emily; Robinson, Brian L; Peters, Wallace; Croft, Simon L

    2008-03-01

    Pyronaridine is a Mannich base anti-malarial with demonstrated efficacy against drug resistant Plasmodium falciparum, P. vivax, P. ovale and P. malariae. However, resistance to pyronaridine can develop quickly when it is used alone but can be considerably delayed when it is administered with artesunate in rodent malaria models. The aim of this study was to evaluate the efficacy of pyronaridine in combination with artesunate against P. falciparum in vitro and in rodent malaria models in vivo to support its clinical application. Pyronaridine showed consistently high levels of in vitro activity against a panel of six P. falciparum drug-sensitive and resistant strains (Geometric Mean IC50=2.24 nM, 95% CI=1.20-3.27). In vitro interactions between pyronaridine and artesunate showed a slight antagonistic trend, but in vivo compared to pyronaridine and artesunate administered alone, the 3:1 ratio of the combination, reduced the ED90 of artesunate by approximately 15.6-fold in a pyronaridine-resistant P. berghei line and by approximately 200-fold in an artesunate-resistant line of P. berghei. Complete cure rates were achieved with doses of the combination above or equal to 8 mg/kg per day against P. chabaudi AS. These results indicate that the combination had an enhanced effect over monotherapy and lower daily doses of artesunate could be used to obtain a curative effect. The data suggest that the combination of pyronaridine and artesunate should have potential in areas of multi-drug resistant malaria.

  3. The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat

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    Lall Varinder K

    2012-12-01

    Full Text Available Abstract Background Mefloquine is an anti-malarial drug that can have neurological side effects. This study examines how mefloquine (MF influences central nervous control of autonomic and respiratory systems using the arterially perfused working heart brainstem preparation (WHBP of the rat. Recordings of nerve activity were made from the thoracic sympathetic chain and phrenic nerve, while heart rate (HR and perfusion pressure were also monitored in the arterially perfused, decerebrate, rat WHBP. MF was added to the perfusate at 1 μM to examine its effects on baseline parameters as well as baroreceptor and chemoreceptor reflexes. Results MF caused a significant, atropine resistant, bradycardia and increased phrenic nerve discharge frequency. Chemoreceptor mediated sympathoexcitation (elicited by addition of 0.1 ml of 0.03% sodium cyanide to the aortic cannula was significantly attenuated by the application of MF to the perfusate. Furthermore MF significantly decreased rate of return to resting HR following chemoreceptor induced bradycardia. An increase in respiratory frequency and attenuated respiratory-related sympathetic nerve discharge during chemoreceptor stimulation was also elicited with MF compared to control. However, MF did not significantly alter baroreceptor reflex sensitivity. Conclusions These studies indicate that in the WHBP, MF causes profound alterations in autonomic and respiratory control. The possibility that these effects may be mediated through actions on connexin 36 containing gap junctions in central neurones controlling sympathetic nervous outflow is discussed.

  4. Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience

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    Sebbag Robert

    2011-05-01

    Full Text Available Abstract Background This case study describes how a public-private partnership initiated to develop a new anti-malarial combination, ASAQ Winthrop, has evolved over time to address issues posed by its effective deployment in the field. Case description In 2002, DNDi created the FACT project to develop two fixed-dose combinations, artesunate-amodiaquine and artesunate-mefloquine, to meet the WHO anti-malarial treatment recommendations and international regulatory agencies approval standards. In 2002, Sanofi-aventis had started a development programme for a fixed-dose combination of artesunate and amodiaquine, to replace its co-blister combination. DNDi and sanofi-aventis joined forces in 2004, with the objective of developing within the shortest possible time frame a non-patented, affordable and easy to use fixed-dose combination of artesunate and amodiaquine adapted to the needs of patients, in particular, those of children. The partners developed Coarsucam®/Artesunate Amodiaquine Winthrop® ("ASAQ Winthrop" which was prequalified by the WHO in 2008. Additional partnerships have since been established by DNDi and sanofi-aventis to ensure: 1 the adoption of this new medicine by malaria-endemic countries, 2 its appropriate usage through a broad range of information tools, and 3 the monitoring of its safety and efficacy in the field through an innovative Risk Management Plan. Discussion and evaluation The partnership between DNDi and sanofi-aventis has enabled the development and pre-qualification of ASAQ Winthrop in a short timeframe. As a result of the multiple collaborations established by the two partners, as of late 2010, ASAQ Winthrop was registered in 30 sub-Saharan African countries and in India, with over 80 million treatments distributed in 21 countries. To date, 10 clinical studies, involving 3432 patients with ASAQ Winthrop were completed to document efficacy and safety issues identified in the Risk Management Plan. Conclusions The

  5. Evaluation of anti-malarial activity of Artemisia turcomanica and A. kopetdaghensis by cell-free β-hematin formation assay

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    M. Mojarrab

    2016-10-01

    Full Text Available Background and objectives:The plants of genus Artemisia (Asteraceae have been conventionally used for prevention and medication of a number of ailments. In the present research, ten extracts with different polarities from aerial parts of two Artemisia species, A. kopetdaghensis and A. turcomanica were evaluated for their potential anti-malarial properties. Methods: The plant materials were extracted successively with petroleum ether (PE, dichloromethane (DCM, ethyl acetate (EtOAC, ethanol, and ethanol-water (1:1 v/v  by cold maceration method. Cell free β-hematin formation assay were used for assessing anti-malarial activity of obtained extracts. Results: DCM extract of A. kopetdaghensis and PE extract of A. turcomanica showed remarkable anti-malarial activity with IC50 values of 1.04±0.02 mg/mL and 0.90±0.27 mg/mL, respectively, compared to positive control (chloroquine, IC50 0.04±0.01 mg/mL. Conclusion:  It seems that the anti-malarial activity of these extracts might be bound up with the presence of compounds with low or medium polarity; hence, this preliminary test indicated that these potent extracts could be considered for further investigations to find new sources of anti-malarial phytochemicals.

  6. Anti-malarial drug quality in Lagos and Accra - a comparison of various quality assessments

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    Bate Roger

    2010-06-01

    Full Text Available Abstract Background Two major cities in West Africa, Accra, the capital of Ghana, and Lagos, the largest city of Nigeria, have significant problems with substandard pharmaceuticals. Both have actively combated the problem in recent years, particularly by screening products on the market using the Global Pharma Health Fund e.V. Minilab® protocol. Random sampling of medicines from the two cities at least twice over the past 30 months allows a tentative assessment of whether improvements in drug quality have occurred. Since intelligence provided by investigators indicates that some counterfeit producers may be adapting products to pass Minilab tests, the results are compared with those from a Raman spectrometer and discrepancies are discussed. Methods Between mid-2007 and early-2010, samples of anti-malarial drugs were bought covertly from pharmacies in Lagos on three different occasions (October 2007, December 2008, February 2010, and from pharmacies in Accra on two different occasions (October 2007, February 2010. All samples were tested using the Minilab® protocol, which includes disintegration and active ingredient assays as well as visual inspection, and most samples were also tested by Raman spectrometry. Results In Lagos, the failure rate in the 2010 sampling fell to 29% of the 2007 finding using the Minilab® protocol, 53% using Raman spectrometry, and 46% using visual inspection. In Accra, the failure rate in the 2010 sampling fell to 54% of the 2007 finding using the Minilab® protocol, 72% using Raman spectrometry, and 90% using visual inspection. Conclusions The evidence presented shows that drug quality is probably improving in both cities, especially Lagos, since major reductions of failure rates over time occur with all means of assessment. Many more samples failed when examined by Raman spectrometry than by Minilab® protocol. The discrepancy is most likely caused by the two techniques measuring different aspects of the medication

  7. Anti-malarial drug safety information obtained through routine monitoring in a rural district of South-Western Senegal

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    Brasseur Philippe

    2012-12-01

    Full Text Available Abstract Background Knowing the safety profile of anti-malarial treatments in routine use is essential; millions of patients receive now artemisinin combination therapy (ACT annually, but the return on information through current systems is as yet inadequate. Cohort event monitoring (CEM is a WHO (World Health Organization-recommended practice; testing its performance and feasibility in routine practice in malaria-endemic is important. Methods A nine-year CEM-based study of the safety of artesunate-amodiaquine (ASAQ at five peripheral health facilities in a rural district of South-western Senegal. Staff (nurses, health workers were trained to collect actively and systematically information on the patient, treatment and events on a purposely designed questionnaire. The occurrence and severity of events was collected before, during and after treatment up to 28 days in order to generate information on all adverse events (AEs as well as treatment-emerging signs/symptoms (TESS. Laboratory tests (haematology, liver and renal was planned for at least 10% of cases. Results During 2001–2009, 3,708 parasitologically-confirmed malaria cases (mean age = 16.0 ± 12.7 years were enrolled (26% and 52% of all and parasitologically-confirmed ASAQ treatments, respectively. Treatment was supervised in 96% of cases. Products changed over time: 49% were a loose combination of individually-packaged products (available 2001–03, 42% co-blistered products (2004–09 and 9% a fixed-dose co-formulation (2006–09; dosing was age-based for 42%, weight-based for 58%. AS and AQ were correctly dosed in 97% and 82% of cases with the loose and 93% and 86% with the fixed combination, but only 50% and 42% with the co-blistered product. Thirty-three per cent (33% of patients had at least one sign/symptom pre-treatment, 12% had at least one AE and 9% a TESS (total events 3,914, 1,144 and 693, respectively. AEs overestimated TESS by 1.2-2 fold (average 1.7. Changes in

  8. Synthesis, characterization of chitosan-tripolyphosphate conjugated chloroquine nanoparticle and its in vivo anti-malarial efficacy against rodent parasite: a dose and duration dependent approach.

    Science.gov (United States)

    Tripathy, Satyajit; Das, Sabyasachi; Chakraborty, Subhankari Prasad; Sahu, Sumanta Kumar; Pramanik, Panchanan; Roy, Somenath

    2012-09-15

    Various strategies to deliver antimalarials using nanocarriers have been evaluated. However, taking into account the peculiarities of malaria parasites, the focus is placed mainly polymer-based chitosan nanocarriers. Our purpose of the study is to develop chitosan-tripolyphosphate (CS-TPP) nanoparticles (NPs) conjugated chloroquine in application for attenuation of Plasmodium berghei infection in Swiss mice. NPs were prepared by ionotropic gelation between CS and sodium TPP. In the study, the interaction of CS and TPP and the presence of chloroquine at the surface of chitosan-TPP NPs have been investigated by means of different methods like FTIR, DLS, and zeta potential. After drug preparation, effective dose of the nanoconjugated chloroquine (Nch) among 100, 250, and 500 mg/kg bw/day, was studied against P. berghei infection in Swiss mice by blood smear staining and biochemical assay of different inflammatory markers, and antioxidant enzyme levels also performed. After evaluating the effective dose, dose-dependent duration study was performed for 5, 10, 15 days. From the present study the maximum effect of Nch was found at 250 mg/kg bw concentration for 15 days treatment. So, this Nch might have potential of application as therapeutic anti-malarial and antioxidant agent.

  9. Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs

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    Pradines Bruno

    2011-10-01

    Full Text Available Abstract Background As a result of widespread chloroquine and sulphadoxine-pyrimethamine resistance, artemisinin-based combination therapy (ACT (which includes artemether-lumefantrine and artesunate-amodiaquine has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Since then, there have been very few reports on the ex vivo susceptibility of Plasmodium falciparum to anti-malarial drugs. To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar. Methods The ex vivo susceptibility of 93 P. falciparum isolates from Dakar was successfully determined using the Plasmodium lactate dehydrogenase (pLDH ELISA for the following drugs: chloroquine (CQ, quinine (QN, mefloquine (MQ, monodesethylamodiaquine (MDAQ, lumefantrine (LMF, dihydroartemisinin (DHA and doxycycline (DOX. Results After transformation of the isolate IC50 in ratio of IC50 according to the susceptibility of the 3D7 reference strain (isolate IC50/3D7 IC50, the prevalence of the in vitro resistant isolates with reduced susceptibility was 50% for MQ, 22% for CQ, 12% for DOX, 6% for both QN and MDAQ and 1% for the drugs LMF and DHA. The highest significant positive correlations were shown between responses to CQ and MDAQ (r = 0.569; P r = 0.511; P r = 0.428; P = 0.0001, LMF and MQ (r = 0.413; P = 0.0002, QN and DHA (r = 0.402; P = 0.0003 and QN and MQ (r = 0.421; P = 0.0001. Conclusions The introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components. However, the prevalence of P. falciparum isolates with reduced susceptibility has increased for both MQ and DOX. Taken together, these data suggest that intensive surveillance of the P. falciparum in vitro susceptibility to anti-malarial drugs in Senegal is required.

  10. Comparing changes in haematologic parameters occurring in patients included in randomized controlled trials of artesunate-amodiaquine vs single and combination treatments of uncomplicated falciparum in sub-Saharan Africa

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    Zwang Julien

    2012-01-01

    Full Text Available Abstract Background Artesunate-amodiaquine (AS&AQ is a widely used artemisinin combination therapy (ACT for falciparum malaria. A comprehensive appreciation of its effects on haematology vs other anti-malarials is needed in view of potential safety liabilities. Methods Individual-patient data analysis conducted on a database from seven randomized controlled trials conducted in sub-Saharan African comparing AS&AQ to reference treatments in uncomplicated falciparum malaria patients of all ages. Haematologic values (white cells total and neutrophil counts, haemoglobin/haematocrit, platelets were analysed as both continuous and categorical variables for their occurrence, (severity grade 1-4 and changes during follow-up. Risks and trends were calculated using multivariate logistic random effect models. Results 4,502 patients (72% p = 0.001. Multivariate analysis showed that the risk of anaemia, thrombocytopaenia, and leucopaenia decreased with follow-up time, while neutropaenia increased; the risk of anaemia and thrombocytopaenia increased with higher baseline parasitaemia and parasitological reappearance. White cells total count was not a good surrogate for neutropaenia. No systematic significant difference between treatments was detected. Older patients were at lower risks. Conclusion The effects of AS&AQ on haematologic parameters were not different from those of other anti-malarial treatments used in sub-Saharan Africa. This analysis provides the basis for a broader evaluation of haematology following anti-malarial treatment. Continuing monitoring of haematologic safety on larger databases is required.

  11. A population genetic model for the initial spread of partially resistant malaria parasites under anti-malarial combination therapy and weak intrahost competition.

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    Yuseob Kim

    Full Text Available To develop public-health policies that extend the lifespan of affordable anti-malarial drugs as effective treatment options, it is necessary to understand the evolutionary processes leading to the origin and spread of mutations conferring drug resistance in malarial parasites. We built a population-genetic model for the emergence of resistance under combination drug therapy. Reproductive cycles of parasites are specified by their absolute fitness determined by clinical parameters, thus coupling the evolutionary-genetic with population-dynamic processes. Initial mutations confer only partial drug-resistance. Therefore, mutant parasites rarely survive combination therapy and within-host competition is very weak among parasites. The model focuses on the early phase of such unsuccessful recurrent mutations. This ends in the rare event of mutants enriching in an infected individual from which the successful spread of resistance over the entire population is initiated. By computer simulations, the waiting time until the establishment of resistant parasites is analysed. Resistance spreads quickly following the first appearance of a host infected predominantly by mutant parasites. This occurs either through a rare transmission of a resistant parasite to an uninfected host or through a rare failure of drugs in removing "transient" mutant alleles. The emergence of resistance is delayed with lower mutation rate, earlier treatment, higher metabolic cost of resistance, longer duration of high drug dose, and higher drug efficacy causing a stronger reduction in the sensitive and resistant parasites' fitnesses. Overall, contrary to other studies' proposition, the current model based on absolute fitness suggests that aggressive drug treatment delays the emergence of drug resistance.

  12. Anti-malarials exert a protective effect while Mestizo patients are at increased risk of developing SLE renal disease: data from a Latin-American cohort

    Science.gov (United States)

    Pons-Estel, Guillermo J.; Alarcón, Graciela S.; Hachuel, Leticia; Boggio, Gabriela; Wojdyla, Daniel; Pascual-Ramos, Virginia; Soriano, Enrique R.; Saurit, Verónica; Cavalcanti, Fernando S.; Guzman, Renato A.; Guibert-Toledano, Marlene; Sauza del Pozo, Maria J.; Amigo, Mary-Carmen; Alva, Magaly; Esteva-Spinetti, Maria H.

    2012-01-01

    Objective. To examine the role of ethnicity and the use of anti-malarials (protective) on lupus renal disease. Methods. A nested case–control study (1:2 proportion, n = 265 and 530) within GLADEL's (Grupo Latino Americano De Estudio de Lupus) longitudinal inception cohort was carried out. The end-point was ACR renal criterion development after diagnosis. Cases and controls were matched for follow-up time (end-point or a comparable time, respectively). Renal disease predictors were examined by univariable and multivariable analyses. Additional analyses were done to determine if the protective effect of anti-malarials persisted after adjusting for intake-associated confounders. Results. Of the cases, 233 (87.9%) were women; their mean (s.d.) age at diagnosis was 28.0 (11.9) years and their median (Q3–Q1 interquartile range) follow-up time for cases and controls was 8.3 months (Q3–Q1: 23.5); 56.6% of the cases and 74.3% of the controls were anti-malarial users. Mestizo ethnicity [odds ratio (OR) 1.72, 95% CI 1.19, 2.48] and hypertension (OR 2.26, 95% CI 1.38, 3.70) were independently associated with a higher risk of renal disease, whereas anti-malarial use (OR 0.39, 95% CI 0.26, 0.58), older age at disease onset (OR 0.98, 95% CI 0.96, 0.99) and female gender (OR 0.56, 95% CI 0.32, 0.99) were negatively associated with such occurrence. After adjusting for variables associated with their intake, the protective effect of anti-malarials on renal disease occurrence persisted (OR 0.38, 95% CI 0.25, 0.58). Conclusion. Mestizo patients are at increased risk of developing renal disease, whereas anti-malarial use protects patients from such an occurrence. PMID:22389125

  13. Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation

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    Kaludov Nikola

    2011-09-01

    Full Text Available Abstract Background Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties. Therapeutic activity, as well as toxicity and other essential properties can be analysed and optimized simultaneously, independently of one another. Such methodology is suitable for a search of novel, non-toxic, active anti-malarial compounds. Methods A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and de novo molecular design. Results Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were discovered and experimentally validated. Twelve compounds were identified in silico and tested in vitro; eight of them showed anti-malarial activity (IC50 ≤ 10 μM, with six being very effective (IC50 ≤ 1 μM, and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a

  14. Characterization and optimization of the haemozoin-like crystal (HLC) assay to determine Hz inhibiting effects of anti-malarial compounds

    OpenAIRE

    2015-01-01

    Background The haem-haemozoin biocrystallization pathway is an attractive target where several efficacious and safe anti-malarial drugs act. Consequently, in vitro haemozoin (Hz) inhibition assays have been developed to identify novel compounds. However, results may differ between assays and often require complex methods or sophisticated infrastructure. The recently reported growth of haemozoin-like crystals (HLC) appears to be a simple alternative although the endproduct is structurally diff...

  15. The potential of anti-malarial compounds derived from African medicinal plants, part I: a pharmacological evaluation of alkaloids and terpenoids.

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    Amoa Onguéné, Pascal; Ntie-Kang, Fidele; Lifongo, Lydia Likowo; Ndom, Jean Claude; Sippl, Wolfgang; Mbaze, Luc Meva'a

    2013-12-13

    Traditional medicine caters for about 80% of the health care needs of many rural populations around the world, especially in developing countries. In addition, plant-derived compounds have played key roles in drug discovery. Malaria is currently a public health concern in many countries in the world due to factors such as chemotherapy faced by resistance, poor hygienic conditions, poorly managed vector control programmes and no approved vaccines. In this review, an attempt has been made to assess the value of African medicinal plants for drug discovery by discussing the anti-malarial virtue of the derived phytochemicals that have been tested by in vitro and in vivo assays. This survey was focused on pure compounds derived from African flora which have exhibited anti-malarial properties with activities ranging from "very active" to "weakly active". However, only the compounds which showed anti-malarial activities from "very active" to "moderately active" are discussed in this review. The activity of 278 compounds, mainly alkaloids, terpenoids, flavonoids, coumarines, phenolics, polyacetylenes, xanthones, quinones, steroids, and lignans have been discussed. The first part of this review series covers the activity of 171 compounds belonging to the alkaloid and terpenoid classes. Data available in the literature indicated that African flora hold an enormous potential for the development of phytomedicines for malaria.

  16. Several Human Cyclin-Dependent Kinase Inhibitors, Structurally Related to Roscovitine, As New Anti-Malarial Agents

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    Sandrine Houzé

    2014-09-01

    Full Text Available In Africa, malaria kills one child each minute. It is also responsible for about one million deaths worldwide each year. Plasmodium falciparum, is the protozoan responsible for the most lethal form of the disease, with resistance developing against the available anti-malarial drugs. Among newly proposed anti-malaria targets, are the P. falciparum cyclin-dependent kinases (PfCDKs. There are involved in different stages of the protozoan growth and development but share high sequence homology with human cyclin-dependent kinases (CDKs. We previously reported the synthesis of CDKs inhibitors that are structurally-related to (R-roscovitine, a 2,6,9-trisubstituted purine, and they showed activity against neuronal diseases and cancers. In this report, we describe the synthesis and the characterization of new CDK inhibitors, active in reducing the in vitro growth of P. falciparum (3D7 and 7G8 strains. Six compounds are more potent inhibitors than roscovitine, and three exhibited IC50 values close to 1 µM for both 3D7 and 7G8 strains. Although, such molecules do inhibit P. falciparum growth, they require further studies to improve their selectivity for PfCDKs.

  17. Assessment of global reporting of adverse drug reactions for anti-malarials, including artemisinin-based combination therapy, to the WHO Programme for International Drug Monitoring

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    Van Erps Jan

    2011-03-01

    Full Text Available Abstract Background In spite of enhanced control efforts, malaria remains a major public health problem causing close to a million deaths annually. With support from several donors, large amounts of artemisinin-based combination therapy (ACT are being deployed in endemic countries raising safety concerns as little is known about the use of ACT in several of the settings where they are deployed. This project was undertaken to profile the provenance of the pharmacovigilance reporting of all anti-malarials, including ACT to the WHO adverse drug reaction (ADR database (Vigibase™ over the past 40 years. Methods The WHO Programme for International Drug Monitoring, the Uppsala Monitoring Centre (UMC provided anonymized extracts of Vigibase™ covering the period 1968-2008. All countries in the programme were clustered according to their malaria control phase and income status. The number of individual case safety reports (ICSRs of anti-malarials was analyzed according to those clusters. Results From 1968 to 2008, 21,312 ICSRs suspecting anti-malarials were received from 64 countries. Low-income countries, that are also malaria-endemic (categorized as priority 1 countries submitted only 1.2% of the ICSRs. Only 60 out of 21,312 ICSRs were related to ACT, 51 of which were coming from four sub-Saharan African countries. Although very few ICSRs involved artemisinin-based compounds, many of the adverse events reported were potentially serious. Conclusions This paper illustrates the low reporting of ADRs to anti-malarials in general and ACT in particular. Most reports were submitted by non-endemic and/or high-income countries. Given the current mix of large donor funding, the insufficient information on safety of these drugs, increasing availability of ACT and artemisinin-based monotherapies in public and private sector channels, associated potential for inappropriate use and finally a pipeline of more than 10 new novel anti-malarials in various stages of

  18. Treatment of malaria from monotherapy to artemisinin-based combination therapy by health professionals in urban health facilities in Yaoundé, central province, Cameroon

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    Bley Daniel

    2009-07-01

    Full Text Available Abstract Background After adoption of artesunate-amodiaquine (AS/AQ as first-line therapy for the treatment of uncomplicated malaria by the malaria control programme, this study was designed to assess the availability of anti-malarial drugs, treatment practices and acceptability of the new protocol by health professionals, in the urban health facilities and drugstores of Yaoundé city, Cameroon. Methods Between April and August 2005, retrospective and current information was collected by consulting registers and interviewing health practitioners in urban health facilities using a structured questionnaire. Results In 2005, twenty-seven trade-named drugs have been identified in drugstores; quinine tablets (300 mg were the most affordable anti-malarial drugs. Chloroquine was restricted to food market places and no generic artemisinin derivative was available in public health centres. In public health facilities, 13.6% of health professionals were informed about the new guidelines; 73.5% supported the use of AS-AQ as first-line therapy. However, 38.6% apprehended its use due to adverse events attributed to amodiaquine. Malaria treatment was mainly based on the diagnosis of fever. Quinine (300 mg tablets was the most commonly prescribed first-line anti-malarial drug in adults (44.5% and pregnant women (52.5%. Artequin® was the most cited artemsinin-based combination therapy (ACT (9.9%. Medical sales representatives were the main sources of information on anti-malarials. Conclusion The use of AS/AQ was not implemented in 2005 in Yaoundé, despite the wide range of anti-malarials and trade-named artemisinin derivatives available. Nevertheless, medical practitioners will support the use of this combination, when it is available in a paediatric formulation, at an affordable price. Training, information and participation of health professionals in decision-making is one of the key elements to improve adherence to new protocol guidelines. This baseline

  19. Genotyping of Plasmodium falciparum using antigenic polymorphic markers and to study anti-malarial drug resistance markers in malaria endemic areas of Bangladesh

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    Akter Jasmin

    2012-11-01

    Full Text Available Abstract Background In the past many regions of Bangladesh were hyperendemic for malaria. Malaria control in the 1960s to 1970s eliminated malaria from the plains but in the Chittagong Hill Tracts remained a difficult to control reservoir. The Chittagong Hill Tracts have areas with between 1 and 10% annual malaria rates, predominately 90-95% Plasmodium falciparum. In Southeast Asia, multiplicity of infection for hypo-endemic regions has been approximately 1.5. Few studies on the genetic diversity of P. falciparum have been performed in Bangladesh. Anderson et al. performed a study in Khagrachari, northern Chittagong Hill Tracts in 2002 on 203 patients and found that parasites had a multiplicity of infection of 1.3 by MSP-1, MSP-2 and GLURP genotyping. A total of 94% of the isolates had the K76T Pfcrt chloroquine resistant genotype, and 70% showed the N86Y Pfmdr1 genotype. Antifolate drug resistant genotypes were high with 99% and 73% of parasites having two or more mutations at the dhfr or dhps loci. Methods Nested and real-time polymerase chain reaction (PCR methods were used to genotype P. falciparum using antigenic polymorphic markers and to study anti-malarial drug resistance markers in malaria endemic areas of Bangladesh. Results The analysis of polymorphic and drug resistant genotype on 33 paired recrudescent infections after drug treatment in the period 2004 to 2008 in the Chittagong Hill Tracts, which is just prior to countrywide provision of artemisinin combination therapy. Overall the multiplicity of infection for MSP-1 was 2.7 with a slightly smaller parasite diversity post-treatment. The 13 monoclonal infections by both GLURP and MSP-1 were evenly divided between pre- and post-treatment. The MSP-1 MAD block was most frequent in 66 of the samples. The prevalence of the K76T PfCRT chloroquine resistant allele was approximately 82% of the samples, while the resistant Pfmdr1 N86Y was present in 33% of the samples. Interestingly, the post-treatment

  20. Factors related to compliance to anti-malarial drug combination: example of amodiaquine/sulphadoxine-pyrimethamine among children in rural Senegal

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    Sow Diarietou

    2009-06-01

    Full Text Available Abstract Background The introduction of new anti-malarial treatment that is effective, but more expensive, raises questions about whether the high level of effectiveness observed in clinical trials can be found in a context of family use. The objective of this study was to determine the factors related to adherence, when using the amodiaquine/sulphadoxine-pyrimethamine (AQ/SP association, a transitory strategy before ACT implementation in Senegal. Methods The study was conducted in five rural dispensaries. Children, between two and 10 years of age, who presented mild malaria were recruited at the time of the consultation and were prescribed AQ/SP. The child's primary caretaker was questioned at home on D3 about treatment compliance and factors that could have influenced his or her adherence to treatment. A logistic regression model was used for the analyses. Results The study sample included 289 children. The adherence rate was 64.7%. Two risks factors for non-adherence were identified: the children's age (8–10 years (ORa = 3.07 [1.49–6.29]; p = 0.004; and the profession of the head of household (retailer/employee versus farmer (ORa = 2.71 [1.34–5.48]; p = 0.006. Previously seeking care (ORa = 0.28 [0.105–0.736], p=0.001] satisfaction with received information (ORa = 0.45 [0.24–0.84]; p = 0.013, and the quality of history taking (ORa = 0.38 [0.21–0.69]; p = 0.001 were significantly associated with good compliance. Conclusion The results of the study show the importance of information and communication between caregivers and health center staff. The experience gained from this therapeutic transition emphasizes the importance of information given to the patients at the time of the consultation and drug delivery in order to improve drug use and thus prevent the emergence of rapid drug resistance.

  1. Longitudinal in vitro surveillance of Plasmodium falciparum sensitivity to common anti-malarials in Thailand between 1994 and 2010

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    Parker Daniel

    2012-08-01

    Full Text Available Abstract Background Drug and multidrug-resistant Plasmodium falciparum malaria has existed in Thailand for several decades. Furthermore, Thailand serves as a sentinel for drug-resistant malaria within the Greater Mekong sub-region. However, the drug resistance situation is highly dynamic, changing quickly over time. Here parasite in vitro drug sensitivity is reported for artemisinin derivatives, mefloquine, chloroquine and quinine, across Thailand. Methods Blood was drawn from patients infected with P. falciparum in seven sentinel provinces along Thai international borders with Cambodia, Myanmar, Laos, and Malaysia. In vitro parasite sensitivity was tested using the World Health Organization’s microtest (mark III (between 1994 and 2002 and the histidine-rich protein-2 (HRP2-based enzyme-linked immunosorbent assay (in 2010. Following World Health Organization protocol, at least 30 isolates were collected for each province and year represented in this study. Where possible, t-tests were used to test for significant differences. Results There appears to be little variation across study sites with regard to parasite sensitivity to chloroquine. Quinine resistance appears to have been rising prior to 1997, but has subsequently decreased. Mefloquine sensitivity appears high across the provinces, especially along the north-western border with Myanmar and the eastern border with Cambodia. Finally, the data suggest that parasite sensitivity to artemisinin and its derivatives is significantly higher in provinces along the north-western border with Myanmar. Conclusions Parasite sensitivity to anti-malarials in Thailand is highly variable over time and largely mirrors official drug use policy. The findings with regard to reduced sensitivity to artemisinin derivatives are supported by recent reports of reduced parasite clearance associated with artemisinin. This trend is alarming since artemisinin is considered the last defence against malaria. Continued

  2. Determination of metabolic profile of anti-malarial trioxane CDRI 99/411 in rat liver microsomes using HPLC.

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    Mishra, Smriti; Manickavasagam, Lakshmi; Jain, Girish Kumar

    2012-01-01

    CDRI 99/411 is a potent 1,2,4-trioxane anti-malarial candidate compound of the Central Drug Research Institute, India. This study aimed to conduct comprehensive in vitro metabolic investigations of CDRI 99/411 to corroborate its preclinical investigations. Preliminary in vitro metabolic investigations were performed to assess the metabolic stability [in vitro half-life (t(1/2) ) and in vitro hepatic intrinsic clearance (Cl(int) )] of CDRI 99/411 in male Sprague-Dawley rat and human liver microsomes using validated high-performance liquid chromatography with photodiode array detector. The observed in vitro t(1/2) of the compound in rat and human liver microsomes was 13 min with in vitro Cl(int) 130.7±25.0 μL/min/mg and 19 min with in vitro Cl(int) 89.3 ± 17.40 μL/min/mg. These observations suggested moderate metabolic degradation and in vitro Cl(int) with insignificant difference (p>0.05) in the metabolic stability profile in rat and human. Hence, in vitro metabolic investigations were performed with rat liver microsomes. It was observed that CDRI 99/411 exhibited sigmoidal kinetics. At nonlinear regression (r ≥ 0.99) EC(50) and Hill slope values were 17 µm and 1.50, respectively. The metabolism of CDRI 99/411 was primarily mediated by CYP3A2 and was inferred by CYP reaction phenotyping with known potent inhibitors. Two metabolites of CDRI 99/411 were detected which were undetectable on incubation with 1-aminobenzotriazole and ketoconazole.

  3. CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine

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    Pybus Brandon S

    2012-08-01

    Full Text Available Abstract Background The 8-aminoquinoline (8AQ drug primaquine (PQ is currently the only approved drug effective against the persistent liver stage of the hypnozoite forming strains Plasmodium vivax and Plasmodium ovale as well as Stage V gametocytes of Plasmodium falciparum. To date, several groups have investigated the toxicity observed in the 8AQ class, however, exact mechanisms and/or metabolic species responsible for PQ’s haemotoxic and anti-malarial properties are not fully understood. Methods In the present study, the metabolism of PQ was evaluated using in vitro recombinant metabolic enzymes from the cytochrome P450 (CYP and mono-amine oxidase (MAO families. Based on this information, metabolite identification experiments were performed using nominal and accurate mass measurements. Results Relative activity factor (RAF-weighted intrinsic clearance values show the relative role of each enzyme to be MAO-A, 2C19, 3A4, and 2D6, with 76.1, 17.0, 5.2, and 1.7% contributions to PQ metabolism, respectively. CYP 2D6 was shown to produce at least six different oxidative metabolites along with demethylations, while MAO-A products derived from the PQ aldehyde, a pre-cursor to carboxy PQ. CYPs 2C19 and 3A4 produced only trace levels of hydroxylated species. Conclusions As a result of this work, CYP 2D6 and MAO-A have been implicated as the key enzymes associated with PQ metabolism, and metabolites previously identified as potentially playing a role in efficacy and haemolytic toxicity have been attributed to production via CYP 2D6 mediated pathways.

  4. Phase I randomized dose-ascending placebo-controlled trials of ferroquine - a candidate anti-malarial drug - in adults with asymptomatic Plasmodium falciparum infection

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    Ospina Salazar Carmen L

    2011-03-01

    Full Text Available Abstract Background The development and spread of drug resistant Plasmodium falciparum strains is a major concern and novel anti-malarial drugs are, therefore, needed. Ferroquine is a ferrocenic derivative of chloroquine with proven anti-malarial activity against chloroquine-resistant and -sensitive P. falciparum laboratory strains. Methods Adult young male aged 18 to 45 years, asymptomatic carriers of P. falciparum, were included in two-dose escalation, double-blind, randomized, placebo-controlled Phase I trials, a single dose study and a multiple dose study aiming to evaluate oral doses of ferroquine from 400 to 1,600 mg. Results Overall, 54/66 patients (40 and 26 treated in the single and multiple dose studies, respectively experienced at least one adverse event, 15 were under placebo. Adverse events were mainly gastrointestinal symptoms such as abdominal pain (16, diarrhoea (5, nausea (13, and vomiting (9, but also headache (11, and dizziness (5. A few patients had slightly elevated liver parameters (10/66 including two patients under placebo. Moderate changes in QTc and morphological changes in T waves were observed in the course of the study. However, no adverse cardiac effects with clinical relevance were observed. Conclusions These phase I trials showed that clinically, ferroquine was generally well-tolerated up to 1,600 mg as single dose and up to 800 mg as repeated dose in asymptomatic young male with P. falciparum infection. Further clinical development of ferroquine, either alone or in combination with another anti-malarial, is highly warranted and currently underway.

  5. Reverse pharmacology for developing an anti-malarial phytomedicine. The example of Argemone mexicana

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    Claudia Simoes-Pires

    2014-12-01

    Reverse pharmacology, also called bedside-to-bench, is a research approach based on the traditional knowledge and relates to reversing the classical laboratory to clinic pathway to a clinic to laboratory practice. It is a trans-disciplinary approach focused on traditional knowledge, experimental observations and clinical experiences. This paper is an overview of the reverse pharmacology approach applied to the decoction of Argemone mexicana, used as an antimalarial traditional medicine in Mali. A. mexicana appeared as the most effective traditional medicine for the treatment of uncomplicated falciparum malaria in Mali, and the clinical efficacy of the decoction was comparable to artesunate–amodiaquine as previously published. Four stages of the reverse pharmacology process will be described here with a special emphasis on the results for stage 4. Briefly, allocryptopine, protopine and berberine were isolated through bioguided fractionation, and had their identity confirmed by spectroscopic analysis. The three alkaloids showed antiparasitic activity in vitro, of which allocryptopine and protopine were selective towards Plasmodium falciparum. Furthermore, the amount of the three active alkaloids in the decoction was determined by quantitative NMR, and preliminary in vivo assays were conducted. On the basis of these results, the reverse pharmacology approach is discussed and further pharmacokinetic studies appear to be necessary in order to determine whether these alkaloids can be considered as phytochemical markers for quality control and standardization of an improved traditional medicine made with this plant.

  6. Synthesis and pharmacokinetics of radioisotope labeled anti-malarial agent in Sprague-Dawley rats

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    Kannanpalli, Pradeep; Park, Sang Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-04-15

    Pyro naridine tetraphosphate is a new synthetic drug which is currently being investigated for use in the treatment of malaria. The main objective of this investigation was to synthesize [{sup 14}C]pyro naridine tetraphosphate and to determine its absorption, distribution, excretion and pharmacokinetics in to male and female Sprague-Dawley rats following a single oral administration (10 mg/kg). To overcome the disadvantages posed by the classical method, a novel and efficient method using microwave irradiation was employed for the synthesis of pyro naridine tetraphosphate. Use of microwave irradiation decreased the reaction time considerably, used less of the starting material and also increased the yield when compared with the classical method. [{sup 14}C]Pyro naridine tetraphosphate thus synthesized had a high degree of purity and showed satisfactory {sup 1}H NMR, {sup 13}C NMR, mass spectra (MS), infrared (IR) and elemental analysis data. The distribution of [{sup 14}C]pyro naridine tetraphosphate in various tissues like the blood, plasma, liver, lung, heart, spleen, kidney, brain, stomach, small intestine and large intestine were determined at 1, 4, 8, 24, 48, 96, 144, 192 and 240 h post administration of the drug to rats. Mass balance excretion of [{sup 14}C]pyro naridine tetraphosphate in urine, faeces and in breath as {sup 14}CO{sub 2} were also determined at different time intervals post administration of the drug. We observed that [{sup 14}C]pyro naridine tetraphosphate was readily absorbed and widely distributed within 1 h following oral administration as it was determined by the presence of radioactivity in various tissues investigated. The absorption, distribution and excretion of the drug was found to be gender independent as both male and female rats showed a similar pattern of radioactivity. [{sup 14}C]Pyro naridine tetraphosphate was absorbed mainly from the small intestine upon oral administration. The major route of excretion for [{sup 14}C

  7. Plasmodium serine hydroxymethyltransferase as a potential anti-malarial target: inhibition studies using improved methods for enzyme production and assay

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    Sopitthummakhun Kittipat

    2012-06-01

    Full Text Available Abstract Background There is an urgent need for the discovery of new anti-malarial drugs. Thus, it is essential to explore different potential new targets that are unique to the parasite or that are required for its viability in order to develop new interventions for treating the disease. Plasmodium serine hydroxymethyltransferase (SHMT, an enzyme in the dTMP synthesis cycle, is a potential target for such new drugs, but convenient methods for producing and assaying the enzyme are still lacking, hampering the ability to screen inhibitors. Methods Production of recombinant Plasmodium falciparum SHMT (PfSHMT and Plasmodium vivax SHMT (PvSHMT, using auto-induction media, were compared to those using the conventional Luria Bertani medium with isopropyl thio-β-D-galactoside (LB-IPTG induction media. Plasmodium SHMT activity, kinetic parameters, and response to inhibitors were measured spectrophotometrically by coupling the reaction to that of 5,10-methylenetetrahydrofolate dehydrogenase (MTHFD. The identity of the intermediate formed upon inactivation of Plasmodium SHMTs by thiosemicarbazide was investigated by spectrophotometry, high performance liquid chromatography (HPLC, and liquid chromatography-mass spectrometry (LC-MS. The active site environment of Plasmodium SHMT was probed based on changes in the fluorescence emission spectrum upon addition of amino acids and folate. Results Auto-induction media resulted in a two to three-fold higher yield of Pf- and PvSHMT (7.38 and 29.29 mg/L compared to that produced in cells induced in LB-IPTG media. A convenient spectrophotometric activity assay coupling Plasmodium SHMT and MTHFD gave similar kinetic parameters to those previously obtained from the anaerobic assay coupling SHMT and 5,10-methylenetetrahydrofolate reductase (MTHFR; thus demonstrating the validity of the new assay procedure. The improved method was adopted to screen for Plasmodium SHMT inhibitors, of which some were originally designed

  8. FlexiChip package: an universal microarray with a dedicated analysis software for high-thoughput SNPs detection linked to anti-malarial drug resistance

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    Dondorp Arjen M

    2009-10-01

    Full Text Available Abstract Background A number of molecular tools have been developed to monitor the emergence and spread of anti-malarial drug resistance to Plasmodium falciparum. One of the major obstacles to the wider implementation of these tools is the absence of practical methods enabling high throughput analysis. Here a new Zip-code array is described, called FlexiChip, linked to a dedicated software program, which largely overcomes this problem. Methods Previously published microarray probes detecting single-nucleotide polymorphisms (SNP associated with parasite resistance to anti-malarial drugs (ResMalChip were adapted for a universal microarray FlexiChip format. To evaluate the overall sensitivity of the FlexiChip package (microarray + software, the results of FlexiChip were compared to ResMalChip microarray, using the same extension probes and with the same PCR products. In both cases, sequence results were used as gold standard to calculate sensitivity and specificity. FlexiChip results obtained with a set of field isolates were then compared to those assessed in an independent reference laboratory. Results The FlexiChip package gave results identical to the ResMalChip results in 92.7% of samples (kappa coefficient 0.8491, with a standard error 0.021 and had a sensitivity of 95.88% and a specificity of 97.68% compared to the sequencing as the reference method. Moreover the method performed well compared to the results obtained in the reference laboratories, with 99.7% of identical results (kappa coefficient 0.9923, S.E. 0.0523. Conclusion Microarrays could be employed to monitor P. falciparum drug resistance markers with greater cost effectiveness and the possibility for high throughput analysis. The FlexiChip package is a promising tool for use in poor resource settings of malaria endemic countries.

  9. Treatment decisions based on scalar and functional baseline covariates.

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    Ciarleglio, Adam; Petkova, Eva; Ogden, R Todd; Tarpey, Thaddeus

    2015-12-01

    The amount and complexity of patient-level data being collected in randomized-controlled trials offer both opportunities and challenges for developing personalized rules for assigning treatment for a given disease or ailment. For example, trials examining treatments for major depressive disorder are not only collecting typical baseline data such as age, gender, or scores on various tests, but also data that measure the structure and function of the brain such as images from magnetic resonance imaging (MRI), functional MRI (fMRI), or electroencephalography (EEG). These latter types of data have an inherent structure and may be considered as functional data. We propose an approach that uses baseline covariates, both scalars and functions, to aid in the selection of an optimal treatment. In addition to providing information on which treatment should be selected for a new patient, the estimated regime has the potential to provide insight into the relationship between treatment response and the set of baseline covariates. Our approach can be viewed as an extension of "advantage learning" to include both scalar and functional covariates. We describe our method and how to implement it using existing software. Empirical performance of our method is evaluated with simulated data in a variety of settings and also applied to data arising from a study of patients with major depressive disorder from whom baseline scalar covariates as well as functional data from EEG are available.

  10. Hepatitis C treatment response kinetics and impact of baseline predictors

    DEFF Research Database (Denmark)

    Lindh, M; Arnholm, B; Eilard, A

    2011-01-01

    Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics...... above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected...

  11. Estimating the Impact of Means-tested Subsidies under Treatment Externalities with Application to Anti-Malarial Bednets

    DEFF Research Database (Denmark)

    Bhattacharya, Debopam; Dupas, Pascaline; Kanaya, Shin

    purchase price, causing free-riding and sub-optimal private procurement, such products may be subsidized in developing countries through means-testing. Owing to associated spillover effects, cost-benefit analysis of such subsidies requires modelling behavioral responses of both the subsidized household......Regular use of effective health-products such as insecticide-treated mosquito nets (ITN) by a household benefits its neighbors by (a) reducing chances of infection and (b) raising awareness about product-effectiveness, thereby increasing product-use. Due to their potential social benefits and high......-dimensional estimated regressors corresponding to continuously distributed location coordinates and makes the inference problem novel. We show that even if individual ITN use unambiguously increases with increasing incidence of subsidy in the neighborhood, ignoring spillovers may over- or under-predict overall ITN use...

  12. Revisiting the relationship between baseline risk and risk under treatment

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    Nony Patrice

    2009-02-01

    Full Text Available Abstract Background In medical practice, it is generally accepted that the 'effect model' describing the relationship between baseline risk and risk under treatment is linear, i.e. 'relative risk' is constant. Absolute benefit is then proportional to a patient's baseline risk and the treatment is most effective among high-risk patients. Alternatively, the 'effect model' becomes curvilinear when 'odds ratio' is considered to be constant. However these two models are based on purely empirical considerations, and there is still no theoretical approach to support either the linear or the non-linear relation. Presentation of the hypothesis From logistic and sigmoidal Emax (Hill models, we derived a phenomenological model which includes the possibility of integrating both beneficial and harmful effects. Instead of a linear relation, our model suggests that the relationship is curvilinear i.e. the moderate-risk patients gain most from the treatment in opposition to those with low or high risk. Testing the hypothesis Two approaches can be proposed to investigate in practice such a model. The retrospective one is to perform a meta-analysis of clinical trials with subgroups of patients including a great range of baseline risks. The prospective one is to perform a large clinical trial in which patients are recruited according to several prestratified diverse and high risk groups. Implications of the hypothesis For the quantification of the treatment effect and considering such a model, the discrepancy between odds ratio and relative risk may be related not only to the level of risk under control conditions, but also to the characteristics of the dose-effect relation and the amount of dose administered. In the proposed approach, OR may be considered as constant in the whole range of Rc, and depending only on the intrinsic characteristics of the treatment. Therefore, OR should be preferred rather than RR to summarize information on treatment efficacy.

  13. Finding parasites and finding challenges: improved diagnostic access and trends in reported malaria and anti-malarial drug use in Livingstone district, Zambia

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    Masaninga Freddie

    2012-10-01

    Full Text Available Abstract Background Understanding the impact of malaria rapid diagnostic test (RDT use on management of acute febrile disease at a community level, and on the consumption of anti-malarial medicines, is critical to the planning and success of scale-up to universal parasite-based diagnosis by health systems in malaria-endemic countries. Methods A retrospective study of district-wide community-level RDT introduction was conducted in Livingstone District, Zambia, to assess the impact of this programmed on malaria reporting, incidence of mortality and on district anti-malarial consumption. Results Reported malaria declined from 12,186 cases in the quarter prior to RDT introduction in 2007 to an average of 12.25 confirmed and 294 unconfirmed malaria cases per quarter over the year to September 2009. Reported malaria-like fever also declined, with only 4,381 RDTs being consumed per quarter over the same year. Reported malaria mortality declined to zero in the year to September 2009, and all-cause mortality declined. Consumption of artemisinin-based combination therapy (ACT dropped dramatically, but remained above reported malaria, declining from 12,550 courses dispensed by the district office in the quarter prior to RDT implementation to an average of 822 per quarter over the last year. Quinine consumption in health centres also declined, with the district office ceasing to supply due to low usage, but requests for sulphadoxine-pyrimethamine (SP rose to well above previous levels, suggesting substitution of ACT with this drug in RDT-negative cases. Conclusions RDT introduction led to a large decline in reported malaria cases and in ACT consumption in Livingstone district. Reported malaria mortality declined to zero, indicating safety of the new diagnostic regime, although adherence and/or use of RDTs was still incomplete. However, a deficiency is apparent in management of non-malarial fever, with inappropriate use of a low-cost single dose drug, SP

  14. A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers

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    Oyoo George O

    2011-03-01

    Full Text Available Abstract Background Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. Methods Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. Results The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product were reported. The maximum concentration (Cmax was 160-200 nM and after 6 hours, the effective concentration (Ceff was Conclusion Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.

  15. 3D structure and immunogenicity of Plasmodium falciparum sporozoite induced associated protein peptides as components of fully-protective anti-malarial vaccine.

    Science.gov (United States)

    Alba, Martha P; Almonacid, Hannia; Calderón, Dayana; Chacón, Edgar A; Poloche, Luis A; Patarroyo, Manuel A; Patarroyo, Manuel E

    2011-12-16

    SIAP-1 and SIAP-2 are proteins which are implicated in early events involving Plasmodium falciparum infection of the Anopheles mosquito vector and the human host. High affinity HeLa and HepG2 cell binding conserved peptides have been previously identified in these proteins, i.e. SIAP-1 34893 ((421)KVQGLSYLLRRKNGTKHPVY(440)) and SIAP-1 34899 ((541)YVLNSKLLNSRSFDKFKWIQ(560)) and SIAP-2 36879 ((181)LLLYSTNSEDNLDISFGELQ(200)). When amino acid sequences have been properly modified (replacements shown in bold) they have induced high antibody titres against sporozoites in Aotus monkeys (assessed by IFA) and in the corresponding recombinant proteins (determined by ELISA and Western blot). (1)H NMR studies of these conserved native and modified high activity binding peptides (HABPs) revealed that all had α-helical structures in different locations and lengths. Conserved and corresponding modified HABPs displayed different lengths between the residues fitting into MHCII molecule pockets 1-9 and different amino acid orientation based on their different HLA-DRβ1(∗) binding motifs and binding registers, suggesting that such modifications were associated with making them immunogenic. The results suggested that these modified HAPBs could be potential targets for inclusion as components of a fully-effective, minimal sub-unit based, multi-epitope, and multistage anti-malarial vaccine.

  16. Exposure to anti-malarial drugs and monitoring of adverse drug reactions using toll-free mobile phone calls in private retail sector in Sagamu, Nigeria: implications for pharmacovigilance

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    Ogunwande Isiaka A

    2011-08-01

    Full Text Available Abstract Background Adverse drug reactions (ADRs contribute to ill-health or life-threatening outcomes of therapy during management of infectious diseases. The exposure to anti-malarial and use of mobile phone technology to report ADRs following drug exposures were investigated in Sagamu - a peri-urban community in Southwest Nigeria. Methods Purchase of medicines was actively monitored for 28 days in three Community Pharmacies (CP and four Patent and Proprietary Medicine Stores (PPMS in the community. Information on experience of ADRs was obtained by telephone from 100 volunteers who purchased anti-malarials during the 28-day period. Results and Discussion A total of 12,093 purchases were recorded during the period. Antibiotics, analgesics, vitamins and anti-malarials were the most frequently purchased medicines. A total of 1,500 complete courses of anti-malarials were purchased (12.4% of total purchases; of this number, purchases of sulphadoxine-pyrimethamine (SP and chloroquine (CQ were highest (39.3 and 25.2% respectiuvely. Other anti-malarials purchased were artesunate monotherapy (AS - 16.1%, artemether-lumefantrine (AL 10.0%, amodiaquine (AQ - 6.6%, quinine (QNN - 1.9%, halofantrine (HF - 0.2% and proguanil (PR - 0.2%. CQ was the cheapest (USD 0.3 and halofantrine the most expensive (USD 7.7. AL was 15.6 times ($4.68 more expensive than CQ. The response to mobile phone monitoring of ADRs was 57% in the first 24 hours (day 1 after purchase and decreased to 33% by day 4. Participants in this monitoring exercise were mostly with low level of education (54%. Conclusion The findings from this study indicate that ineffective anti-malaria medicines including monotherapies remain widely available and are frequently purchased in the study area. Cost may be a factor in the continued use of ineffective monotherapies. Availability of a toll-free telephone line may facilitate pharmacovigilance and follow up of response to medicines in a resource

  17. Development of ELISA-based methods to measure the anti-malarial drug chloroquine in plasma and in pharmaceutical formulations

    DEFF Research Database (Denmark)

    Khalil, Insaf F; Alifrangis, Michael; Recke, Camilla

    2011-01-01

    In Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ) remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1 ...... resistance. The aim of this study was to develop an inexpensive, simple antibody-based ELISA to measure CQ concentrations in tablets and in plasma.......In Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ) remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1...

  18. Development of ELISA-based methods to measure the anti-malarial drug chloroquine in plasma and in pharmaceutical formulations

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    Ronn Anita

    2011-08-01

    Full Text Available Abstract Background In Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1 therapeutic agent. There is a dire need to continue monitoring quality of CQ as there is a major influx of substandard and fake formulations into malaria-endemic countries. The use of fake/substandard drugs will result in sub-therapeutic levels endangering the patient and possibly select for parasite resistance. The aim of this study was to develop an inexpensive, simple antibody-based ELISA to measure CQ concentrations in tablets and in plasma. Methods A monoclonal antibody (MAb that reacts with the N-side chain of the CQ molecule was prepared by use of a CQ analogue. A specific and reliable ELISA for detection of CQ was developed. The developed assay was validated by measuring CQ in tablets sold in Denmark, India and Sudan. Furthermore, kinetics of CQ concentrations in plasma of four volunteers, who ingested two tablets of Malarex® containing, 250 mg CQ base, were measured before drug intake, three hours later and thereafter at days 1, 3, 7, 14, 21 and 28. The same plasma samples were simultaneously measured by high performance liquid chromatography (HPLC. Results The ELISA proved an easy-to-handle and very sensitive tool for the detection of CQ with a lower limit of detection at 3.9 ng/ml. ELISA levels of CQ in plasma showed high agreement with the levels obtained by HPLC (r = 0.98. The specificity in the negative control group was 100%. Conclusion The developed ELISA can be used for quality screening of CQ in pharmaceutical formulations and for drug monitoring in malaria and in other infectious diseases, such as HIV, where CQ proved to be an effective therapeutic agent. The methodology has been exploited to develop monoclonal

  19. Preclinical models for neuroblastoma: establishing a baseline for treatment.

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    Tal Teitz

    Full Text Available BACKGROUND: Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system. PRINCIPAL FINDINGS: Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents. SIGNIFICANCE: The studies suggest that use of both the TH-NMYC model of neuroblastoma and the

  20. Treatment of malaria from monotherapy to artemisinin-based combination therapy by health professionals in rural health facilities in southern Cameroon

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    Bley Daniel

    2009-07-01

    Full Text Available Abstract Background One year after the adoption of artesunate-amodiaquine (AS/AQ as first-line therapy for the treatment of uncomplicated malaria, this study was designed to assess the treatment practices regarding anti-malarial drugs at health facilities in four rural areas in southern Cameroon. Methods Between April and August 2005, information was collected by interviewing fifty-two health professionals from twelve rural health facilities, using a structured questionnaire. Results In 2005, only three anti-malarial drugs were used in rural health facilities, including: amodiaquine, quinine and sulphadoxine-pyrimethamine. Only 2.0% of the health professionals prescribed the recommended AS/AQ combination. After reading the treatment guidelines, 75.0% were in favour of the treatment protocol with the following limitations: lack of paediatric formulations, high cost and large number of tablets per day. Up to 21.0% of professionals did not prescribe AS/AQ because of the level of adverse events attributed to the use of amodiaquine as monotherapy. Conclusion The present study indicates that AS/AQ was not available in the public health facilities at the time of the study, and health practitioners were not informed about the new treatment guidelines. Results of qualitative analysis suggest that prescribers should be involved as soon as possible in projects related to the optimization of treatment guidelines and comply with new drugs. Adapted formulations should be made available at the international level and implemented locally before new drugs and treatments are proposed through a national control programme. This baseline information will be useful to monitor progresses in the implementation of artemisinin-based combination therapy in Cameroon.

  1. Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso

    DEFF Research Database (Denmark)

    Diarra, Amidou; Nebie, Issa; Tiono, Alfred

    2012-01-01

    of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. METHODS: Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child...... to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. RESULTS: IgG levels to MSP3 were always higher in the successfully treated......: Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease....

  2. Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?

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    Angus G Jones

    Full Text Available Baseline HbA1c is a major predictor of response to glucose lowering therapy and therefore a potential confounder in studies aiming to identify other predictors. However, baseline adjustment may introduce error if the association between baseline HbA1c and response is substantially due to measurement error and regression to the mean. We aimed to determine whether studies of predictors of response should adjust for baseline HbA1c.We assessed the relationship between baseline HbA1c and glycaemic response in 257 participants treated with GLP-1R agonists and assessed whether it reflected measurement error and regression to the mean using duplicate 'pre-baseline' HbA1c measurements not included in the response variable. In this cohort and an additional 2659 participants treated with sulfonylureas we assessed the relationship between covariates associated with baseline HbA1c and treatment response with and without baseline adjustment, and with a bias correction using pre-baseline HbA1c to adjust for the effects of error in baseline HbA1c.Baseline HbA1c was a major predictor of response (R2 = 0.19,β = -0.44,p<0.001.The association between pre-baseline and response was similar suggesting the greater response at higher baseline HbA1cs is not mainly due to measurement error and subsequent regression to the mean. In unadjusted analysis in both cohorts, factors associated with baseline HbA1c were associated with response, however these associations were weak or absent after adjustment for baseline HbA1c. Bias correction did not substantially alter associations.Adjustment for the baseline HbA1c measurement is a simple and effective way to reduce bias in studies of predictors of response to glucose lowering therapy.

  3. The acceptability of intermittent screening and treatment versus intermittent preventive treatment during pregnancy: results from a qualitative study in Northern Ghana

    NARCIS (Netherlands)

    Pell, C.; Meñaca, A.; Chatio, S.; Hodgson, A.; Tagbor, H.; Pool, R.

    2014-01-01

    Background: Affecting mother and child, malaria during pregnancy (MiP) provokes a double morbidity and mortality burden. Within a package of interventions to prevent MiP in endemic areas, the WHO currently recommends intermittent preventive treatment (IPTp). Concerns about anti-malarial resistance h

  4. [Current view on chloroquine derivative treatment from rheumatologist perspective and possible ocular side effects].

    Science.gov (United States)

    Pawlak-Buś, Katarzyna; Gaca-Wysocka, Magdalena; Grzybowski, Andrzej; Leszczyński, Piotr

    2016-03-01

    Anti-malarial drugs specifically hydroxychloroquine (HCQ) or chloroquine (CQ) are very effective in treating and preventing the symptoms of systemic lupus erythematosus and other connective tissue diseases. These medications have shown to improve joint and muscle pain and arthritis, skin rashes, fatique, fever and also to control systemic signs of lupus as pericarditis or pleuritis. Shortterm and long-term treatment reduce cholesterol and have anti-platelet effect with decreasing risk of cardiovascular disease. The lupus patients on anti-malarials have also lower risk of cumulative organ damage due to reduce the amount of steroids. They may help to decrease lupus flares, mortality and are the key to controlling lupus long term outcome. Some lupus patients should be on anti-malarials for the rest of their life. For this reason, the key question is weather these drugs are absolutely safe and can be long term used in all lupus patients as a background therapy? Potential non-specific side effects occur very rare and are usually minor and last for short period. The major concerns are retinal deposits damage which could be potential reversible especially during hydroxychloroquine treatment. Nevertheless, ophthalmologist examination is still needed before starting to take HCQ or CQ and at to follow-up visits every 6-12 months. In conclusion it seems that anti-malarials are safe and have more clinical benefits than risks and from rheumatologist point of view should be more widely use in all lupus patients.

  5. Adherence to and acceptability of artemether-lumefantrine as first-line anti-malarial treatment: evidence from a rural community in Tanzania

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    Schlienger Raymond

    2010-02-01

    Full Text Available Abstract Background Controlled clinical trials have shown that a six-dose regimen of artemether-lumefantrine (AL therapy for uncomplicated Plasmodium falciparum malaria results in cure rates >95% with good tolerability. Materials and methods A prospective study was carried out to document the adherence to and acceptability of AL administration. This was undertaken in the context of the ALIVE study, a prospective, community-based, observational study in a rural, malaria-endemic area of Tanzania. Following microscopic confirmation of P. falciparum infection, the first AL dose was taken under supervision, with the subsequent five doses taken unsupervised at home. Patients were randomized to receive a home-based assessment close to the scheduled time for one of the unsupervised doses, but were blinded to which follow-up visit they had been allocated. A structured questionnaire was administered by trained staff and AL consumption was confirmed by inspection of blister packs. Results A total of 552 patients were recruited of whom 352 (63.8% were Discussion Factors contributing to adherence were likely to be helpful packaging, pictorial dosing instructions and patients' conviction that AL is effective. Conclusion Adherence to the dosing regimen and timing of AL administration was very good.

  6. Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso

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    Diarra Amidou

    2012-03-01

    Full Text Available Abstract Background Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. Methods Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. Results IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP. Conclusion Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease.

  7. Bayesian inference of baseline fertility and treatment effects via a crop yield-fertility model.

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    Hungyen Chen

    Full Text Available To effectively manage soil fertility, knowledge is needed of how a crop uses nutrients from fertilizer applied to the soil. Soil quality is a combination of biological, chemical and physical properties and is hard to assess directly because of collective and multiple functional effects. In this paper, we focus on the application of these concepts to agriculture. We define the baseline fertility of soil as the level of fertility that a crop can acquire for growth from the soil. With this strict definition, we propose a new crop yield-fertility model that enables quantification of the process of improving baseline fertility and the effects of treatments solely from the time series of crop yields. The model was modified from Michaelis-Menten kinetics and measured the additional effects of the treatments given the baseline fertility. Using more than 30 years of experimental data, we used the Bayesian framework to estimate the improvements in baseline fertility and the effects of fertilizer and farmyard manure (FYM on maize (Zea mays, barley (Hordeum vulgare, and soybean (Glycine max yields. Fertilizer contributed the most to the barley yield and FYM contributed the most to the soybean yield among the three crops. The baseline fertility of the subsurface soil was very low for maize and barley prior to fertilization. In contrast, the baseline fertility in this soil approximated half-saturated fertility for the soybean crop. The long-term soil fertility was increased by adding FYM, but the effect of FYM addition was reduced by the addition of fertilizer. Our results provide evidence that long-term soil fertility under continuous farming was maintained, or increased, by the application of natural nutrients compared with the application of synthetic fertilizer.

  8. Improvements in access to malaria treatment in Tanzania following community, retail sector and health facility interventions -- a user perspective

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    Obrist Brigit

    2010-06-01

    Full Text Available Abstract Background The ACCESS programme aims at understanding and improving access to prompt and effective malaria treatment. Between 2004 and 2008 the programme implemented a social marketing campaign for improved treatment-seeking. To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO was created in Tanzania in 2006. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP to artemether-lumefantrine (ALu in 2007 and subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on understanding and treatment of malaria was studied in rural Tanzania. The data also enabled an investigation of the determinants of access to treatment. Methods Three treatment-seeking surveys were conducted in 2004, 2006 and 2008 in the rural areas of the Ifakara demographic surveillance system (DSS and in Ifakara town. Each survey included approximately 150 people who had suffered a fever case in the previous 14 days. Results Treatment-seeking and awareness of malaria was already high at baseline, but various improvements were seen between 2004 and 2008, namely: better understanding causes of malaria (from 62% to 84%; an increase in health facility attendance as first treatment option for patients older than five years (27% to 52%; higher treatment coverage with anti-malarials (86% to 96% and more timely use of anti-malarials (80% to 93-97% treatments taken within 24 hrs. Unfortunately, the change of treatment policy led to a low availability of ALu in the private sector and, therefore, to a drop in the proportion of patients taking a recommended malaria treatment (85% to 53%. The availability of outlets (health facilities or drug shops is the most important determinant of whether patients receive prompt and effective treatment, whereas affordability and accessibility contribute to a lesser extent. Conclusions An

  9. Mapping the genome of Plasmodium falciparum on the drug-like chemical space reveals novel anti-malarial targets and potential drug leads

    DEFF Research Database (Denmark)

    Jensen, Kasper; Plichta, Damian Rafal; Panagiotou, Gianni;

    2012-01-01

    The parasite Plasmodium falciparum is the main agent responsible for malaria. In this study, we exploited a recently published chemical library from GlaxoSmithKline (GSK) that had previously been confirmed to inhibit parasite growth of the wild type (3D7) and the multi-drug resistance (D2d) strains......, in order to uncover the weak links in the proteome of the parasite. We predicted 293 proteins of P. falciparum, including the six out of the seven verified targets for P. falciparum malaria treatment, as targets of 4645 GSK active compounds. Furthermore, we prioritized druggable targets, based on a number...... on integration of available chemical-protein and protein-protein interaction data. Our work suggests that a large number of the P. falciparum proteome is potentially druggable and could therefore serve as novel drug targets in the fight against malaria. At the same time, prioritized compounds from the GSK...

  10. Low-dose budesonide treatment improves lung function in patients with infrequent asthma symptoms at baseline

    DEFF Research Database (Denmark)

    Reddel, H. K.; Busse, W. W.; Pedersen, Søren;

    2015-01-01

    in patients with less frequent symptoms at presentation. This was investigated in a post-hoc analysis of the multinational inhaled Steroid Treatment As Regular Therapy in early asthma (START) study.2 METHODS: Patients aged 4-66 years (median 21 years) with a history of recent-onset mild asthma (11 years......RATIONALE: Inhaled corticosteroids (ICS) are highly effective in low doses for improving asthma outcomes, including lung function. In the past, ICS treatment was recommended for patients with 'persistent' asthma, defined by symptoms >2 days/week.1 However, evidence is lacking for the benefit of ICS...... symptom frequency groups (Figure). CONCLUSIONS: Long-term, once-daily, low-dose budesonide treatment plus usual asthma medication improves lung function in patients with mild, recent-onset asthma. These beneficial effects were seen even in patients with the lowest baseline asthma symptom frequency (0...

  11. Minimal sufficient balance-a new strategy to balance baseline covariates and preserve randomness of treatment allocation.

    Science.gov (United States)

    Zhao, Wenle; Hill, Michael D; Palesch, Yuko

    2015-12-01

    In many clinical trials, baseline covariates could affect the primary outcome. Commonly used strategies to balance baseline covariates include stratified constrained randomization and minimization. Stratification is limited to few categorical covariates. Minimization lacks the randomness of treatment allocation. Both apply only to categorical covariates. As a result, serious imbalances could occur in important baseline covariates not included in the randomization algorithm. Furthermore, randomness of treatment allocation could be significantly compromised because of the high proportion of deterministic assignments associated with stratified block randomization and minimization, potentially resulting in selection bias. Serious baseline covariate imbalances and selection biases often contribute to controversial interpretation of the trial results. The National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Trial and the Captopril Prevention Project are two examples. In this article, we propose a new randomization strategy, termed the minimal sufficient balance randomization, which will dually prevent serious imbalances in all important baseline covariates, including both categorical and continuous types, and preserve the randomness of treatment allocation. Computer simulations are conducted using the data from the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Trial. Serious imbalances in four continuous and one categorical covariate are prevented with a small cost in treatment allocation randomness. A scenario of simultaneously balancing 11 baseline covariates is explored with similar promising results. The proposed minimal sufficient balance randomization algorithm can be easily implemented in computerized central randomization systems for large multicenter trials.

  12. Treatment of malaria from monotherapy to artemisinin-based combination therapy by health professionals in urban health facilities in Yaoundé, central province, Cameroon

    OpenAIRE

    Bley Daniel; Malvy Denis; Vernazza-Licht Nicole; Gausseres Mathieu; Sayang Collins; Millet Pascal

    2009-01-01

    Abstract Background After adoption of artesunate-amodiaquine (AS/AQ) as first-line therapy for the treatment of uncomplicated malaria by the malaria control programme, this study was designed to assess the availability of anti-malarial drugs, treatment practices and acceptability of the new protocol by health professionals, in the urban health facilities and drugstores of Yaoundé city, Cameroon. Methods Between April and August 2005, retrospective and current information was collected by cons...

  13. Baseline results of the first malaria indicator survey in Iran at the health facility level

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    Taghizadeh-Asl Rahim

    2011-10-01

    Full Text Available Abstract Background Malaria continues to be a global public health challenge, particularly in developing countries. Delivery of prompt and effective diagnosis and treatment of malaria cases, detection of malaria epidemics within one week of onset and control them in less than a month, regular disease monitoring and operational classification of malaria are among the major responsibilities of the national malaria programme. The study was conducted to determine these indicators at the different level of primary health care facilities in malaria-affected provinces of Iran Methods In this survey, data was collected from 223 health facilities including health centres, malaria posts, health houses and hospitals as well as the profile of all 5, 836 recorded malaria cases in these facilities during the year preceding the survey. Descriptive statistics (i.e. frequencies, percentages were used to summarize the results and Chi square test was used to analyse data. Results All but one percent of uncomplicated cases took appropriate and correctly-dosed of anti-malarial drugs in accordance to the national treatment guideline. A larger proportion of patients [85.8%; 95% CI: 84.8 - 86.8] were also given complete treatment including anti-relapse course, in line with national guidelines. About one third [35.0%; 95% CI: 33.6 - 36.4] of uncomplicated malaria cases were treated more than 48 hours after first symptoms onset. Correspondingly, half of severe malaria cases took recommended anti-malarial drugs for severe or complicated disease more than 48 hours of onset of first symptoms. The latter cases had given regular anti-malarial drugs promptly. The majority of malaria epidemics [97%; 95% CI: 90.6 - 100] in study areas were detected within one week of onset, but only half of epidemics were controlled within four weeks of detection. Just half of target districts had at least one health facility/emergency site with adequate supply and equipment stocks. Nevertheless

  14. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

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    Miltiadis K. Tsilimbaris

    2016-01-01

    Full Text Available Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF therapy in the treatment of neovascular age-related macular degeneration (nAMD and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

  15. Dolutegravir treatment response by baseline viral load and NRTI backbone in treatment-naïve HIV-infected individuals

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    C Small

    2012-11-01

    Full Text Available Background: In two 48-week studies in naïve subjects, dolutegravir with NRTI of choice has shown non-inferiority to raltegravir and, with ABC/3TC, superiority to Atripla. Factors that influenced choice of NRTIs included viral load, resistance and safety. Methods: We analysed response rates and time to virologic failure by NRTI backbone and baseline viral load in the pivotal DTG-naïve studies. SPRING-2 randomized participants to DTG 50 mg QD or RAL 400 mg BID, each in combination with investigator-selected NRTIs (TDF/FTC or ABC/3TC. SINGLE randomised participants to DTG 50 mg+ABC/3TC QD or TDF/FTC/EFV (Atripla QD. In SPRING-2, changes in serum creatinine were examined by INI and NRTI backbone. Results: The two studies randomized and treated 1655 subjects, of whom 249 (15% were female, 388 (23% non-white, 495 (30% had HIV-1 RNA >100,000 c/ml, and 224 (14% had CD4+ count <200 cells/mm3. Primary analyses demonstrated non-inferiority of DTG to RAL in SPRING-2 (Δ=2.5%; 95% CI:−2.2% to +7.1%, excluding −10%, and superiority of the DTG regimen in SINGLE (7.4%; +2.5% to +12.3%. In SPRING-2, response rates by NRTI backbone were comparable in each viral load stratum. In SINGLE, a 7% difference in response (favoring DTG+ABC/3TC was observed in each viral load stratum. Exploratory analyses examining time-to-virologic failure showed no difference in response rates between the NRTIs irrespective of baseline viral load or study. Resistance to INIs or NRTIs was not demonstrated in any subject on DTG-based therapy through 48 weeks. Withdrawals due to AEs on DTG-based regimen were few (2% in both studies. In SPRING-2, no significant differences were observed in serum creatinine change from baseline to Week 48 by NRTI backbones. Conclusions: In SPRING-2 and SINGLE, DTG was effective with both ABC/3TC and TDF/FTC, and in subjects with high and low viral load. DTG was well tolerated in both studies. Renal safety also was similar by NRTI backbone. DTG is a once

  16. The influence of baseline marijuana use on treatment of cocaine dependence: application of an informative-priors Bayesian approach.

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    Charles eGreen

    2012-10-01

    Full Text Available Background: Marijuana use is prevalent among patients with cocaine dependence and often non-exclusionary in clinical trials of potential cocaine medications. The dual-focus of this study was to (1 examine the moderating effect of baseline marijuana use on response to treatment with levodopa/carbidopa for cocaine dependence; and (2 apply an informative-priors, Bayesian approach for estimating the probability of a subgroup-by-treatment interaction effect.Method: A secondary data analysis of two previously published, double-blind, randomized controlled trials provided samples for the historical dataset (Study 1: N = 64 complete observations and current dataset (Study 2: N = 113 complete observations. Negative binomial regression evaluated Treatment Effectiveness Scores (TES as a function of medication condition (levodopa/carbidopa, placebo, baseline marijuana use (days in past 30, and their interaction. Results: Bayesian analysis indicated that there was a 96% chance that baseline marijuana use predicts differential response to treatment with levodopa/carbidopa. Simple effects indicated that among participants receiving levodopa/carbidopa the probability that baseline marijuana confers harm in terms of reducing TES was 0.981; whereas the probability that marijuana confers harm within the placebo condition was 0.163. For every additional day of marijuana use reported at baseline, participants in the levodopa/carbidopa condition demonstrated a 5.4% decrease in TES; while participants in the placebo condition demonstrated a 4.9% increase in TES.Conclusion: The potential moderating effect of marijuana on cocaine treatment response should be considered in future trial designs. Applying Bayesian subgroup analysis proved informative in characterizing this patient-treatment interaction effect.

  17. Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Anxiety in Children : A Multiple Baseline Design Analysis

    Science.gov (United States)

    Jarrett, Matthew A.; Ollendick, Thomas H.

    2012-01-01

    Objective: The present study evaluated a 10-week psychosocial treatment designed specifically for children with attention-deficit/hyperactivity disorder (ADHD) and a comorbid anxiety disorder. Method: Using a nonconcurrent multiple baseline design, the authors treated 8 children ages 8-12 with ADHD, combined type, and at least 1 of 3 major anxiety…

  18. Initial evaluation of an integrated treatment for comorbid PTSD and smoking using a nonconcurrent, multiple-baseline design.

    Science.gov (United States)

    Feldner, Matthew T; Smith, Rose C; Monson, Candice M; Zvolensky, Michael J

    2013-09-01

    The present study examined an integrated treatment for comorbid posttraumatic stress disorder (PTSD) and smoking entitled "Smoke-Free to Overcome PTSD: An Integrated Treatment" (STOP IT program). A nonconcurrent multiple-baseline design was used with six community-recruited adult smokers with PTSD to investigate both patient acceptance of the treatment and its initial efficacy on both PTSD and smoking. Potential order effects of exposure-based and affect management components were also examined. A gold-standard assessment strategy that included the Clinician Administered PTSD Scale (Blake et al., 1995) and biochemical verification of self-reported smoking status was employed to measure primary targets of treatment. Results suggested that the STOP IT program was well tolerated. There were clinically significant improvements in PTSD outcomes, but only temporary reductions in smoking. Participants' relatively low posttreatment smoking levels increased by the follow-up assessment, although not to baseline levels. Treatment component order did not appear to affect treatment outcomes, but those who were assigned to the exposure-focused writing prior to affect management training condition appeared more likely to discontinue treatment before beginning exposure. These preliminary data support the safety, acceptability, and potential efficacy of the STOP IT program. Future investigation of the STOP IT program should include testing the incremental efficacy of increasing the dose of smoking-focused intervention, as well as randomized controlled tests of the treatment that employ gold standards for treatment outcome research.

  19. Low-dose budesonide treatment reduces severe asthma-related events in patients with infrequent asthma symptoms at baseline

    DEFF Research Database (Denmark)

    Reddel, H. K.; Busse, W. W.; Pedersen, Søren

    2015-01-01

    RATIONALE: Inhaled corticosteroids (ICS) are highly effective in low doses for reducing asthma-related exacerbation risk and mortality. Previously, ICS treatment was recommended for patients with 'persistent' asthma, defined by symptoms >2 days/week.1 However, for patients with less frequent...... symptoms, evidence is lacking for the benefit of ICS and safety of bronchodilator-only treatment. We investigated asthma outcomes by baseline symptom frequency in a post-hoc analysis of the multinational inhaled Steroid Treatment As Regular Therapy in early asthma (START) study.2 METHODS: Patients aged 4...

  20. Rorschach Inkblot Method data at baseline and after 2 years treatment of consecutively admitted patients with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Rosenbaum, Bent; Andersen, Palle Bent; Knudsen, Per Bjerregaard;

    2012-01-01

    Background: The Rorschach Inkblot Method is regarded as an important clinical instrument for detailed diagnostic description of the integrative capacities of individuals in psychotic states and as an instrument for measuring progression in the course of treatment. Aims: To describe relevant...... Rorschach variables at baseline in a group of consecutively admitted patients with first-episode schizophrenia. Furthermore, to describe the changes in these variables from baseline to year 2 for the group of patients given psychiatric standard treatment, and to compare these changes with changes in other......'s Rorschach Comprehensive System at inclusion and after 2 years. Results: Core variables of the Rorschach, assumed to show changes (e.g. reality testing, perceptual and thought disorders) in patients with a first episode of schizophrenia, all improved but revealed no significant changes after 2 years...

  1. Improvements in access to malaria treatment in Tanzania after switch to artemisinin combination therapy and the introduction of accredited drug dispensing outlets - a provider perspective

    Directory of Open Access Journals (Sweden)

    Dillip Angel

    2010-06-01

    Full Text Available Abstract Background To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP to artemether-lumefantrine (ALu in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania. Methods The study was carried out in the villages of Kilombero and Ulanga Demographic Surveillance System (DSS and in Ifakara town. Data collection consisted of: 1 yearly censuses of shops selling drugs; 2 collection of monthly data on availability of anti-malarials in public health facilities; and 3 retail audits to measure anti-malarial sales volumes in all public, mission and private outlets. The data were complemented with DSS population data. Results Between 2004 and 2008 access to malaria treatment greatly improved and the number of anti-malarial treatment doses dispensed increased by 78%. Particular improvements were observed in the availability (from 0.24 shops per 1,000 people in 2004 to 0.39 in 2008 and accessibility (from 71% of households within 5 km of a shop in 2004 to 87% in 2008 of drug shops. Despite no improvements in affordability this resulted in an increase of the market share from 49% of anti-malarial sales 2005 to 59% in 2008. The change of treatment policy from SP to ALu led to severe stock-outs of SP in health facilities in the months leading up to the introduction of ALu (only 40% months in stock, but these were compensated by the wide availability of SP in shops. After the introduction of ALu stock levels of the drug were relatively high in public health facilities (over 80% months in stock, but the drug could only be found in 30% of drug shops and in no general shops. This resulted in a low overall utilization of the drug (19% of all anti-malarial

  2. Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin

    Directory of Open Access Journals (Sweden)

    Mombo-Ngoma Ghyslain

    2010-10-01

    Full Text Available Abstract Background Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. Methods In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. Results SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. Conclusion These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed.

  3. Impact of medical treatment on lung diffusion capacity in elderly patients with heart failure. Baseline characteristics and 1-year follow up after medical treatment

    DEFF Research Database (Denmark)

    Petersen, Claus Leth; Kjaer, Andreas

    2005-01-01

    AIM: The aim of this investigation was (1) to study the effect of untreated chronic heart failure (CHF) on alveolar membrane diffusion capacity (transfer coefficient, K(CO)) in elderly patients and (2) to study the impact of the standard regime of medical treatment with diuretics and ACE-inhibito......AIM: The aim of this investigation was (1) to study the effect of untreated chronic heart failure (CHF) on alveolar membrane diffusion capacity (transfer coefficient, K(CO)) in elderly patients and (2) to study the impact of the standard regime of medical treatment with diuretics and ACE...... treatment (baseline) and after 1 year of treatment with diuretics and ACE-inhibitors/angiotensin-II receptor antagonists. Age- and gender-matched healthy volunteers were included as control group. RESULTS: (mean+/-S.E.M.): K(CO) at baseline was 0.95+/-0.06 and 1.25+/-0.04 mmol/min x kPa/l in HF patients...

  4. The effect of support on internet-delivered treatment for Insomnia : Does baseline depression severity matter?

    NARCIS (Netherlands)

    Lancee, Jaap; Sorbi, Marjolijn J.; Eisma, Maarten C.; van Straten, Annemieke; van den Bout, Jan

    2014-01-01

    Internet-delivered cognitive-behavioral treatment is effective for insomnia. However, little is known about the beneficial effects of support. Recently we demonstrated that motivational support moderately improved the effects of Internet-delivered treatment for insomnia. In the present study, we tes

  5. The effect of support on Internet-delivered treatment for insomnia: Does baseline depression severity matter?

    NARCIS (Netherlands)

    Lancee, J.; Sorbi, M.J.; Eisma, M.C.; van Straten, A.; van den Bout, J.

    2014-01-01

    Internet-delivered cognitive-behavioral treatment is effective for insomnia. However, little is known about the beneficial effects of support. Recently we demonstrated that motivational support moderately improved the effects of Internet-delivered treatment for insomnia. In the present study, we tes

  6. Quality of life after prostate cancer treatments in patients comparable at baseline

    NARCIS (Netherlands)

    Tol-Geerdink, J.J. van; Leer, J.W.H.; Oort, I.M. van; Lin, E.J. van; Weijerman, P.C.; Vergunst, H.; Witjes, J.A.; Stalmeier, P.F.M.

    2013-01-01

    Background:Previous studies on the effects of different prostate cancer treatments on quality of life, were confounded because patients were not comparable. This study examined treatment effects in more comparable groups.Methods:From 2008-2011, 240 patients with localised prostate cancer were select

  7. Baseline depression severity as a predictor of single and combination antidepressant treatment outcome: Results from the CO-MED Trial

    Science.gov (United States)

    Friedman, Edward S.; Davis, Lori L.; Zisook, Sidney; Wisniewski, Stephen R.; Trivedi, Madhukar H.; Fava, Maurizio; Rush, A. John

    2011-01-01

    The objective of this manuscript is to report associations between baseline depressive severity and (1) baseline sociodemographic and clinical characteristics, (2) treatment outcomes, and (3) differential outcomes for three treatment groups. Six hundred and sixty-five outpatients with nonpsychotic, major depressive disorder were prospectively randomized to treatment with either a selective serotonin reuptake inhibitor (SSRI) monotherapy (escitalopram plus placebo) or one of two antidepressant medication combinations (bupropion-sustained release plus escitalopram, or venlafaxine-extended release plus mirtazapine). For purposes of these analyses, participants were divided into four groups based on baseline severity by the 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) total score: mild (0–10) [N=81], moderate (11–15) [N=238], severe (16–20) [N=260] and very severe (21–27) [N=67]. Treatment outcomes at 12 and 28 weeks were compared among the four severity groups. A history of childhood neglect and/or abuse was strongly associated with the severity of adult depression (1/2 of participants in the very severy group versus 1/5–1/4 of those in the mild group reported abuse and/or neglect). The degree of suicidality (e.g., 15/.4% of the very severe group ever attempted suicide versus none in the mild group), the number of suicide attempts (e.g., mean of .41 +/− 1.99 suicide attempts in the severe group versus o.o +/−0.0 in the mild group) and severity of suicidality (e.g., 9.2% of participants in very severe group had a plan or made a gesture versus 5.6% in moderate group and none in the mild group) were increased in more severe groups. Participants with a greater baseline depressive severity reported significantly more psychiatric comorbitities (e..g. [at p < 0.05] increased rates of agoraphobia, bulimia, generalized anxiety, hypocondriasis, panic disorder, post-traumatic stress disorder, social phobia and somatoform disorder

  8. ASPEN computer simulations of the mixed waste treatment project baseline flowsheet

    Energy Technology Data Exchange (ETDEWEB)

    Dietsche, L.J.; Upadhye, R.S.; Camp, D.W.; Pendergrass, J.A.; Borduin, L.C.; Thompson, T.K.

    1994-07-05

    The treatment and disposal of mixed waste (i.e., waste containing both hazardous and radioactive components) is a challenging waste- management problem of particular concern to Department of Energy (DOE) sites throughout the United States. Traditional technologies used for destroying hazardous wastes must be re- evaluated for their ability to handle mixed wastes, and, in some cases, new technologies must be developed. The Mixed Waste Treatment Project (MWTP), a collaborative effort between Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory, and Pacific Northwest Laboratory (PNL), was established by the DOE`s Waste Operations Program (EM-30) to develop and analyze alternative mixed waste treatment approaches. One of the MWTP`s initiatives, and the objective of this study, was to develop flowsheets for prototype, integrated, mixed-waste treatment facilities that can serve as models for sites developing their own treatment strategies. Evaluation of these flowsheets is being facilitated through the use of computer modeling. The objectives of the flowsheet simulations are to compare process effectiveness and costs of alternative flowsheets and to determine if commercial process-simulation software could be used on the large, complex process of an integrated mixed waste processing facility. Flowsheet modeling is needed to evaluate many aspects of proposed flowsheet designs. A major advantage of modeling the complete flowsheet is the ability to define the internal recycle streams, thereby making it possible to evaluate the impact of one operation on the whole plant. Many effects that can be seen only in this way. Modeling also can be used to evaluate sensitivity and range of operating conditions, radioactive criticality, and relative costs of different flowsheet designs. Further, the modeled flowsheets must be easily modified so that one can examine how alternative technologies and varying feed streams affect the overall integrated process.

  9. Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

    Science.gov (United States)

    Grimm, Richard H.; Margolis, Karen L.; Papademetriou, Vasilios; Cushman, William C.; Ford, Charles E.; Bettencourt, Judy; Alderman, Michael H.; Basile, Jan N.; Black, Henry R.; DeQuattro, Vincent; Eckfeldt, John; Hawkins, C. Morton; Perry, H. Mitchell; Proschan, Michael

    2001-01-01

    -Diuretics and ss-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and alpha-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged >/=55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged >/=70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics?

  10. Baseline study of methane emission from anaerobic ponds of palm oil mill effluent treatment.

    Science.gov (United States)

    Yacob, Shahrakbah; Ali Hassan, Mohd; Shirai, Yoshihito; Wakisaka, Minato; Subash, Sunderaj

    2006-07-31

    The world currently obtains its energy from the fossil fuels such as oil, natural gas and coal. However, the international crisis in the Middle East, rapid depletion of fossil fuel reserves as well as climate change have driven the world towards renewable energy sources which are abundant, untapped and environmentally friendly. Malaysia has abundant biomass resources generated from the agricultural industry particularly the large commodity, palm oil. This paper will focus on palm oil mill effluent (POME) as the source of renewable energy from the generation of methane and establish the current methane emission from the anaerobic treatment facility. The emission was measured from two anaerobic ponds in Felda Serting Palm Oil Mill for 52 weeks. The results showed that the methane content was between 35.0% and 70.0% and biogas flow rate ranged between 0.5 and 2.4 L/min/m(2). Total methane emission per anaerobic pond was 1043.1 kg/day. The total methane emission calculated from the two equations derived from relationships between methane emission and total carbon removal and POME discharged were comparable with field measurement. This study also revealed that anaerobic pond system is more efficient than open digesting tank system for POME treatment. Two main factors affecting the methane emission were mill activities and oil palm seasonal cropping.

  11. Baseline study of methane emission from open digesting tanks of palm oil mill effluent treatment.

    Science.gov (United States)

    Yacob, Shahrakbah; Hassan, Mohd Ali; Shirai, Yoshihito; Wakisaka, Minato; Subash, Sunderaj

    2005-06-01

    Anthropogenic release of greenhouse gases, especially CO2 and CH4 has been recognized as one of the main causes of global warming. Several measures under the Kyoto Protocol 1997 have been drawn up to reduce the greenhouse gases emission. One of the measures is Clean Development Mechanisms (CDM) that was created to enable developed countries to cooperate with developing countries in emission reduction activities. In Malaysia, palm oil industry particularly from palm oil mill effluent (POME) anaerobic treatment has been identified as an important source of CH4. However, there is no study to quantify the actual CH4 emission from the commercial scale wastewater treatment facility. Hence, this paper shall address the CH4 emission from the open digesting tanks in Felda Serting Hilir Palm Oil Mill. CH4 emission pattern was recorded for 52 weeks from 3600 m3 open digesting tanks. The findings indicated that the CH4 content was between 13.5% and 49.0% which was lower than the value of 65% reported earlier. The biogas flow rate ranged between 0.8l min(-1)m(-2) and 9.8l min(-1)m(-2). Total CH4 emission per open digesting tank was 518.9 kgday(-1). Relationships between CH4 emission and total carbon removal and POME discharged were also discussed. Fluctuation of biogas production was observed throughout the studies as a result of seasonal oil palm cropping, mill activities, variation of POME quality and quantity discharged from the mill. Thus only through long-term field measurement CH4 emission can be accurately estimated.

  12. Can persons with a history of multiple addiction treatment episodes benefit from technology delivered behavior therapy? A moderating role of treatment history at baseline.

    Science.gov (United States)

    Kim, Sunny Jung; Marsch, Lisa A; Acosta, Michelle C; Guarino, Honoria; Aponte-Melendez, Yesenia

    2016-03-01

    A growing line of research has shown positive treatment outcomes from technology-based therapy for substance use disorders (SUDs). However, little is known about the effectiveness of technology-based SUD interventions for persons who already had numerous prior SUD treatments. We conducted a secondary analysis on a 12-month trial with patients (N=160) entering methadone maintenance treatment (MMT). Patients were randomly assigned to either standard MMT treatment or a model in which half of standard counseling sessions were replaced with a computer-based intervention, called Therapeutic Education System (standard+TES). Four treatment history factors at baseline, the number of lifetime SUD treatment episodes, detoxification episodes, and inpatient/outpatient treatment episodes were categorized into three levels based on their tertile points, and analyzed as moderators. Dependent variables were urine toxicology results for opioid and cocaine abstinence for 52-weeks. The standard+TES condition produced significantly better opioid abstinence than standard treatment for participants with 1) a moderate or high frequency of lifetime SUD treatment episodes, and 2) those with all three levels (low, moderate and high) of detoxification and inpatient/outpatient treatment episodes, pshistory, pstechnology-based behavioral therapy as part of treatment can be more effective than MMT alone, even among patients with a history of multiple addiction treatment episodes.

  13. Baseline Flowsheet Generation for the Treatment and Disposal of Idaho National Engineering and Environmental Laboratory Sodium Bearing Waste

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, C.M.; Lauerhass, L.; Olson, A.L.; Taylor, D.D.; Valentine, J.H.; Lockie, K.A. (DOE- ID)

    2002-01-16

    The High-Level Waste (HLW) Program at the Idaho National Engineering and Environmental Laboratory (INEEL) must implement technologies and processes to treat and qualify radioactive wastes located at the Idaho Nuclear Technology and Engineering Center (INTEC) for permanent disposal. This paper describes the approach and accomplishments to date for completing development of a baseline vitrification treatment flowsheet for sodium-bearing waste (SBW), including development of a relational database used to manage the associated process assumptions. A process baseline has been developed that includes process requirements, basis and assumptions, process flow diagrams, a process description, and a mass balance. In the absence of actual process or experimental results, mass and energy balance data for certain process steps are based on assumptions. Identification, documentation, validation, and overall management of the flowsheet assumptions are critical to ensuring an integrated, focused program. The INEEL HLW Program initially used a roadmapping methodology, developed through the INEEL Environmental Management Integration Program, to identify, document, and assess the uncertainty and risk associated with the SBW flowsheet process assumptions. However, the mass balance assumptions, process configuration and requirements should be accessible to all program participants. This need resulted in the creation of a relational database that provides formal documentation and tracking of the programmatic uncertainties related to the SBW flowsheet.

  14. Baseline Flowsheet Generation for the Treatment and Disposal of Idaho National Engineering and Environmental Laboratory Sodium Bearing Waste

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, Charles Marshall; Lauerhass, Lance; Olson, Arlin Leland; Taylor, Dean Dalton; Valentine, James Henry; Lockie, Keith Andrew

    2002-02-01

    The High-Level Waste (HLW) Program at the Idaho National Engineering and Environmental Laboratory (INEEL) must implement technologies and processes to treat and qualify radioactive wastes located at the Idaho Nuclear Technology and Engineering Center (INTEC) for permanent disposal. This paper describes the approach and accomplishments to date for completing development of a baseline vitrification treatment flowsheet for sodium-bearing waste (SBW), including development of a relational database used to manage the associated process assumptions. A process baseline has been developed that includes process requirements, basis and assumptions, process flow diagrams, a process description, and a mass balance. In the absence of actual process or experimental results, mass and energy balance data for certain process steps are based on assumptions. Identification, documentation, validation, and overall management of the flowsheet assumptions are critical to ensuring an integrated, focused program. The INEEL HLW Program initially used a roadmapping methodology, developed through the INEEL Environmental Management Integration Program, to identify, document, and assess the uncertainty and risk associated with the SBW flowsheet process assumptions. However, the mass balance assumptions, process configuration and requirements should be accessible to all program participants. This need resulted in the creation of a relational database that provides formal documentation and tracking of the programmatic uncertainties related to the SBW flowsheet.

  15. Cluster-randomized study of intermittent preventive treatment for malaria in infants (IPTi in southern Tanzania: evaluation of impact on survival

    Directory of Open Access Journals (Sweden)

    Schellenberg Joanna

    2011-12-01

    Full Text Available Abstract Background Intermittent Preventive Treatment for malaria control in infants (IPTi consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204]. Methods After baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12 or not (n = 12. Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived. Results Survival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P P = 0.31. Conclusion The lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.

  16. Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K.; Lal, Sham; Cundill, Bonnie;

    2013-01-01

    BACKGROUND: Since drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial...... shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received. RESULTS: Among febrile...

  17. Prediction of long-term metabolic effects of olanzapine and risperidone treatment from baseline body mass index in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Bobo, William Victor; Bonaccorso, Stefania; Jayathilake, Karuna; Meltzer, Herbert Yale

    2011-09-30

    Baseline body mass index (BMI), baseline BMI status (normal, overweight, obese) and early (1 month) BMI increases were tested as predictors of 6- and 12-month increases in glucose and lipid measures in 82 olanzapine (OLZ)- and 78 risperidone (RIS)-treated patients with schizophrenia, schizoaffective disorder, or bipolar disorder who participated in a 12-month randomized, prospective metabolic effects study. Baseline BMI predicted greater fasting glucose and HgbA1c levels at 12 months for both treatments. Early BMI change predicted fasting glucose levels at 6 months, but not HgbA1c or BMI, at either time point. For patients who received no concomitant mood stabilizers, early BMI change predicted 12 month HgbA1c values in the OLZ group, and 6- (but not 12-) month fasting glucose and HgbA1c values in the RIS group. Neither baseline BMI nor early BMI change consistently predicted increases in lipids with either drug. OLZ-treated patients with normal baseline BMI had greater increases in total cholesterol, triglycerides, and non-HDL-cholesterol than those who were overweight or obese. In conclusion, higher baseline BMI predicted adverse glycemic changes after 12 months with OLZ and RIS. Individuals with normal baseline BMI may be most susceptible to OLZ-induced hyperlipidosis. Frequency of metabolic screening should be independent of baseline BMI or rapid increases in BMI.

  18. Variation in pre-treatment count lead time and its effect on baseline estimates of cage-level sea lice abundance.

    Science.gov (United States)

    Gautam, R; Boerlage, A S; Vanderstichel, R; Revie, C W; Hammell, K L

    2016-11-01

    Treatment efficacy studies typically use pre-treatment sea lice abundance as the baseline. However, the pre-treatment counting window often varies from the day of treatment to several days before treatment. We assessed the effect of lead time on baseline estimates, using historical data (2010-14) from a sea lice data management programme (Fish-iTrends). Data were aggregated at the cage level for three life stages: (i) chalimus, (ii) pre-adult and adult male and (iii) adult female. Sea lice counts were log-transformed, and mean counts by lead time relative to treatment day were computed and compared separately for each life stage, using linear mixed models. There were 1,658 observations (treatment events) from 56 sites in 5 Bay Management Areas. Our study showed that lead time had a significant effect on the estimated sea lice abundance, which was moderated by season. During the late summer and autumn periods, counting on the day of treatment gave significantly higher values than other days and would be a more appropriate baseline estimate, while during spring and early summer abundance estimates were comparable among counts within 5 days of treatment. A season-based lead time window may be most appropriate when estimating baseline sea lice levels.

  19. Pattern of drug utilization for treatment of uncomplicated malaria in urban Ghana following national treatment policy change to artemisinin-combination therapy

    Directory of Open Access Journals (Sweden)

    Tenkorang Ofori

    2009-01-01

    Full Text Available Abstract Background Change of first-line treatment of uncomplicated malaria to artemisinin-combination therapy (ACT is widespread in Africa. To expand knowledge of safety profiles of ACT, pharmacovigilance activities are included in the implementation process of therapy changes. Ghana implemented first-line therapy of artesunate-amodiaquine in 2005. Drug utilization data is an important component of determining drug safety, and this paper describes how anti-malarials were prescribed within a prospective pharmacovigilance study in Ghana following anti-malarial treatment policy change. Methods Patients with diagnosis of uncomplicated malaria were recruited from pharmacies of health facilities throughout Accra in a cohort-event monitoring study. The main drug utilization outcomes were the relation of patient age, gender, type of facility attended, mode of diagnosis and concomitant treatments to the anti-malarial regimen prescribed. Logistic regression was used to predict prescription of nationally recommended first-line therapy and concomitant prescription of antibiotics. Results The cohort comprised 2,831 patients. Curative regimens containing an artemisinin derivative were given to 90.8% (n = 2,574 of patients, although 33% (n = 936 of patients received an artemisinin-based monotherapy. Predictors of first-line therapy were laboratory-confirmed diagnosis, age >5 years, and attending a government facility. Analgesics and antibiotics were the most commonly prescribed concomitant medications, with a median of two co-prescriptions per patient (range 1–9. Patients above 12 years were significantly less likely to have antibiotics co-prescribed than patients under five years; those prescribed non-artemisinin monotherapies were more likely to receive antibiotics. A dihydroartemisinin-amodiaquine combination was the most used therapy for children under five years of age (29.0%, n = 177. Conclusion This study shows that though first-line therapy

  20. Diabetes treatment patterns and goal achievement in primary diabetes care (DiaRegis - study protocol and patient characteristics at baseline

    Directory of Open Access Journals (Sweden)

    Deeg Evelin

    2010-09-01

    Full Text Available Abstract Background Patients with type 2 diabetes are at an increased risk for disease and treatment related complications after the initial approach of oral mono/dual antidiabetic therapy has failed. Data from clinical practice with respect to this patient group are however scarce. Therefore we set up a registry in primary care documenting the course and outcomes of this patient group. Methods Diabetes Treatment Patterns and Goal Achievement in Primary Diabetes Care (DiaRegis is a prospective, observational, German, multicenter registry including patients with type-2 diabetes in which oral mono/dual antidiabetic therapy has failed. Data were recorded at baseline and will be prospectively documented during visits at 6 ± 1, 12 ± 2 and 24 ± 2 months. The primary objective is to estimate the proportion of patients with at least 1 episode of severe hypoglycemia within one year. Results 313 primary care offices included 4,048 patients between June 2009 and March 2010 of which 3,810 patients fulfilled the in- and exclusion criteria. 46.7% of patients were female; patients had a median diabetes duration of 5.5 years and most were obese with respect to BMI or waist circumference. HbA1c at baseline was 7.4%, fasting plasma glucose 142 mg/dl and postprandial glucose 185 mg/dl. Co-morbidity in this patient population was substantial with 17.9% having coronary artery disease, 14.4% peripheral neuropathy, 9.9% heart failure and 6.0% peripheral arterial disease. 68.6% of patients received oral monotherapy, 31.4% dual oral combination therapy. The most frequent antidiabetic agent used as monotherapy was metformin (79.0% followed by sulfonylureas (14.8%. Conclusions DiaRegis is a large, prospective registry in primary diabetes care to document the course and outcomes of patients with type-2 diabetes in which the initial approach of oral mono/dual antidiabetic therapy has failed. The two year follow-up will allow for a prospective evaluation of these patients

  1. ADVANCES IN THE TREATMENT OF MALARIA

    Directory of Open Access Journals (Sweden)

    Francesco Castelli

    2012-10-01

    Full Text Available Malaria still claims a heavy toll of deaths and disabilities even at the beginning of the third millennium. The inappropriate sequential use of drug monotherapy in the past has facilitated the spread of drug-resistant P. falciparum, and to a lesser extend P. vivax, strains in most of the malaria endemic areas, rendering most anti-malarial ineffective. In the last decade, a new combination strategy based on artemisinin derivatives (ACT has become the standard of treatment for most P. falciparum malaria infections. This strategy could prevent the selection of resistant strains by rapidly decreasing the parasitic burden (by the artemisinin derivative, mostly artesunate and exposing the residual parasite to effective concentrations of the partner drug. The widespread use of this strategy is somehow constrained by cost and by the inappropriate use of artemisinin, with possible impact on resistance, as already sporadically observed in South East Asia. Parenteral artesunate has now become the standard of care for severe malaria, even if quinine still retains its value in case artesunate is not immediately available. The appropriateness of pre-referral use of suppository artesunate is under close monitoring, while waiting for an effective anti-malarial vaccine to be made available.

  2. ADVANCES IN THE TREATMENT OF MALARIA

    Directory of Open Access Journals (Sweden)

    Francesco Castelli

    2012-01-01

    Full Text Available

    Malaria still claims a heavy toll of deaths and disabilities even at the beginning of the third millennium. The inappropriate sequential use of drug monotherapy in the past has facilitated the spread of drug-resistant P. falciparum, and to a lesser extend P. vivax, strains in most of the malaria endemic areas, rendering most anti-malarial ineffective. In the last decade, a new combination strategy based on artemisinin derivatives (ACT has become the standard of treatment for most P. falciparum malaria infections. This strategy could prevent the selection of resistant strains by rapidly decreasing the parasitic burden (by the artemisinin derivative, mostly artesunate and exposing the residual parasite to effective concentrations of the partner drug. The widespread use of this strategy is somehow constrained by cost and by the inappropriate use of artemisinin, with possible impact on resistance, as already sporadically observed in South East Asia. Parenteral artesunate has now become the standard of care for severe malaria, even if quinine still retains its value in case artesunate is not immediately available. The appropriateness of pre-referral use of suppository artesunate is under close monitoring, while waiting for an effective anti-malarial vaccine to be made available.

  3. Treatment of imported severe malaria with artesunate instead of quinine - more evidence needed?

    Directory of Open Access Journals (Sweden)

    Grobusch Martin P

    2011-09-01

    Full Text Available Abstract Rapid and fast acting anti-malarials are essential to treat severe malaria. Quinine has been the only option for parenteral therapy until recently. While current evidence shows that intravenous artesunate is more effective than quinine in treating severe malaria in endemic countries, some questions remain regarding safety profiles and drug resistance. For imported severe malaria, additional unanswered questions are related to generalizability of the findings from endemic countries and to legal aspects, as there is no Good Manufacturing Practice-conform drug available yet. Here, the implications of existing evidence for the treatment of imported severe malaria are discussed.

  4. Three-year follow-up of ranibizumab treatment of wet age-related macular degeneration: influence of baseline visual acuity and injection frequency on visual outcomes

    Directory of Open Access Journals (Sweden)

    Razi F

    2016-02-01

    Full Text Available Faraz Razi,1 Adnaan Haq,2 Prabhu Tonne,3 Maharatnam Logendran3 1Department of Paediatrics, Basingstoke and North Hampshire Hospital, Basingstoke, UK; 2Department of Ophthalmology, Leicester General Hospital, Leicester, UK; 3Department of Ophthalmology, Northampton General Hospital, Northampton, UK Purpose: To determine the effect of ranibizumab on visual acuity (VA following a 3-year treatment period for patients diagnosed with wet age-related macular degeneration. To establish whether baseline VA and injection frequency influence visual outcomes. Patients and methods: Retrospective review of 70 patients (76 eyes treated with 0.5 mg intravitreal ranibizumab for 3 consecutive months, and pro re nata thereafter (three + pro re nata protocol, over a 3-year period. VA was measured using Early Treatment Diabetic Retinopathy Study (ETDRS charts at baseline, 12, 24, and 36 months. The number of injections administered at the end of years 1, 2, and 3 were also recorded. Eyes were stratified according to baseline VA, as well as the number of injections administered at the end of year 1. Linear regression analysis determined the relationship between VA and both baseline VA and injection frequency. P<0.05 was considered statistically significant. Results: At 36 months, VA improved by a mean of 5.3 ETDRS letters (P=0.002, with 29% of eyes (n=22 demonstrating a clinically significant improvement in VA (gain of ≥15 ETDRS letters. Improvements in VA from baseline to 36 months were inversely proportional to the baseline VA (R=0.414, P=<0.001. A positive correlation was observed between injection frequency and change in VA from baseline to 36 months (R=0.244, P=0.036. Conclusion: Mean improvement in VA is inversely proportional to baseline VA, and directly proportional to injection frequency. Keywords: long-term results, Lucentis, neovascular AMD

  5. Depression CBT treatment gains among HIV-infected persons with a history of injection drug use varies as a function of baseline substance use.

    Science.gov (United States)

    Labbe, Allison K; O'Cleirigh, Conall M; Stein, Michael; Safren, Steven A

    2015-01-01

    Depression and substance use, the most common comorbidities with HIV, are both associated with poor treatment outcomes and accelerated HIV disease progression. Though previous research has demonstrated short-term and follow-up success for cognitive behavioral therapy for adherence and depression (CBT-AD) on depression outcomes among patients with HIV in care and among patients with HIV in active substance abuse treatment for injection drug use (IDU), there is little information regarding possible moderating effects of active use versus abstinence on depression treatment gains. The present study aimed to examine recent substance use at treatment initiation as a moderator of the acute and maintenance effects of CBT-AD on depression. We used data from a two-arm, randomized controlled trial (N = 89) comparing CBT-AD to enhanced treatment as usual in individuals in treatment for IDU. To test whether depression at time of presentation affected outcomes, repeated-measures ANOVAs were conducted for two time frames: (1) acute phase (baseline to post-treatment) (acute) and (2) maintenance phase (baseline to 12-month follow-up). To further examine maintenance of gains, we additionally looked at post-treatment to 12-month follow-up. Depression scores derived from the clinical global impression for severity and the Montgomery-Asberg depression rating scale (MADRS) served as the primary outcome variables. Acute (baseline post treatment) moderation effects were found for those patients endorsing active drug use at baseline in the CBT-AD condition, who demonstrated the greatest reductions in MADRS scores at post-treatment (F[1,76] = 6.78, p = .01) and follow-up (F[1,61] = 5.46, p = .023). Baseline substance use did not moderate differences from post-treatment to 12-month follow-up as depression treatment gains that occurred acutely from baseline to post-treatment were maintained across both patients engaged in substance use and abstainers. We conclude that CBT

  6. Diversity oriented synthesis for novel anti-malarials.

    Science.gov (United States)

    Bathula, Chandramohan; Singh, Shailja; Sen, Subhabrata

    2015-12-01

    Malaria a global pandemic has engulfed nearly 0.63 million people globally. It is high time that a cure for malaria is required to stop its ever increasing menace. Our commentary discusses the advent and contribution of diversity oriented synthesis (DOS) in the drug discovery efforts towards developing cure for malaria. DOS based on chemical genetics focusses on design and synthesis of molecular libraries which covers large tracts of biologically relevant chemical space. Herein we will discuss the applications, advantages, disadvantages and future directions of DOS with respect to malaria.

  7. Malaria prevention and treatment in pregnancy: survey of current practice among private medical practitioners in Lagos, Nigeria.

    Science.gov (United States)

    Rabiu, Kabiru Afolarin; Davies, Nosimot Omolola; Nzeribe-Abangwu, Ugochi O; Adewunmi, Adeniyi Abiodun; Akinlusi, Fatimat Motunrayo; Akinola, Oluwarotimi Ireti; Ogundele, Sunday O

    2015-01-01

    We studied the practice of malaria prevention and treatment in pregnancy of 394 private medical practitioners in Lagos State, Nigeria using a self-administered pre-tested structured questionnaire. Only 39 (9.9%) respondents had correct knowledge of the World Health Organization (WHO) strategies. Malaria prophylaxis in pregnancy was offered by 336 (85.3%), but only 98 (24.9%) had correct knowledge of recommended chemoprophylaxis. Of these, 68 (17.3%) had correct knowledge of first trimester treatment, while only 41 (10.4%) had knowledge of second and third trimester treatment. Only 64 (16.2%) of respondents routinely recommended use of insecticide-treated bed nets. The most common anti-malarial drug prescribed for chemoprophylaxis was pyrimethamine (43.7%); chloroquine was the most common anti-malarial prescribed for both first trimester treatment (81.5%) and second and third trimester treatment (55.3%). The study showed that private medical practitioners have poor knowledge of malaria prophylaxis and treatment in pregnancy, and the practice of most do not conform to recommended guidelines.

  8. Low Baseline Interleukin-17A Levels Are Associated with Better Treatment Response at 12 Weeks to Tocilizumab Therapy in Rheumatoid Arthritis Patients

    Directory of Open Access Journals (Sweden)

    Sang Jin Lee

    2015-01-01

    Full Text Available T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ, a humanized monoclonal antibody against the interleukin- (IL- 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28 remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%, P=0.032. DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks (P=0.045 and 24 weeks (P=0.046 after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.

  9. Low baseline interleukin-17A levels are associated with better treatment response at 12 weeks to tocilizumab therapy in rheumatoid arthritis patients.

    Science.gov (United States)

    Lee, Sang Jin; Park, Won; Park, Sung Hwan; Shim, Seung-Cheol; Baek, Han Joo; Yoo, Dae-Hyun; Kim, Hyun Ah; Lee, Soo Kon; Leee, Yun Jong; Park, Young Eun; Cha, Hoon-Suk; Park, Jin Kyun; Lee, Eun Young; Lee, Eun Bong; Song, Yeong Wook

    2015-01-01

    T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin- (IL-) 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28) remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%, P = 0.032). DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks (P = 0.045) and 24 weeks (P = 0.046) after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.

  10. Sleep and cognition at baseline and the effects of REM sleep diminution after 1 week of antidepressive treatment in patients with depression.

    Science.gov (United States)

    Göder, Robert; Seeck-Hirschner, Mareen; Stingele, Karoline; Huchzermeier, Christian; Kropp, Cornelia; Palaschewski, Milena; Aldenhoff, Josef; Koch, Jakob

    2011-12-01

    It has been hypothesized that non-rapid eye movement (NREM) sleep facilitates declarative memory consolidation, and rapid eye movement (REM) sleep is particularly important in promoting procedural learning. The aim of this study was to examine the effects of pharmacological REM sleep suppression on performance in different neuropsychological tasks. For our baseline, we chose 41 moderately depressed patients (age range 19-44 years), who were not taking antidepressants. In the morning after polysomnography, we tested memory recall and cognitive flexibility by assessment of verbal and figural fluency, a shift of attention task and the Trail Making Test B. After recording baseline values, patients were assigned randomly to one of three treatment groups: medication with citalopram; medication with reboxetine; or exclusive treatment with psychotherapy. Retesting took place 1 week after onset of treatment. The main results were: (1) an association of slow-wave sleep with verbal memory performance at baseline; (2) a suppression of REM sleep in patients taking citalopram and reboxetine; (3) no differences regarding neuropsychological performance within the treatment groups; and (4) no association of REM sleep diminution with decreases in memory performance or cognitive flexibility in patients treated with citalopram or reboxetine. In line with other studies, our results suggest that there are no negative effects of a decrease in REM sleep on memory performance in patients taking antidepressants.

  11. Varying efficacy of artesunate+amodiaquine and artesunate+sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in the Democratic Republic of Congo: a report of two in-vivo studies

    Directory of Open Access Journals (Sweden)

    van Overmeir Chantal

    2009-08-01

    Full Text Available Abstract Background Very few data on anti-malarial efficacy are available from the Democratic Republic of Congo (DRC. DRC changed its anti-malarial treatment policy to amodiaquine (AQ and artesunate (AS in 2005. Methods The results of two in vivo efficacy studies, which tested AQ and sulphadoxine-pyrimethamine (SP monotherapies and AS+SP and AS+AQ combinations in Boende (Equatorial province, and AS+SP, AS+AQ and SP in Kabalo (Katanga province, between 2003 and 2004 are presented. The methodology followed the WHO 2003 protocol for assessing the efficacy of anti-malarials in areas of high transmission. Results Out of 394 included patients in Boende, the failure rates on day 28 after PCR-genotyping adjustment of AS+SP and AS+AQ were estimated as 24.6% [95% CI: 16.6–35.5] and 15.1% [95% CI: 8.6–25.7], respectively. For the monotherapies, failure rates were 35.9% [95% CI: 27.0–46.7] for SP and 18.3% [95% CI: 11.6–28.1] for AQ. Out of 207 patients enrolled in Kabalo, the failure rate on day 28 after PCR-genotyping adjustment was 0 [1-sided 95% CI: 5.8] for AS+SP and AS+AQ [1-sided 95% CI: 6.2]. It was 19.6% [95% CI: 11.4–32.7] for SP monotherapy. Conclusion The finding of varying efficacy of the same combinations at two sites in one country highlights one difficulty of implementing a uniform national treatment policy in a large country. The poor efficacy of AS+AQ in Boende should alert the national programme to foci of resistance and emphasizes the need for systems for the prospective monitoring of treatment efficacy at sentinel sites in the country.

  12. Regression to the mean and predictors of MRI disease activity in RRMS placebo cohorts--is there a place for baseline-to-treatment studies in MS?

    Directory of Open Access Journals (Sweden)

    Jan-Patrick Stellmann

    Full Text Available Gadolinium-enhancing (GD+ lesions and T2 lesions are MRI outcomes for phase-2 treatment trials in relapsing-remitting Multiple Sclerosis (RRMS. Little is known about predictors of lesion development and regression-to-the-mean, which is an important aspect in early baseline-to-treatment trials.To quantify regression-to-the-mean and identify predictors of MRI lesion development in placebo cohorts.21 Phase-2 and Phase-3 trials were identified by a systematic literature research. Random-effects meta-analyses were performed to estimate development of T2 and GD+ after 6 months (phase-2 or 2 years (phase-3. Predictors of lesion development were evaluated with mixed-effect meta-regression.The mean number of GD+-lesions per scan was similar after 6 months (1.19, 95%CI: 0.87-1.51 and 2 years (1.19, 95%CI: 1.00-1.39. 39% of the patients were without new T2-lesion after 6 month and 19% after 2 years (95%CI: 12-25%. Mean number of baseline GD+-lesions was the best predictor for new lesions after 6 months.Baseline GD-enhancing lesions predict evolution of Gd- and T2 lesions after 6 months and might be used to control for regression to the mean effects. Overall, proof-of-concept studies with a baseline to treatment design have to face a regression to 1.2 GD+lesions per scan within 6 months.

  13. Optimal price subsidies for appropriate malaria testing and treatment behaviour

    DEFF Research Database (Denmark)

    Hansen, K. S.; Lesner, T. H.; Østerdal, L. P.

    2016-01-01

    of presumptive diagnosis. A global subsidy on artemisinin-based combination therapy (ACT) has recently been suggested to increase access to the most effective malaria treatment. Methods: Following the recommendation by World Health Organization that parasitological testing should be performed before treatment......, ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced...... to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. Results: Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs...

  14. Surveillance of the efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum among children under five in Togo, 2005-2009

    Directory of Open Access Journals (Sweden)

    Dorkenoo Monique A

    2012-10-01

    Full Text Available Abstract Background Malaria remains a major public health problem in Togo. The national malaria control programme in Togo changed the anti-malarial treatment policy from monotherapy to artemisinin combination therapy in 2004. This study reports the results of therapeutic efficacy studies conducted on artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Togo, between 2005 and 2009. Methods Children between 6 and 59 months of age, who were symptomatically infected with P. falciparum, were treated with either artemether-lumefantrine or artesunate-amodiaquine. The primary end-point was the 28-day cure rate, PCR-corrected for reinfection and recrudescence. Studies were conducted according to the standardized WHO protocol for the assessment of the efficacy of anti-malarial treatment. Differences between categorical data were compared using the chi-square test or the Fisher’s exact test where cell counts were ≤ 5. Differences in continuous data were compared using a t-test. Results A total of 16 studies were conducted in five sentinel sites, with 459, 505 and 332 children included in 2005, 2007 and 2009, respectively. The PCR-corrected 28-day cure rates using the per-protocol analysis were between 96%-100% for artemether-lumefantrine and 94%-100% for artesunate-amodiaquine. Conclusions Both formulations of artemisinin-based combination therapy were effective over time and no severe adverse events related to the treatment were reported during the studies.

  15. Optimal price subsidies for appropriate malaria testing and treatment behaviour

    DEFF Research Database (Denmark)

    Hansen, Kristian Schultz; Lesner, Tine Hjernø; Østerdal, Lars Peter

    2016-01-01

    , ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced...... to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. RESULTS: Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs......BACKGROUND: Malaria continues to be a serious public health problem particularly in Africa. Many people infected with malaria do not access effective treatment due to high price. At the same time many individuals receiving malaria drugs do not suffer from malaria because of the common practice...

  16. Microbial profiles at baseline and not the use of antibiotics determine the clinical outcome of the treatment of chronic periodontitis

    OpenAIRE

    Bizzarro, S.; Laine, M.L.; Buijs, M.J.; Brandt, B. W.; Crielaard, W; Loos, B.G.; Zaura, E.

    2016-01-01

    Antibiotics are often used in the treatment of chronic periodontitis, which is a major cause of tooth loss. However, evidence in favour of a microbial indication for the prescription of antibiotics is lacking, which may increase the risk of the possible indiscriminate use of antibiotics, and consequent, microbial resistance. Here, using an open-ended technique, we report the changes in the subgingival microbiome up to one year post-treatment of patients treated with basic periodontal therapy ...

  17. Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Christensen, Anton Wulf; Tarp, Simon; Furst, Daniel E;

    2015-01-01

    )) for rheumatoid arthritis (RA). METHODS: We conducted a meta-epidemiological study of all trials evaluating a targeted therapy approved by regulatory authorities for treating RA. The database search was completed on December 11th 2013. Eligible trials reported ACR20 data at months 3-6 and used an add-on design......OBJECTIVE: To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs...

  18. Relationship between frequency, length, and treatment outcome of exacerbations to baseline lung function and lung density in alpha-1 antitrypsin-deficient COPD

    Directory of Open Access Journals (Sweden)

    Vijayasaratha K

    2012-11-01

    Full Text Available Kesavaperumal Vijayasaratha,1 Robert A Stockley21Lung Investigation Unit, 2Research and Development, University Hospital Birmingham NHS Trust, Birmingham, UKBackground: Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease (COPD, although factors influencing the length and frequency of each episode are poorly understood. This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin (AAT deficiency (PiZ phenotype and COPD.Methods: Daily diary cards were collected over 2 years. Patients had emphysema visualized and quantified by computed tomography scan, and had at least one documented exacerbation in the previous year.Results: The patients (n = 23 had a mean age of 52.5 years, forced expiratory volume in one second (FEV1 of 1.2 L (38.4% predicted, corrected gas transfer (KCO of 0.90 mmol/min/kPa/L (59.7% predicted, and 15th percentile lung density of 44.55 g/L. Two hundred and sixty-three exacerbations (164 treated were identified. The frequency of treated exacerbations correlated negatively with KCO% predicted (r = −0.432; P = 0.022. Exacerbation length (determined for 17 of the patients for whom diary card data through the episode were available correlated negatively with baseline 15th percentile lung density (r = −0.361; P = 0.003, and increased the longer treatment was delayed (r = 0.503; P < 0.001. Treatment delay was shorter with higher day 1 symptom score, lower baseline FEV1, FEV1/forced vital capacity, and lower 15th percentile lung density (r = −0.368, 0.272, 0.461, and 0.786; P = 0.004, 0.036, <0.001, and <0.001, respectively. Time to resolution of exacerbation after treatment initiation was not affected by treatment delay, but correlated negatively with KCO% predicted (r = −0.647; P = 0.007.Conclusion: In alpha-1 antitrypsin deficiency, the frequency and length of resolution of exacerbation were related to baseline gas transfer. Treatment

  19. Baseline depression levels do not affect efficacy of cognitive-behavioral self-help treatment for insomnia

    NARCIS (Netherlands)

    Lancee, J.; van den Bout, J.; van Straten, A.; Spoormaker, V.I.

    2013-01-01

    Background: Cognitive-behavioral therapy can effectively treat insomnia (CBT-I). Randomized controlled trials have shown efficacy of self-help CBT-I, but unclear is whether excluding depressive patients boosted treatment effects. Method: We administered unsupported self-help CBT-I to insomnia patien

  20. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure : rationale, design, and baseline characteristics of BIOSTAT-CHF

    NARCIS (Netherlands)

    Voors, Adriaan A.; Anker, Stefan D.; Cleland, John G.; Dickstein, Kenneth; Filippatos, Gerasimos; van der Harst, Pim; Hillege, Hans L.; Lang, Chim C.; ter Maaten, Jozine M.; Ng, Leong; Ponikowski, Piotr; Samani, Nilesh J.; van Veldhuisen, Dirk J.; Zannad, Faiz; Zwinderman, Aeilko H.; Metra, Marco

    2016-01-01

    AimsDespite major improvements in pharmacological and device treatments, heart failure remains a syndrome with high morbidity and mortality, poor quality of life, and high health-care costs. Given the extensive heterogeneity among patients with heart failure, substantial differences in the response

  1. Microbial profiles at baseline and not the use of antibiotics determine the clinical outcome of the treatment of chronic periodontitis

    NARCIS (Netherlands)

    Bizzarro, S.; Laine, M.L.; Buijs, M.J.; Brandt, B.W.; Crielaard, W.; Loos, B.G.; Zaura, E.

    2016-01-01

    Antibiotics are often used in the treatment of chronic periodontitis, which is a major cause of tooth loss. However, evidence in favour of a microbial indication for the prescription of antibiotics is lacking, which may increase the risk of the possible indiscriminate use of antibiotics, and consequ

  2. Baseline proteinuria, urinary osmotic pressure, and renal function as positive predictors of corticosteroids plus cyclophosphamide treatment efficacy in IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    Fang Jing; Li Wenge; Li Duo; Tan Zhao

    2014-01-01

    Background Very limited data are available on factors predictive of corticosteroids plus cyclophosphamide treatment efficacy on IgA nephropathy (IgAN).The aim of the study was to research the clinical factors predictive of treatment efficacy in IgAN.Methods One hundred and fifty-nine patients with IgAN (proteinuria ≥2 g/d and estimated glomerular filtration rate 30-89 ml·min-1·1.73 m-2) were treated with corticosteroids/cyclophosphamide followed by a 12-month follow-up.According to their response,these patients were divided into remission group (proteinuria <0.5 g/d) and non-remission group (proteinuria ≥0.5 g/d),and their clinical data collected.Results In the present study,72.96% of the individuals underwent a complete remission,and their response was related to baseline proteinuria,urinary osmotic pressure,and renal function (P <0.05).Patients with baseline proteinuria more than 3 g/d,urinary osmotic pressure greater than 600 mOsm/L,and eGFR 60-89 ml·min-1·1.73 m-2 responded well to the combination of corticosteroids and cyclophosphamide (86.90% vs.57.33%,P=0.000; 81.48% vs.64.10%,P=0.014; 83.17% vs.55.17%,P=0.000).Conclusion The response to the combination of corticosteroids and cyclophosphamide might be well associated with baseline proteinuria,urinary osmotic pressure,and renal function in patients with IgAN.

  3. Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis: A Meta-Epidemiological Study.

    Directory of Open Access Journals (Sweden)

    Anton Wulf Christensen

    Full Text Available To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs for rheumatoid arthritis (RA.We conducted a meta-epidemiological study of all trials evaluating a targeted therapy approved by regulatory authorities for treating RA. The database search was completed on December 11th 2013. Eligible trials reported ACR20 data at months 3-6 and used an add-on design. Odds ratios (ORs were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR.Sixty-two trials (19,923 RA patients were included in the primary analyses using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI 3.41 to 4.60. The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower in trials including "DMARD-naïve" patients compared with trials including "DMARD inadequate responders" (ROR = 0.45, 95%CI 0.31 to 0.66 and trials including "targeted therapy inadequate responders" (0.50, 95%CI 0.29 to 0.87, test for interaction: p = 0.0002. Longer mean disease duration was associated with a higher likelihood of responding to treatment (β = 1.05, 95%CI 1.00 to 1.11 OR's per year; p = 0.03. Analyses conducted using DAS28-remission as the outcome supported the above-mentioned findings.Our results suggest that a highly selective inclusion is not associated with greater treatment effect, as might otherwise be expected. The added benefit of a targeted therapy was lower in trials including patients who were DMARD-naïve and trials including patients with shorter disease durations.

  4. First-line antihypertensive treatment in patients with pre-diabetes: Rationale, design and baseline results of the ADaPT investigation

    Directory of Open Access Journals (Sweden)

    Bramlage Peter

    2008-07-01

    Full Text Available Abstract Background Recent clinical trials reported conflicting results on the reduction of new-onset diabetes using RAS blocking agents. Therefore the role of these agents in preventing diabetes is still not well defined. Ramipril is an ACE inhibitor (ACEi, that has been shown to reduce cardiovascular events in high risk patients and post-hoc analyses of the HOPE trial have provided evidence for its beneficial action in the prevention of diabetes. Methods The ADaPT investigation ("ACE inhibitor-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes" is a 4-year open, prospective, parallel group phase IV study. It compares an antihypertensive treatment regimen based on ramipril versus a treatment based on diuretics or betablockers. The primary evaluation criterion is the first manifestation of type 2 diabetes. The study is conducted in primary care to allow the broadest possible application of its results. The present article provides an outline of the rationale, the design and baseline characteristics of AdaPT and compares these to previous studies including ASCOT-BLPA, VALUE and DREAM. Results Until March 2006 a total of 2,015 patients in 150 general practices (general physicians and internists throughout Germany were enrolled. The average age of patients enrolled was 67.1 ± 10.3 years, with 47% being male and a BMI of 29.9 ± 5.0 kg/m2. Dyslipidemia was present in 56.5%. 37.8% reported a family history of diabetes, 57.8% were previously diagnosed with hypertension (usually long standing. The HbA1c value at baseline was 5.6 %. Compared to the DREAM study patients were older, had more frequently hypertension and patients with cardiovascular disease were not excluded. Conclusion Comparing the ADaPT design and baseline data to previous randomized controlled trial it can be acknowledged that AdaPT included patients with a high risk for diabetes development. Results are expected to be available in 2010. Data

  5. Effects of chronic treatment with the eNOS stimulator Impaza on penis length and sexual behaviors in rats with a high baseline of sexual activity.

    Science.gov (United States)

    Chu, X; Zhavbert, E S; Dugina, J L; Kheyfets, I A; Sergeeva, S A; Epstein, O I; Agmo, A

    2014-01-01

    Endothelial nitric oxide synthase (eNOS) has an important role in erection, and it also affects aspects of sexual behavior. In this experiment, we determined whether a compound enhancing the activity of eNOS, Impaza, could stimulate any aspect of sexual behavior and increase penis length in rats with a high baseline of sexual activity. For comparison, the PDE5 inhibitor sildenafil was included. Male rats were orally treated with Impaza or sildenafil for 28 days. Impaza (3 ml kg(-1)) was given daily while sildenafil (3 mg kg(-1)) was given twice weekly. Tests for sexual incentive motivation and copulatory behavior were performed just before drug treatment and at days 7, 14 and 28 of treatment. In addition, the length of the protruding penis at mount, intromission and ejaculation was measured. Impaza but not sildenafil increased penis length at mount after 14 and 28 days of treatment. The compounds failed to modify sexual incentive motivation or copulatory behavior. It is suggested that Impaza enhanced intracavernous pressure, as such a pressure increase is the most likely explanation for enhanced penis length at mount. This effect, together with an absence of motivational actions, suggests that Impaza may be the most valuable treatment for erectile dysfunction.

  6. Baseline HCV Antibody Prevalence and Risk Factors among Drug Users in China’s National Methadone Maintenance Treatment Program

    Science.gov (United States)

    Rou, Keming; Zhao, Yan; Cao, Xiaobin; Luo, Wei; Liu, Enwu; Wu, Zunyou

    2016-01-01

    Background Hepatitis C virus (HCV) is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT) program. Methods Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution. Results Anti-HCV screening was positive for 54.6% of clients upon MMT entry between 2004 and 2012. HCV antibody prevalence at entry declined from 66.8% in 2005 to 45.9% in 2012. The most significant predictors of HCV seropositivity were injecting drug use (adjusted odds ratio [AOR]: 8.34, 95% confidence interval [CI]: 8.17–8.52, p<0.0001) and a history of drug use ≥9 years (AOR: 2.01, 95% CI: 1.96–2.06, p<0.0001). Being female, of Uyghur or Zhuang ethnicity, and unmarried were identified as demographic risk factors (all p-values<0.0001). Of the 28 provincial-level divisions included in the study, we found that 5 divisions had HCV antibody prevalence above 70% and 20 divisions above 50%. The HCV screening rate within 6 months after MMT entry greatly increased from 30.4% in 2004 to 93.1% in 2012. Conclusions The current HCV antibody prevalence remains alarmingly high among MMT clients throughout most provincial-level divisions in China, particularly among injecting drug users and females. A comprehensive prevention strategy is needed to control the HCV epidemic among MMT clients in China. PMID:26906025

  7. Baseline HCV Antibody Prevalence and Risk Factors among Drug Users in China's National Methadone Maintenance Treatment Program.

    Directory of Open Access Journals (Sweden)

    Changhe Wang

    Full Text Available Hepatitis C virus (HCV is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT program.Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution.Anti-HCV screening was positive for 54.6% of clients upon MMT entry between 2004 and 2012. HCV antibody prevalence at entry declined from 66.8% in 2005 to 45.9% in 2012. The most significant predictors of HCV seropositivity were injecting drug use (adjusted odds ratio [AOR]: 8.34, 95% confidence interval [CI]: 8.17-8.52, p<0.0001 and a history of drug use ≥9 years (AOR: 2.01, 95% CI: 1.96-2.06, p<0.0001. Being female, of Uyghur or Zhuang ethnicity, and unmarried were identified as demographic risk factors (all p-values<0.0001. Of the 28 provincial-level divisions included in the study, we found that 5 divisions had HCV antibody prevalence above 70% and 20 divisions above 50%. The HCV screening rate within 6 months after MMT entry greatly increased from 30.4% in 2004 to 93.1% in 2012.The current HCV antibody prevalence remains alarmingly high among MMT clients throughout most provincial-level divisions in China, particularly among injecting drug users and females. A comprehensive prevention strategy is needed to control the HCV epidemic among MMT clients in China.

  8. Pain Treatments for Nursing Home Residents with Advanced Dementia and Substantial Impaired Communication: A Cross-Sectional Analysis at Baseline of a Cluster Randomized Controlled Trial.

    Science.gov (United States)

    Liu, Justina Yat Wa; Leung, Doris Y P

    2016-09-28

    OBJECTIVES : This is a cross-sectional analysis at baseline of a cluster randomized controlled trial to identify factors associated with the use of pharmacological and nonpharmacological pain treatments by nursing home residents with dementia and impaired communication. METHODS : One hundred thirty-four residents with dementia and impaired communication were recruited. Nine of them were excluded because data on their pain treatments were missing, resulting in 125 for analysis. Hierarchical generalized estimating equations analyses controlling for the clustering effect of nursing homes were used to identify factors associated with the use of pharmacological and nonpharmacological pain treatments. RESULTS : Although all participants had a confirmed pain condition, only 23 (18.4%) and 45 (36%) had received pharmacological or nonpharmacological pain treatments, respectively. Participants with a higher ability to communicate (P = 0.031) and fewer pain locations were found to be more likely to receive pain medications, with the impact of communication ability being greater among participants with better cognitive status than among those with poor cognitive status. Participants who had been living in the home longer and who were more dependent were less likely to receive nonpharmacological treatments. CONCLUSION : Suboptimal pain management was common among this population. Severe impairment in the ability to communicate is a major reason for the underuse of pain medications. Staff may become desensitized and fail to perceive subtle changes in the residents' behavior as indicative of pain, leading to the underadministering of nonpharmacological treatments. To improve this situation, it is suggested that observational pain assessments be systematically carried out in nursing homes.

  9. Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.

    Science.gov (United States)

    Tyndale, Rachel F; Zhu, Andy Z X; George, Tony P; Cinciripini, Paul; Hawk, Larry W; Schnoll, Robert A; Swan, Gary E; Benowitz, Neal L; Heitjan, Daniel F; Lerman, Caryn

    2015-01-01

    CHRNA5-A3-B4 variants, rs16969968, rs588765 and rs578776, are consistently associated with tobacco consumption among smokers, but the association with smoking cessation is less consistent. Among the studies that reported significant associations with cessation, the effects were observed in smokers treated with placebo treatment in some studies and conversely in those receiving active pharmacological therapy (bupropion and nicotine replacement therapies) in others. Thus, it remains unclear whether CHRNA5-A3-B4 is a useful marker for optimizing smoking cessation. Using data from 654 Caucasian smokers treated with placebo, nicotine patch or varenicline, we investigated whether CHRNA5-A3-B4 variants were associated with smoking cessation outcomes, and whether there were significant genotype-by-treatment or haplotype-by-treatment interactions. We observed no significant associations between CHRNA5-A3-B4 variants and smoking cessation, despite replicating previous associations with baseline tobacco consumption. At end of treatment the effect size on smoking cessation in the placebo, patch and varenicline groups for rs16969968 [GG vs. GA+AA] was OR = 0.66 (P = 0.23), OR = 1.01 (P = 0.99), and OR = 1.30 (P = 0.36) respectively, of rs588765 [CC vs. CT+TT] was OR = 0.96 (P = 0.90), OR = 0.84 (P = 0.58), and OR = 0.74 (P = 0.29) respectively, and for rs578776 [GG vs. GA+AA] on smoking cessation was OR = 1.02 (P = 0.95), OR = 0.75 (P = 0.35), and OR = 1.20 (P = 0.51) respectively. Furthermore, we observed no associations with cessation using the CHRNA5-A3-B4 haplotype (constructed using rs16969968 and rs588765), nor did we observe any significant genotype-by-treatment interactions, with or without adjusting for the rate of nicotine metabolism (all P>0.05). We also observed no significant genetic associations with 6 month or 12 month smoking abstinence. In conclusion, we found no association between CHRNA5-A3-B4 variants and smoking cessation rates in this clinical trial

  10. Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.

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    Rachel F Tyndale

    Full Text Available CHRNA5-A3-B4 variants, rs16969968, rs588765 and rs578776, are consistently associated with tobacco consumption among smokers, but the association with smoking cessation is less consistent. Among the studies that reported significant associations with cessation, the effects were observed in smokers treated with placebo treatment in some studies and conversely in those receiving active pharmacological therapy (bupropion and nicotine replacement therapies in others. Thus, it remains unclear whether CHRNA5-A3-B4 is a useful marker for optimizing smoking cessation. Using data from 654 Caucasian smokers treated with placebo, nicotine patch or varenicline, we investigated whether CHRNA5-A3-B4 variants were associated with smoking cessation outcomes, and whether there were significant genotype-by-treatment or haplotype-by-treatment interactions. We observed no significant associations between CHRNA5-A3-B4 variants and smoking cessation, despite replicating previous associations with baseline tobacco consumption. At end of treatment the effect size on smoking cessation in the placebo, patch and varenicline groups for rs16969968 [GG vs. GA+AA] was OR = 0.66 (P = 0.23, OR = 1.01 (P = 0.99, and OR = 1.30 (P = 0.36 respectively, of rs588765 [CC vs. CT+TT] was OR = 0.96 (P = 0.90, OR = 0.84 (P = 0.58, and OR = 0.74 (P = 0.29 respectively, and for rs578776 [GG vs. GA+AA] on smoking cessation was OR = 1.02 (P = 0.95, OR = 0.75 (P = 0.35, and OR = 1.20 (P = 0.51 respectively. Furthermore, we observed no associations with cessation using the CHRNA5-A3-B4 haplotype (constructed using rs16969968 and rs588765, nor did we observe any significant genotype-by-treatment interactions, with or without adjusting for the rate of nicotine metabolism (all P>0.05. We also observed no significant genetic associations with 6 month or 12 month smoking abstinence. In conclusion, we found no association between CHRNA5-A3-B4 variants and smoking cessation rates in this clinical

  11. The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901

    Science.gov (United States)

    Dvorak, Christopher C.; Cowan, Morton J.; Logan, Brent R.; Notarangelo, Luigi D.; Griffith, Linda M.; Puck, Jennifer M.; Kohn, Donald B.; Shearer, William T.; O'Reilly, Richard J.; Fleisher, Thomas A.; Pai, Sung-Yun; Hanson, I. Celine; Pulsipher, Michael A.; Fuleihan, Ramsay; Filipovich, Alexandra; Goldman, Frederick; Kapoor, Neena; Small, Trudy; Smith, Angela; Chan, Ka-Wah; Cuvelier, Geoff; Heimall, Jennifer; Knutsen, Alan; Loechelt, Brett; Moore, Theodore; Buckley, Rebecca H.

    2013-01-01

    The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92%) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92%) were treated with HCT within 1–2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes. PMID:23818196

  12. Treatment guided by rapid diagnostic tests for malaria in Tanzanian children: safety and alternative bacterial diagnoses

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    Sykes Alma

    2011-10-01

    Full Text Available Abstract Background WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT. However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa. Methods Children 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days. Results Over the course of one year, 965 children were enrolled; 158 (16.4% were RDT-positive and treated with artemether-lumefantrine and 807 (83.4% were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6% children became RDT-positive after enrolment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrolment. In addition, 12 (1.2% children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9% children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95%CI 96.9-98.7 and specificity of 96.3% (95%CI 96.3-98.4. Conclusions Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive

  13. Malaria Treatment Policy Change and Implementation: The Case of Uganda

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    Miriam Nanyunja

    2011-01-01

    Full Text Available Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.

  14. Malaria treatment policy change and implementation: the case of Uganda.

    Science.gov (United States)

    Nanyunja, Miriam; Nabyonga Orem, Juliet; Kato, Frederick; Kaggwa, Mugagga; Katureebe, Charles; Saweka, Joaquim

    2011-01-01

    Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ) was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.

  15. Utility of baseline, interim and end-of-treatment 18F-FDG PET/CT in extranodal natural killer/T-cell lymphoma patients treated with L-asparaginase/pegaspargase

    Science.gov (United States)

    Chang, Yu; Fu, Xiaorui; Sun, Zhenchang; Xie, Xinli; Wang, Ruihua; Li, Zhaoming; Zhang, Xudong; Sheng, Guangyao; Zhang, Mingzhi

    2017-01-01

    Positron emission tomography-computed tomography (PET/CT) is widely used for initial staging and monitoring treatment responses in Hodgkin and diffuse large B-cell lymphoma. However, its prognostic value in extranodal natural killer (NK)/T-cell lymphoma (ENKL) remains unclear. Here, we conducted a retrospective study to determine the impact of PET/CT in ENKL. Fifty-two patients newly diagnosed with ENKL were enrolled. Baseline maximum standardized uptake values (SUVmax), whole-body metabolic tumor volume (WBMTV) and whole-body total lesion glycolysis (WBTLG) were recorded. Additionally, interim PET/CT (I-PET) and end-of-treatment PET/CT (E-PET) results were scored using a 5-point scale. Patients were divided into groups using baseline parameter cut-off values; significant differences were found in overall survival (OS) and progression-free survival (PFS) between the high and low WBMTV and WBTLG groups and in OS between the two SUVmax groups. Positive I-PET and E-PET results predicted inferior PFS and OS. A multivariate analysis showed that baseline WBTLG, I-PET and E-PET results were associated with PFS and OS, and baseline SUVmax was an independent predictor of OS. Thus, baseline WBTLG, I-PET and E-PET results are good predictors of PFS and OS in ENKL patients who received L-asparaginase/pegaspargase in their first-line treatment, and baseline SUVmax is a valuable tool for assessing OS. PMID:28117395

  16. Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya

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    Watsierah Carren A

    2012-12-01

    Full Text Available Abstract Background Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers’ knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers’ knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. Methods A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription, was collected. Results Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100% in public and majority (98.4% in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039 and severe malaria (P P = 0.002 in children and adults

  17. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901.

    Science.gov (United States)

    Dvorak, Christopher C; Cowan, Morton J; Logan, Brent R; Notarangelo, Luigi D; Griffith, Linda M; Puck, Jennifer M; Kohn, Donald B; Shearer, William T; O'Reilly, Richard J; Fleisher, Thomas A; Pai, Sung-Yun; Hanson, I Celine; Pulsipher, Michael A; Fuleihan, Ramsay; Filipovich, Alexandra; Goldman, Frederick; Kapoor, Neena; Small, Trudy; Smith, Angela; Chan, Ka-Wah; Cuvelier, Geoff; Heimall, Jennifer; Knutsen, Alan; Loechelt, Brett; Moore, Theodore; Buckley, Rebecca H

    2013-10-01

    The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.

  18. Abriendo Puertas: baseline findings from an integrated intervention to promote prevention, treatment and care among FSW living with HIV in the Dominican Republic.

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    Yeycy Donastorg

    Full Text Available Female sex workers (FSW are often the focus of primary HIV prevention efforts. However, little attention has been paid to the prevention, treatment, and care needs of FSW living with HIV. Based on formative research, we developed an integrated model to promote prevention and care for FSW living with HIV in Santo Domingo, Dominican Republic, including (1 individual counseling and education; (2 peer navigation; (3 clinical provider training; and (4 community mobilization. We enrolled 268 FSW living with HIV into the intervention and conducted socio-behavioral surveys, sexually transmitted infection (STI testing, and viral load (VL assessments. We used multivariate logistic regression to identify behavioral and socio-demographic factors associated with detectable VL (>50 copies/mL and STI prevalence. Over half of all participants (51.9% had a detectable VL, even though most received HIV-related care in the last 6 months (85.1% and were currently on anti-retroviral treatment (ART (72.4%. Factors positively associated with a detectable VL included being 18-35 years of age (Adjusted Odds Ratio [AOR] 2.46, 95% CI 1.31-4.60, having ever used drugs (AOR 2.34, 95% CI 1.14-4.79, and having ever interrupted ART (AOR 3.09, 95% CI 1.44-6.59. Factors protective against having a detectable VL included being single (AOR 0.45, 95% 0.20-0.98 and being currently on ART (AOR 0.17, 95% CI 0.07-0.41. Nearly one-quarter (23.1% had an STI, which was associated with being single (AOR 3.21, 95% CI 1.27-8.11 and using drugs in the last 6 months (AOR 3.54, 95% CI 1.32-9.45. Being on ART was protective against STI (AOR 0.51, 95% CI 0.26-1.00. Baseline findings indicate significant barriers to VL suppression and STI prevention among FSW living with HIV and highlight gaps in the continuum of HIV care and treatment. These findings have important implications for both the individual health of FSW and population-level HIV transmission dynamics.

  19. Combined treatment with formoterol and tiotropium is more efficacious than treatment with tiotropium alone in patients with chronic obstructive pulmonary disease, regardless of smoking status, inhaled corticosteroid use, baseline severity, or gender.

    Science.gov (United States)

    Tashkin, Donald P; Varghese, Santosh T

    2011-02-01

    A recent randomized, double-blind, parallel-group, active-controlled, multicenter study of 255 patients ≥ 40 years of age with chronic obstructive pulmonary disease (COPD) showed that combined formoterol (FOR) and tiotropium (TIO) treatment in patients with COPD significantly improved lung function as well as symptoms and other patient-reported outcomes compared with TIO alone. FOR and TIO are long-acting bronchodilators that represent the β₂-adrenergic agonist and anticholinergic classes, respectively. However, the possible influence of smoking status, inhaled corticosteroid (ICS) use, baseline disease severity, and gender differences on bronchodilator efficacy requires further investigation. Using data from the previously published study mentioned above, a post hoc analysis was performed to examine the efficacy of combined FOR + TIO treatment compared with TIO monotherapy in subgroup analyses of men and women, current and ex-smokers, ICS users and non-ICS users, and patients with moderate and severe/very severe COPD. Efficacy comparisons were based on the changes in forced expiratory volume in 1 s measured 0-4 h after the morning dose (FEV₁ AUC₀₋₄h). After a run-in period, patients were treated for 12 weeks with either FOR 12 μg twice daily (BID) plus TIO 18 μg once daily (QD) in the morning (AM, n = 124) or with FOR placebo BID plus TIO 18 μg QD AM (n = 131). The least squares mean change from baseline in the normalized FEV₁ AUC₀₋₄h was assessed using analysis of covariance. With the exception of treatment differences at week 4 in smokers and subjects with "very severe" COPD, and at weeks 4, 8, and 12 for ICS users and non-ICS users (p values not determined), FOR + TIO was significantly superior (P ICS use, or COPD severity. We conclude that coadministered FOR + TIO significantly improves lung function compared with TIO treatment alone in COPD patients regardless of differences in patient subgroups.

  20. Improving childhood malaria treatment and referral practices by training patent medicine vendors in rural south-east Nigeria

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    Uzochukwu Benjamin SC

    2009-11-01

    Full Text Available Abstract Background Malaria remains a major cause of morbidity and mortality among children under five years of age in Nigeria. Most of the early treatments for fever and malaria occur through self-medication with anti-malarials bought over-the-counter (OTC from untrained drug vendors. Self-medication through drug vendors can be ineffective, with increased risks of drug toxicity and development of drug resistance. Global malaria control initiatives highlights the potential role of drug vendors to improve access to early effective malaria treatment, which underscores the need for interventions to improve treatment obtained from these outlets. This study aimed to determine the feasibility and impact of training rural drug vendors on community-based malaria treatment and advice with referral of severe cases to a health facility. Methods A drug vendor-training programme was carried out between 2003 and 2005 in Ugwuogo-Nike, a rural community in south-east Nigeria. A total of 16 drug vendors were trained and monitored for eight months. The programme was evaluated to measure changes in drug vendor practice and knowledge using exit interviews. In addition, home visits were conducted to measure compliance with referral. Results The intervention achieved major improvements in drug selling and referral practices and knowledge. Exit interviews confirmed significant increases in appropriate anti-malarial drug dispensing, correct history questions asked and advice given. Improvements in malaria knowledge was established and 80% compliance with referred cases was observed during the study period, Conclusion The remarkable change in knowledge and practices observed indicates that training of drug vendors, as a means of communication in the community, is feasible and strongly supports their inclusion in control strategies aimed at improving prompt effective treatment of malaria with referral of severe cases.

  1. Clinical tolerability of artesunate-amodiaquine versus comparator treatments for uncomplicated falciparum malaria: an individual-patient analysis of eight randomized controlled trials in sub-Saharan Africa

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    Zwang Julien

    2012-08-01

    Full Text Available Abstract Background The widespread use of artesunate-amodiaquine (ASAQ for treating uncomplicated malaria makes it important to gather and analyse information on its tolerability. Methods An individual-patient tolerability analysis was conducted using data from eight randomized controlled clinical trials conducted at 17 sites in nine sub-Saharan countries comparing ASAQ to other anti-malarial treatments. All patients who received at least one dose of the study drug were included in the analysis. Differences in adverse event (AE and treatment emergent adverse event (TEAE were analysed by Day 28. Results Of the 6,179 patients enrolled (74% Conclusion ASAQ was comparatively well-tolerated. Safety information is important, and must be collected and analysed in a standardized way. TEAEs are a more objective measure of treatment-induced toxicity.

  2. The relationship between baseline Organizational Readiness to Change Assessment subscale scores and implementation of hepatitis prevention services in substance use disorders treatment clinics: a case study

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    Hagedorn Hildi J

    2010-06-01

    Full Text Available Abstract Background The Organizational Readiness to Change Assessment (ORCA is a measure of organizational readiness for implementing practice change in healthcare settings that is organized based on the core elements and sub-elements of the Promoting Action on Research Implementation in Health Services (PARIHS framework. General support for the reliability and factor structure of the ORCA has been reported. However, no published study has examined the utility of the ORCA in a clinical setting. The purpose of the current study was to examine the relationship between baseline ORCA scores and implementation of hepatitis prevention services in substance use disorders (SUD clinics. Methods Nine clinic teams from Veterans Health Administration SUD clinics across the United States participated in a six-month training program to promote evidence-based practices for hepatitis prevention. A representative from each team completed the ORCA evidence and context subscales at baseline. Results Eight of nine clinics reported implementation of at least one new hepatitis prevention practice after completing the six-month training program. Clinic teams were categorized by level of implementation-high (n = 4 versus low (n = 5-based on how many hepatitis prevention practices were integrated into their clinics after completing the training program. High implementation teams had significantly higher scores on the patient experience and leadership culture subscales of the ORCA compared to low implementation teams. While not reaching significance in this small sample, high implementation clinics also had higher scores on the research, clinical experience, staff culture, leadership behavior, and measurement subscales as compared to low implementation clinics. Conclusions The results of this study suggest that the ORCA was able to measure differences in organizational factors at baseline between clinics that reported high and low implementation of practice

  3. TWRS privatization process technical baseline

    Energy Technology Data Exchange (ETDEWEB)

    Orme, R.M.

    1996-09-13

    The U.S. Department of Energy (DOE) is planning a two-phased program for the remediation of Hanford tank waste. Phase 1 is a pilot program to demonstrate the procurement of treatment services. The volume of waste treated during the Phase 1 is a small percentage of the tank waste. During Phase 2, DOE intends to procure treatment services for the balance of the waste. The TWRS Privatization Process Technical Baseline (PPTB) provides a summary level flowsheet/mass balance of tank waste treatment operations which is consistent with the tank inventory information, waste feed staging studies, and privatization guidelines currently available. The PPTB will be revised periodically as privatized processing concepts are crystallized.

  4. A Randomised, Double-Blind, Placebo-Controlled Trial with Vitamin D3 in MS: Subgroup Analysis of Patients with Baseline Disease Activity Despite Interferon Treatment

    Directory of Open Access Journals (Sweden)

    J. Åivo

    2012-01-01

    Full Text Available We present a subgroup analysis of the first double-blind, placebo-controlled, randomised trial with vitamin D3 in MS. In the overall study population, there were 34 patients in the vitamin D arm and 32 patients in the placebo arm. All the patients were using interferon-β-1b (IFNB therapy. The subgroup consisted of 15 patients in the vitamin D arm and 15 patients in the placebo arm, who had either at least one relapse during the year preceding the study or enhancing T1 lesions at the baseline MRI scan. We measured the total number of MRI T1 enhancing lesions, the number of new/enlarging T2 lesions and T2 lesion volume (BOD (mm3, EDSS (Expanded Disability Status Scale, annual relapse Rate (ARR, timed 25-foot walk (T25FW, and timed 10-foot tandem walk (TT10W at baseline and at 12 months in the vitamin D-treated and in the placebo-treated patients. There was a statistically significant reduction in the number of T1 enhancing lesions, a smaller T2 lesion volume growth and less new/enlarging T2 brain MRI lesions in the vitamin D3-treated than in the placebo-treated subgroup patients. The MRI results were slightly more pronounced in the subgroup than in the overall study population.

  5. Magic Baseline Beta Beam

    CERN Document Server

    Agarwalla, Sanjib Kumar; Raychaudhuri, Amitava

    2007-01-01

    We study the physics reach of an experiment where neutrinos produced in a beta-beam facility at CERN are observed in a large magnetized iron calorimeter (ICAL) at the India-based Neutrino Observatory (INO). The CERN-INO distance is close to the so-called "magic" baseline which helps evade some of the parameter degeneracies and allows for a better measurement of the neutrino mass hierarchy and $\\theta_{13}$.

  6. The TDAQ Baseline Architecture

    CERN Multimedia

    Wickens, F J

    The Trigger-DAQ community is currently busy preparing material for the DAQ, HLT and DCS TDR. Over the last few weeks a very important step has been a series of meetings to complete agreement on the baseline architecture. An overview of the architecture indicating some of the main parameters is shown in figure 1. As reported at the ATLAS Plenary during the February ATLAS week, the main area where the baseline had not yet been agreed was around the Read-Out System (ROS) and details in the DataFlow. The agreed architecture has: Read-Out Links (ROLs) from the RODs using S-Link; Read-Out Buffers (ROB) sited near the RODs, mounted in a chassis - today assumed to be a PC, using PCI bus at least for configuration, control and monitoring. The baseline assumes data aggregation, in the ROB and/or at the output (which could either be over a bus or in the network). Optimization of the data aggregation will be made in the coming months, but the current model has each ROB card receiving input from 4 ROLs, and 3 such c...

  7. Patients with ≥ 20 × 10(9)/l platelets at baseline may have a prompt response to romiplostim during the early phase of treatment: an italian single-institution experience.

    Science.gov (United States)

    Baldini, Simone; Rigacci, Luigi; Carrai, Valentina; Alterini, Renato; Fjerza, Rajmonda; Bosi, Alberto

    2012-01-01

    Patients with chronic immune thrombocytopenia treated with romiplostim may benefit from a higher starting dose when a rapid increase in count is needed, but it could be avoided in those with a prompt response to the standard dosage. We hypothesized that a platelet count ≥ 20 × 10(9)/l at baseline could distinguish subjects with such response from those with a delayed one during the early phase of treatment. Our work is a retrospective and single-institution analysis comparing the median platelet count, the median weekly dosage of romiplostim and the median number of weekly platelet counts < 50 × 10(9)/l between patients with a baseline ≥ 20 × 10(9)/l platelets (n=10, 2 splenectomized) and those with a lower one (n=8, 3 splenectomized) during the first month of treatment with romiplostim. The results show a higher median platelet count (79,5 vs 40,5 × 10(9)/l, p=0,002) and a lower median dose of romiplostim (1 vs 2 mcg/kg/week, p=0,01) in subjects with a baseline ≥ 20 × 10(9)/l platelets, who also had a trend of less weekly counts < 50 × 10(9)/l platelets (1 vs 2, p=0,054). These data suggest that patients with ≥ 20 × 10(9)/l platelets at baseline may achieve a prompt response with the standard dose of romiplostim, but further and larger data are needed in order to assess whether it can be considered in clinical practice.

  8. Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events.

    Science.gov (United States)

    Bray, Paul F; Larson, Joseph C; Lacroix, Andrea Z; Manson, Joann; Limacher, Marian C; Rossouw, Jacques E; Lasser, Norman L; Lawson, William E; Stefanick, Marcia L; Langer, Robert D; Margolis, Karen L

    2008-06-01

    Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio > or =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio disease with CEE with or without MPA irrespective of hs-CRP.

  9. PfHRP2 and PfLDH antigen detection for monitoring the efficacy of artemisinin-based combination therapy (ACT in the treatment of uncomplicated falciparum malaria

    Directory of Open Access Journals (Sweden)

    Deloron Philippe

    2009-09-01

    Full Text Available Abstract Background An assessment of the accuracy of two malaria rapid diagnostic tests (RDT for the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2 or Pf lactate dehydrogenase (PfLDH was undertaken in children aged between six and 59 months included in an anti-malarial efficacy study in Benin. Methods In Allada (Benin, 205 children aged 6-59 months with falciparum malaria received either artesunate-amodiaquine (ASAQ, artemether-lumefantrine (AL, or sulphadoxine-pyrimethamine (SP. Children included in the study were simultaneously followed by both RDT and high-quality microscopy for up to 42 days. Results At the time of inclusion, PfHRP2-based tests were positive in 203 children (99% and PfLDH-based tests were positive in 204 (99.5%. During follow-up, independent of the treatment received, only 17.3% (28/162 of children effectively cured were negative with the PfHRP2 RDT at day 3, with a gradual increase in specificity until day 42. The specificity of antigen detection with the PfLDH test was 87% (141/162 on day 3, and between 92% and 100% on days 7 to 42. A statistical difference was observed between the persistence of PfHRP2 and PfLDH antigenaemia during follow-up in children treated with artemisinin-based combination therapy (ACT but not with SP. Conclusion Although both RDTs are as sensitive as microscopy in detecting true malaria cases, the PfHRP2 RDT had very low specificity during follow-up until day 28. On the other hand, the PfLDH test could be used to detect failures and, therefore, to assess anti-malarial efficacy.

  10. METODO, a prospective observational study to assess the efficacy and tolerability of methadone in heroin-addicted patients undergoing a methadone maintenance treatment: preliminary results at baseline evaluation.

    Science.gov (United States)

    D'Egidio, Pietro Fausto; Bignamini, Emanuele; De Vivo, Enrico; Leonardi, Claudio; Pieri, Maria Chiara; González-Saiz, Francisco; Lucchini, Alfio

    2013-12-01

    METODO (methadone efficacy therapy optimization dosage on-going) is a prospective observational study to assess the efficacy and tolerability of methadone in 500 heroin-addicted patients taking a methadone maintenance treatment, enrolled through 2010 to 2011 in five Italian sites, observed over 2 years. The Opiate Dosage Adequacy Scale has been used for the evaluation of the "adequacy" of the methadone dosage and to stratify patients in adequate and not adequate groups. The treatment efficacy has been evaluated in correlation to the dosage adequacy during the visits. Moreover, patients have been evaluated according to the retention rate and duration of retention in treatment and a series of questionnaires.

  11. In-treatment midwall and endocardial fractional shortening predict cardiovascular outcome in hypertensive patients with preserved baseline systolic ventricular function: the Losartan Intervention For Endpoint reduction study

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Gerdts, Eva; Palmieri, Vittorio;

    2010-01-01

    Endocardial fractional shortening (EFS) and midwall shortening (MWS) are impaired in patients with left ventricular hypertrophy. However, it remains unknown whether improvement of left ventricular systolic function during treatment reduces cardiovascular morbidity and mortality in hypertensive pa...

  12. Depression CBT treatment gains among HIV-infected persons with a history of injection drug use varies as a function of baseline substance use

    OpenAIRE

    Labbe, Allison K.; O'Cleirigh, Conall M.; Stein, Michael; Safren, Steven A.

    2015-01-01

    Depression and substance use, the most common comorbidities with HIV, are both associated with poor treatment outcomes and accelerated HIV disease progression. Though previous research has demonstrated short-term and follow-up success for cognitive behavioral therapy for adherence and depression (CBT-AD) on depression outcomes among patients with HIV in care (Safren et al., 2009) and among patients with HIV in active substance abuse treatment for injection drug use (IDU) (Safren et al., 2012)...

  13. Baseline quasispecies selection and novel mutations contribute to emerging resistance-associated substitutions in hepatitis C virus after direct-acting antiviral treatment

    Science.gov (United States)

    Kai, Yugo; Hikita, Hayato; Morishita, Naoki; Murai, Kazuhiro; Nakabori, Tasuku; Iio, Sadaharu; Hagiwara, Hideki; Imai, Yasuharu; Tamura, Shinji; Tsutsui, Syusaku; Naito, Masafumi; Nishiuchi, Meiko; Kondo, Yasuteru; Kato, Takanobu; Suemizu, Hiroshi; Yamada, Ryoko; Oze, Tsugiko; Yakushijin, Takayuki; Hiramatsu, Naoki; Sakamori, Ryotaro; Tatsumi, Tomohide; Takehara, Tetsuo

    2017-01-01

    Resistance-associated substitutions (RASs) in hepatitis C virus (HCV) appear upon failure of treatment with direct-acting antivirals (DAAs). However, their origin has not been clarified in detail. Among 11 HCV genotype 1b patients who experienced virologic failure with asunaprevir (ASV)/daclatasvir (DCV), 10 had major NS5A L31M/V-Y93H variants after treatment. L31M/V-Y93H variants were detected as a minor clone before therapy in 6 patients and were the most closely related to the post-treatment variants by phylogenetic tree analysis in 4 patients. Next, to consider the involvement of a trace amount of pre-existing variants below the detection limit, we analysed human hepatocyte chimeric mice infected with DAA-naïve patient serum. L31V-Y93H variants emerged after treatment with ledipasvir (LDV)/GS-558093 (nucleotide NS5B inhibitor) and decreased under the detection limit, but these variants were dissimilar to the L31V-Y93H variants reappearing after ASV/DCV re-treatment. Finally, to develop an infection derived from a single HCV clone, we intrahepatically injected full-genome HCV RNA (engineered based on the wild-type genotype 1b sequence) into chimeric mice. A new Y93H mutation actually occurred in this model after LDV monotherapy failure. In conclusion, post-treatment RASs appear by 2 mechanisms: the selection of pre-existing substitutions among quasispecies and the generation of novel mutations during therapy. PMID:28134353

  14. The impact of cardiovascular risk, baseline LDL-cholesterol, treatment dose and adherence on cost-effectiveness of statins in newly diagnosed diabetes patients

    NARCIS (Netherlands)

    De Vries, Dianna; Hak, Eelko; Postma, Maarten J.

    2015-01-01

    Background: Statins have shown to be cost-effective in most diabetes patients. Treatment decisions in patients newly diagnosed with diabetes are primarily based on the cardiovascular risk. The effect of statins is, however, primarily based on the LDL-cholesterol reduction that is achieved, which is

  15. Simeprevir and Sofosbuvir Combination Treatment in a Patient with HCV Cirrhosis and HbS Beta 0-Thalassemia: Efficacy and Safety despite Baseline Hyperbilirubinemia.

    Science.gov (United States)

    Papadopoulos, Nikolaos; Deutsch, Melanie; Georgalas, Athanasios; Poulakidas, Helias; Karnesis, Lazaros

    2016-01-01

    Hyperbilirubinemia is an adverse reaction of simeprevir (SMV). The majority of these patients were taking concurrent ribavirin presenting elevated unconjugated hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with elevated bilirubin level have also been reported in patients with decompensated cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia and recently diagnosed compensated cirrhosis due to chronic hepatitis C infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She was considered as illegible for pegylated-interferon-free treatment with direct acting antivirals and a course with simeprevir and sofosbuvir (SOF) combination for twelve weeks was planned. Hyperbilirubinemia developed from the beginning with peak values during the 3rd month of treatment. However, no findings of liver decompensation were noticed. Hyperbilirubinemia was benign and fully reversible and our patient finally achieved sustained virological response 24 weeks after the end of treatment.

  16. Simeprevir and Sofosbuvir Combination Treatment in a Patient with HCV Cirrhosis and HbS Beta 0-Thalassemia: Efficacy and Safety despite Baseline Hyperbilirubinemia

    Science.gov (United States)

    Deutsch, Melanie; Georgalas, Athanasios; Poulakidas, Helias; Karnesis, Lazaros

    2016-01-01

    Hyperbilirubinemia is an adverse reaction of simeprevir (SMV). The majority of these patients were taking concurrent ribavirin presenting elevated unconjugated hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with elevated bilirubin level have also been reported in patients with decompensated cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia and recently diagnosed compensated cirrhosis due to chronic hepatitis C infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She was considered as illegible for pegylated-interferon-free treatment with direct acting antivirals and a course with simeprevir and sofosbuvir (SOF) combination for twelve weeks was planned. Hyperbilirubinemia developed from the beginning with peak values during the 3rd month of treatment. However, no findings of liver decompensation were noticed. Hyperbilirubinemia was benign and fully reversible and our patient finally achieved sustained virological response 24 weeks after the end of treatment. PMID:27042368

  17. Simeprevir and Sofosbuvir Combination Treatment in a Patient with HCV Cirrhosis and HbS Beta 0-Thalassemia: Efficacy and Safety despite Baseline Hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Nikolaos Papadopoulos

    2016-01-01

    Full Text Available Hyperbilirubinemia is an adverse reaction of simeprevir (SMV. The majority of these patients were taking concurrent ribavirin presenting elevated unconjugated hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with elevated bilirubin level have also been reported in patients with decompensated cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia and recently diagnosed compensated cirrhosis due to chronic hepatitis C infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She was considered as illegible for pegylated-interferon-free treatment with direct acting antivirals and a course with simeprevir and sofosbuvir (SOF combination for twelve weeks was planned. Hyperbilirubinemia developed from the beginning with peak values during the 3rd month of treatment. However, no findings of liver decompensation were noticed. Hyperbilirubinemia was benign and fully reversible and our patient finally achieved sustained virological response 24 weeks after the end of treatment.

  18. Daily baseline skin care in the prevention, treatment, and supportive care of skin toxicity in oncology patients: recommendations from a multinational expert panel.

    Science.gov (United States)

    Bensadoun, René-Jean; Humbert, Phillipe; Krutman, Jean; Luger, Thomas; Triller, Raoul; Rougier, André; Seite, Sophie; Dreno, Brigitte

    2013-01-01

    Skin reactions due to radiotherapy and chemotherapy are a significant problem for an important number of cancer patients. While effective for treating cancer, they disturb cutaneous barrier function, causing a reaction soon after initiation of treatment that impacts patient quality of life. Managing these symptoms with cosmetics and nonpharmaceutical skin care products for camouflage or personal hygiene may be important for increasing patient self-esteem. However, inappropriate product choice or use could worsen side effects. Although recommendations exist for the pharmaceutical treatment of skin reactions, there are no recommendations for the choice or use of dermatologic skin care products for oncology patients. The present guidelines were developed by a board of European experts in dermatology and oncology to provide cancer care professionals with guidance for the appropriate use of non-pharmaceutical, dermocosmetic skin care management of cutaneous toxicities associated with radiotherapy and systemic chemotherapy, including epidermal growth factor inhibitors and monoclonal antibodies. The experts hope that these recommendations will improve the management of cutaneous side effects and hence quality of life for oncology patients.

  19. Long Baseline Neutrino Experiments

    Science.gov (United States)

    Mezzetto, Mauro

    2016-05-01

    Following the discovery of neutrino oscillations by the Super-Kamiokande collaboration, recently awarded with the Nobel Prize, two generations of long baseline experiments had been setup to further study neutrino oscillations. The first generation experiments, K2K in Japan, Minos in the States and Opera in Europe, focused in confirming the Super-Kamiokande result, improving the precision with which oscillation parameters had been measured and demonstrating the ντ appearance process. Second generation experiments, T2K in Japan and very recently NOνA in the States, went further, being optimized to look for genuine three neutrino phenomena like non-zero values of θ13 and first glimpses to leptonic CP violation (LCPV) and neutrino mass ordering (NMO). The discovery of leptonic CP violation will require third generation setups, at the moment two strong proposals are ongoing, Dune in the States and Hyper-Kamiokande in Japan. This review will focus a little more in these future initiatives.

  20. Biofuels Baseline 2008

    Energy Technology Data Exchange (ETDEWEB)

    Hamelinck, C.; Koper, M.; Berndes, G.; Englund, O.; Diaz-Chavez, R.; Kunen, E.; Walden, D.

    2011-10-15

    The European Union is promoting the use of biofuels and other renewable energy in transport. In April 2009, the Renewable Energy Directive (2009/28/EC) was adopted that set a 10% target for renewable energy in transport in 2020. The directive sets several requirements to the sustainability of biofuels marketed in the frame of the Directive. The Commission is required to report to the European Parliament on a regular basis on a range of sustainability impacts resulting from the use of biofuels in the EU. This report serves as a baseline of information for regular monitoring on the impacts of the Directive. Chapter 2 discusses the EU biofuels market, the production and consumption of biofuels and international trade. It is derived where the feedstock for EU consumed biofuels originally come from. Chapter 3 discusses the biofuel policy framework in the EU and major third countries of supply. It looks at various policy aspects that are relevant to comply with the EU sustainability requirements. Chapter 4 discusses the environmental and social sustainability aspects associated with EU biofuels and their feedstock. Chapter 5 discusses the macro-economic effects that indirectly result from increased EU biofuels consumption, on commodity prices and land use. Chapter 6 presents country factsheets for main third countries that supplied biofuels to the EU market in 2008.

  1. Daily baseline skin care in the prevention, treatment, and supportive care of skin toxicity in oncology patients: recommendations from a multinational expert panel

    Directory of Open Access Journals (Sweden)

    Bensadoun RJ

    2013-12-01

    Full Text Available René-Jean Bensadoun,1 Phillipe Humbert,2 Jean Krutman,3 Thomas Luger,4 Raoul Triller,5 André Rougier,6 Sophie Seite,6 Brigitte Dreno71Department of Radiation Oncology, CHU Poitiers, Poitiers Cedex, 2Department of Dermatology, University Hospital of Besançon, Besançon, France; 3IUF-Leibniz Research Institute for Environmental Medicine, Heinrich-Heine University, Düsseldorf, 4Department of Dermatology, University of Münster, Münster, Germany; 5Centre of Dermatology, Hertford British Hospital, Levallois-Perret, 6La Roche-Posay Laboratoire Pharmaceutique, Asnières, 7Department of Cancero-Dermatology, Hôtel Dieu, CHU Nantes, FranceAbstract: Skin reactions due to radiotherapy and chemotherapy are a significant problem for an important number of cancer patients. While effective for treating cancer, they disturb cutaneous barrier function, causing a reaction soon after initiation of treatment that impacts patient quality of life. Managing these symptoms with cosmetics and nonpharmaceutical skin care products for camouflage or personal hygiene may be important for increasing patient self-esteem. However, inappropriate product choice or use could worsen side effects. Although recommendations exist for the pharmaceutical treatment of skin reactions, there are no recommendations for the choice or use of dermatologic skin care products for oncology patients. The present guidelines were developed by a board of European experts in dermatology and oncology to provide cancer care professionals with guidance for the appropriate use of non-pharmaceutical, dermocosmetic skin care management of cutaneous toxicities associated with radiotherapy and systemic chemotherapy, including epidermal growth factor inhibitors and monoclonal antibodies. The experts hope that these recommendations will improve the management of cutaneous side effects and hence quality of life for oncology patients.Keywords: skin care, cosmetic, dermatological toxicity, folliculitis

  2. Adherence to Plasmodium vivax malaria treatment in the Brazilian Amazon Region

    Directory of Open Access Journals (Sweden)

    Pereira Elza A

    2011-12-01

    Full Text Available Abstract Background Patients' adherence to malaria treatment is an important factor in determining the therapeutic response to anti-malarial drugs. It contributes to the patient's complete recovery and prevents the emergence of parasite resistance to anti-malarial drugs. In Brazil, the low compliance with malaria treatment probably explains the large number of Plasmodium vivax malaria relapses observed in the past years. The goal of this study was to estimate the proportion of patients adhering to the P. vivax malaria treatment with chloroquine + primaquine in the dosages recommended by the Brazilian Ministry of Health. Methods Patients who were being treated for P. vivax malaria with chloroquine plus primaquine were eligible for the study. On the seventh day of taking primaquine, they were visited at their home and were interviewed. The patients were classified as probably adherent, if they reported having taken all the medication as prescribed, in the correct period of time and dosage, and had no medication tablets remaining; probably non-adherent, if they reported not having taken the medication, in the correct period of time and dosage, and did not show any remaining tablets; and certainly non-adherent, if they showed any remaining medication tablets. Results 242 of the 280 patients reported having correctly followed the prescribed instructions and represented a treatment adherence frequency (CI95% of 86.4% (81.7%-90.1%. Of the 38 patients who did not follow the recommendations, 27 (9.6% were still taking the medication on the day of the interview and, therefore, still had primaquine tablets left in the blister pack. These patients were then classified as certainly non-adherent to treatment. Although 11 patients did not show any tablets left, they reported incorrect use of the prescribed therapy regimen and were considered as probably non-adherent to treatment. Conclusions Compliance with the P. vivax malaria treatment is a characteristic of

  3. Do baseline Cereblon gene expression and IL-6 receptor expression determine the response to thalidomide-dexamethasone treatment in multiple myeloma patients?

    Science.gov (United States)

    Bedewy, Ahmed M L; El-Maghraby, Shereen M

    2014-01-01

    Immunomodulatory drugs (IMiDs) are key components of treatment for hematologic malignancies, especially multiple myeloma (MM). Cereblon (CRBN) expression was described to be essential for the activity of thalidomide. Furthermore, IMiD binding to CRBN is cytotoxic to multiple myeloma cells and absence of CRBN confers IMiDs resistance. Interleukin-6 (IL-6) is a potent pleiotropic cytokine that regulates plasma cell (PC) growth via the IL-6 receptor (IL-6R). IL-6/IL-6R autocrine activity is implicated in the development and progression of cancers including cervical cancer, prostate cancer, and multiple myeloma. The aim of the study was to evaluate CRBN and IL-6R expressions and their impact on clinical efficacy of dexamethasone-thalidomide therapy in multiple myeloma (MM) patients, in addition to their association with other clinical and prognostic parameters. Forty-six newly diagnosed MM patients were enrolled in the study. We measured CRBN expression prior to therapy initiation by real-time polymerase chain reaction in 46 bone marrow (BM) aspiration samples of patients and controls. In addition, IL-6R expression was evaluated on BM biopsies of patients and controls by immunohistochemistry (IHC). Twenty-eight males (60.9%) and 18 females (39.1%) were enrolled. The mean age was 65.11 ± 7.3 yr (range 39-77 yr). Median CRBN expression in 46 BM samples of MM patients was significantly higher than in controls (P CRBN expression. IL-6R expression was significantly higher in patients than in controls. IL-6R expression was significantly associated with response to treatment (P CRBN expression (P = 0.001).In conclusion, CRBN expression may provide a biomarker to predict response to IMiD in patients with MM and its high expression can serve as a marker of good prognosis. Strong IL-6R expression is associated with poor response to therapy in multiple myeloma patients and may be used as a prognostic marker.

  4. Anti-malarial drug quality in Lagos and Accra - a comparison of various quality assessments

    OpenAIRE

    2010-01-01

    Abstract Background Two major cities in West Africa, Accra, the capital of Ghana, and Lagos, the largest city of Nigeria, have significant problems with substandard pharmaceuticals. Both have actively combated the problem in recent years, particularly by screening products on the market using the Global Pharma Health Fund e.V. Minilab® protocol. Random sampling of medicines from the two cities at least twice over the past 30 months allows a tentative assessment of whether improvements in drug...

  5. Anti-malarial activity of a non-piperidine library of next-generation quinoline methanols

    Directory of Open Access Journals (Sweden)

    Melendez Victor

    2010-02-01

    Full Text Available Abstract Background The clinical utility for mefloquine has been eroded due to its association with adverse neurological effects. Better-tolerated alternatives are required. The objective of the present study was the identification of lead compounds that are as effective as mefloquine, but exhibit physiochemical properties likely to render them less susceptible to passage across the blood-brain barrier. Methods A library of drug-like non-piperidine analogs of mefloquine was synthesized. These compounds are diverse in structure and physiochemical properties. They were screened in appropriate in vitro assays and evaluated in terms of their potential as lead compounds. The correlation of specific structural attributes and physiochemical properties with activity was assessed. Results The most potent analogs were low molecular weight unconjugated secondary amines with no heteroatoms in their side-chains. However, these compounds were more metabolically labile and permeable than mefloquine. In terms of physiochemical properties, lower polar surface area, lower molecular weight, more freely rotatable bonds and fewer H-bond acceptors were associated with greater potency. There was no such relationship between activity and LogP, LogD or the number of hydrogen bond donors (HBDs. The addition of an H-bond donor to the side-chain yielded a series of active diamines, which were as metabolically stable as mefloquine but showed reduced permeability. Conclusions A drug-like library of non-piperidine analogs of mefloquine was synthesized. From amongst this library an active lead series of less permeable, but metabolically stable, diamines was identified.

  6. The molecular evolution of four anti-malarial immune genes in the Anopheles gambiae species complex

    OpenAIRE

    Simard Frederic; Antonio-Nkondjio Christophe; Awono-Ambene Parfait H; Marshall Jonathon C; Slotman Michel A; Parmakelis Aristeidis; Caccone Adalgisa; Powell Jeffrey R

    2008-01-01

    Abstract Background If the insect innate immune system is to be used as a potential blocking step in transmission of malaria, then it will require targeting one or a few genes with highest relevance and ease of manipulation. The problem is to identify and manipulate those of most importance to malaria infection without the risk of decreasing the mosquito's ability to stave off infections by microbes in general. Molecular evolution methodologies and concepts can help identify such genes. Withi...

  7. Seasonal distribution of anti-malarial drug resistance alleles on the island of Sumba, Indonesia

    NARCIS (Netherlands)

    Asih, P.B.; Rogers, W.O.; Susanti, A.I.; Rahmat, A.; Rozi, I.E.; Kusumaningtyas, M.A.; Dewi, R.M.; Coutrier, F.N.; Sutamihardja, A.; Ven, A.J.A.M. van der; Sauerwein, R.W.; Syafruddin, D.

    2009-01-01

    BACKGROUND: Drug resistant malaria poses an increasing public health problem in Indonesia, especially eastern Indonesia, where malaria is highly endemic. Widespread chloroquine (CQ) resistance and increasing sulphadoxine-pyrimethamine (SP) resistance prompted Indonesia to adopt artemisinin-based com

  8. Retail sector distribution chains for malaria treatment in the developing world: a review of the literature

    Directory of Open Access Journals (Sweden)

    Hanson Kara G

    2010-02-01

    Full Text Available Abstract Background In many low-income countries, the retail sector plays an important role in the treatment of malaria and is increasingly being considered as a channel for improving medicine availability. Retailers are the last link in a distribution chain and their supply sources are likely to have an important influence on the availability, quality and price of malaria treatment. This article presents the findings of a systematic literature review on the retail sector distribution chain for malaria treatment in low and middle-income countries. Methods Publication databases were searched using key terms relevant to the distribution chain serving all types of anti-malarial retailers. Organizations involved in malaria treatment and distribution chain related activities were contacted to identify unpublished studies. Results A total of 32 references distributed across 12 developing countries were identified. The distribution chain had a pyramid shape with numerous suppliers at the bottom and fewer at the top. The chain supplying rural and less-formal outlets was made of more levels than that serving urban and more formal outlets. Wholesale markets tended to be relatively concentrated, especially at the top of the chain where few importers accounted for most of the anti-malarial volumes sold. Wholesale price mark-ups varied across chain levels, ranging from 27% to 99% at the top of the chain, 8% at intermediate level (one study only and 2% to 67% at the level supplying retailers directly. Retail mark-ups tended to be higher, and varied across outlet types, ranging from 3% to 566% in pharmacies, 29% to 669% in drug shops and 100% to 233% in general shops. Information on pricing determinants was very limited. Conclusions Evidence on the distribution chain for retail sector malaria treatment was mainly descriptive and lacked representative data on a national scale. These are important limitations in the advent of the Affordable Medicine Facility for

  9. Reviewing the literature on access to prompt and effective malaria treatment in Kenya: implications for meeting the Abuja targets

    Directory of Open Access Journals (Sweden)

    Tetteh Gladys

    2009-10-01

    Full Text Available Abstract Background Effective case management is central to reducing malaria mortality and morbidity worldwide, but only a minority of those affected by malaria, have access to prompt effective treatment. In Kenya, the Division of Malaria Control is committed to ensuring that 80 percent of childhood fevers are treated with effective anti-malarial medicines within 24 hours of fever onset, but this target is largely unmet. This review aimed to document evidence on access to effective malaria treatment in Kenya, identify factors that influence access, and make recommendations on how to improve prompt access to effective malaria treatment. Since treatment-seeking patterns for malaria are similar in many settings in sub-Saharan Africa, the findings presented in this review have important lessons for other malaria endemic countries. Methods Internet searches were conducted in PUBMED (MEDLINE and HINARI databases using specific search terms and strategies. Grey literature was obtained by soliciting reports from individual researchers working in the treatment-seeking field, from websites of major organizations involved in malaria control and from international reports. Results The review indicated that malaria treatment-seeking occurs mostly in the informal sector; that most fevers are treated, but treatment is often ineffective. Irrational drug use was identified as a problem in most studies, but determinants of this behaviour were not documented. Availability of non-recommended medicines over-the-counter and the presence of substandard anti-malarials in the market are well documented. Demand side determinants of access include perception of illness causes, severity and timing of treatment, perceptions of treatment efficacy, simplicity of regimens and ability to pay. Supply side determinants include distance to health facilities, availability of medicines, prescribing and dispensing practices and quality of medicines. Policy level factors are around

  10. Monitoring fever treatment behaviour and equitable access to effective medicines in the context of initiatives to improve ACT access: baseline results and implications for programming in six African countries

    Directory of Open Access Journals (Sweden)

    Littrell Megan

    2011-10-01

    Full Text Available Abstract Background Access to artemisinin-based combination therapy (ACT remains limited in high malaria-burden countries, and there are concerns that the poorest people are particularly disadvantaged. This paper presents new evidence on household treatment-seeking behaviour in six African countries. These data provide a baseline for monitoring interventions to increase ACT coverage, such as the Affordable Medicines Facility for malaria (AMFm. Methods Nationally representative household surveys were conducted in Benin, the Democratic Republic of Congo (DRC, Madagascar, Nigeria, Uganda and Zambia between 2008 and 2010. Caregivers responded to questions about management of recent fevers in children under five. Treatment indicators were tabulated across countries, and differences in case management provided by the public versus private sector were examined using chi-square tests. Logistic regression was used to test for association between socioeconomic status and 1 malaria blood testing, and 2 ACT treatment. Results Fever treatment with an ACT is low in Benin (10%, the DRC (5%, Madagascar (3% and Nigeria (5%, but higher in Uganda (21% and Zambia (21%. The wealthiest children are significantly more likely to receive ACT compared to the poorest children in Benin (OR = 2.68, 95% CI = 1.12-6.42; the DRC (OR = 2.18, 95% CI = 1.12-4.24; Madagascar (OR = 5.37, 95% CI = 1.58-18.24; and Nigeria (OR = 6.59, 95% CI = 2.73-15.89. Most caregivers seek treatment outside of the home, and private sector outlets are commonly the sole external source of treatment (except in Zambia. However, children treated in the public sector are significantly more likely to receive ACT treatment than those treated in the private sector (except in Madagascar. Nonetheless, levels of testing and ACT treatment in the public sector are low. Few caregivers name the national first-line drug as most effective for treating malaria in Madagascar (2%, the DRC (2%, Nigeria (4% and Benin (10

  11. Paricalcitol versus cinacalcet plus low-dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: study design and baseline characteristics of the IMPACT SHPT study

    Science.gov (United States)

    Martin, Kevin J.; Cozzolino, Mario; Goldsmith, David; Sharma, Amit; Khan, Samina; Dumas, Emily; Amdahl, Michael; Marx, Steven; Audhya, Paul

    2012-01-01

    Background. Paricalcitol and cinacalcet are common therapies for patients on haemodialysis with secondary hyperparathyroidism (SHPT). We conducted a multi-centre study in 12 countries to compare the safety and efficacy of paricalcitol and cinacalcet for the treatment of SHPT. Methods. Patients aged ≥18 years with Stage 5 chronic kidney disease receiving maintenance haemodialysis and with intact parathyroid hormone (iPTH) 300–800 pg/mL, calcium 8.4–10.0 mg/dL (2.09–2.49 mmol/L) and phosphorus ≤6.5 mg/dL (2.09 mmol/L) were randomized within two strata defined by the mode of paricalcitol administration to treatment with paricalcitol- (intra-venous, US and Russian sites, IV stratum; oral, non-US and non-Russian sites, oral stratum) or cinacalcet-centred therapy. The primary endpoint is the proportion of patients in each treatment group who achieve a mean iPTH value of 150–300 pg/mL during Weeks 21–28 of treatment. Assuming efficacy response rates of 36 and 66% for cinacalcet and paricalcitol, respectively, and a 20% discontinuation rate, 124 subjects in each stratum were estimated to provide 81% power to detect a 30% absolute difference in the primary endpoint. Results. Of 746 patients screened, 272 (mean age, 63 years; mean iPTH, 509 pg/mL) were randomized. Mean duration of haemodialysis at baseline was 3.7 years. Comorbidities included hypertension (90.4%), Type 2 diabetes (40.4%), congestive heart failure (17.3%), coronary artery disease (34.6%) and gastrointestinal disorders (75%). Conclusions. The study participants are representative of a multinational cohort of patients on haemodialysis with elevated iPTH. The study results will provide valuable information on the best available treatment of SHPT in patients on haemodialysis. PMID:21931122

  12. Hanford Site technical baseline database

    Energy Technology Data Exchange (ETDEWEB)

    Porter, P.E., Westinghouse Hanford

    1996-05-10

    This document includes a cassette tape that contains the Hanford specific files that make up the Hanford Site Technical Baseline Database as of May 10, 1996. The cassette tape also includes the delta files that delineate the differences between this revision and revision 3 (April 10, 1996) of the Hanford Site Technical Baseline Database.

  13. Hanford Site technical baseline database

    Energy Technology Data Exchange (ETDEWEB)

    Porter, P.E.

    1996-09-30

    This document includes a cassette tape that contains the Hanford specific files that make up the Hanford Site Technical Baseline Database as of September 30, 1996. The cassette tape also includes the delta files that dellinate the differences between this revision and revision 4 (May 10, 1996) of the Hanford Site Technical Baseline Database.

  14. Plutonium Immobilization Project Baseline Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Ebbinghaus, B.

    1999-02-01

    A key milestone for the Immobilization Project (AOP Milestone 3.2a) in Fiscal Year 1998 (FY98) is the definition of the baseline composition or formulation for the plutonium ceramic form. The baseline formulation for the plutonium ceramic product must be finalized before the repository- and plant-related process specifications can be determined. The baseline formulation that is currently specified is given in Table 1.1. In addition to the baseline formulation specification, this report provides specifications for two alternative formulations, related compositional specifications (e.g., precursor compositions and mixing recipes), and other preliminary form and process specifications that are linked to the baseline formulation. The preliminary specifications, when finalized, are not expected to vary tremendously from the preliminary values given.

  15. Oscillation Baselining and Analysis Tool

    Energy Technology Data Exchange (ETDEWEB)

    2017-03-27

    PNNL developed a new tool for oscillation analysis and baselining. This tool has been developed under a new DOE Grid Modernization Laboratory Consortium (GMLC) Project (GM0072 - “Suite of open-source applications and models for advanced synchrophasor analysis”) and it is based on the open platform for PMU analysis. The Oscillation Baselining and Analysis Tool (OBAT) performs the oscillation analysis and identifies modes of oscillations (frequency, damping, energy, and shape). The tool also does oscillation event baselining (fining correlation between oscillations characteristics and system operating conditions).

  16. 324 Building Baseline Radiological Characterization

    Energy Technology Data Exchange (ETDEWEB)

    R.J. Reeder, J.C. Cooper

    2010-06-24

    This report documents the analysis of radiological data collected as part of the characterization study performed in 1998. The study was performed to create a baseline of the radiological conditions in the 324 Building.

  17. Quivira NWR biological baseline data

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This dataset is biological baseline data for Quivira National Wildlife Refuge as of January 2016. It contains data on species found on the refuge, when and where...

  18. Which method better evaluates the molecular response in newly diagnosed chronic phase chronic myeloid leukemia patients with imatinib treatment, BCR-ABL(IS) or log reduction from the baseline level?

    Science.gov (United States)

    Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Li, Jin-Lan; Li, Ling-Di; Zhu, Hong-Hu; Lai, Yue-Yun; Lu, Xi-Jing; Liu, Yan-Rong; Jiang, Bin; Huang, Xiao-Jun

    2013-09-01

    The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all Plog reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤ 10%(IS) and ≥ 1 log reduction at 3 months and ≤ 1%(IS) at 6 months were significantly associated with PFS (P=0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories.

  19. Modelling malaria treatment practices in Bangladesh using spatial statistics

    Directory of Open Access Journals (Sweden)

    Haque Ubydul

    2012-03-01

    Full Text Available Abstract Background Malaria treatment-seeking practices vary worldwide and Bangladesh is no exception. Individuals from 88 villages in Rajasthali were asked about their treatment-seeking practices. A portion of these households preferred malaria treatment from the National Control Programme, but still a large number of households continued to use drug vendors and approximately one fourth of the individuals surveyed relied exclusively on non-control programme treatments. The risks of low-control programme usage include incomplete malaria treatment, possible misuse of anti-malarial drugs, and an increased potential for drug resistance. Methods The spatial patterns of treatment-seeking practices were first examined using hot-spot analysis (Local Getis-Ord Gi statistic and then modelled using regression. Ordinary least squares (OLS regression identified key factors explaining more than 80% of the variation in control programme and vendor treatment preferences. Geographically weighted regression (GWR was then used to assess where each factor was a strong predictor of treatment-seeking preferences. Results Several factors including tribal affiliation, housing materials, household densities, education levels, and proximity to the regional urban centre, were found to be effective predictors of malaria treatment-seeking preferences. The predictive strength of each of these factors, however, varied across the study area. While education, for example, was a strong predictor in some villages, it was less important for predicting treatment-seeking outcomes in other villages. Conclusion Understanding where each factor is a strong predictor of treatment-seeking outcomes may help in planning targeted interventions aimed at increasing control programme usage. Suggested strategies include providing additional training for the Building Resources across Communities (BRAC health workers, implementing educational programmes, and addressing economic factors.

  20. Artemisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy!

    Science.gov (United States)

    Mutabingwa, T K

    2005-09-01

    within funding agencies might improve the situation. Increased interest in drug development together with the public and private sector partnership have led to new anti-malarials, some less expensive and therefore affordable by poor malaria endemic countries. Dihydroartemisinin-piperaquine (Artekin) has a cost advantage over other ACTs (USD 1 for an adult treatment) making it a potential best candidate for deployment in Africa. Part of available funds should be invested into capacity building and strengthening (personnel, resources and infrastructure) of institutions in malaria endemic countries. This will create enabling environment and a critical mass of scientists and public health experts to spearhead ACT policy implementation. Active involvement of scientists from malaria endemic countries in recent International Scientific Forums like the Malaria in Pregnancy Working Group and the Consortium on ACT Implementation is the best way forward to emulate.

  1. Diagnosis and treatment based on quantitative PCR after controlled human malaria infection

    Directory of Open Access Journals (Sweden)

    Jona Walk

    2016-08-01

    Full Text Available Abstract Background Controlled human malaria infection (CHMI has become well-established in the evaluation of drugs and vaccines. Anti-malarial treatment is usually initiated when thick blood smears are positive by microscopy. This study explores the effects of using the more sensitive qPCR as the primary diagnostic test. Methods 1691 diagnostic blood samples were analysed by microscopy and qPCR from 115 volunteers (55 malaria naïve and 60 having received chemoprophylaxis and sporozoite immunization who were challenged by five mosquitoes infected with Plasmodium falciparum sporozoites of the NF54 strain. Results Retrospective analysis of different qPCR criteria for diagnosis and treatment, showed that once daily qPCR (threshold 100 parasites/ml had 99 % sensitivity and 100 % specificity, and shortened the median prepatent period from 10.5 to 7.0 days after CHMI when compared to twice daily measurement of thick blood smears (threshold 4000 parasites/ml. This is expected to result in a 78 % decrease of adverse events before initiation of treatment in future studies. Trial outcome related to infection and protective efficacy remained unchanged. Conclusion The use of qPCR as the primary diagnostic test in CHMI decreases symptoms as well as parasitaemia while obviating the need for twice daily follow-up. The implementation improves safety while reducing the clinical burden and costs without compromising the evaluation of protective efficacy.

  2. Baseline Removal From EMG Recordings

    Science.gov (United States)

    2007-11-02

    a time-varying baseline contamination. Acknowledgements: Work funded by the Departamento de Salud del Gobierno de Navarrra and by a Spanish MEC...Name(s) and Address(es) Departamento de Ingenieria Electra y Electronica Universidad Publica de Navarra Pamplona, Spain Performing Organization Report

  3. Use of behavioral economics and social psychology to improve treatment of acute respiratory infections (BEARI): rationale and design of a cluster randomized controlled trial [1RC4AG039115-01] - study protocol and baseline practice and provider characteristics

    Science.gov (United States)

    2013-01-01

    Background Inappropriate antibiotic prescribing for nonbacterial infections leads to increases in the costs of care, antibiotic resistance among bacteria, and adverse drug events. Acute respiratory infections (ARIs) are the most common reason for inappropriate antibiotic use. Most prior efforts to decrease inappropriate antibiotic prescribing for ARIs (e.g., educational or informational interventions) have relied on the implicit assumption that clinicians inappropriately prescribe antibiotics because they are unaware of guideline recommendations for ARIs. If lack of guideline awareness is not the reason for inappropriate prescribing, educational interventions may have limited impact on prescribing rates. Instead, interventions that apply social psychological and behavioral economic principles may be more effective in deterring inappropriate antibiotic prescribing for ARIs by well-informed clinicians. Methods/design The Application of Behavioral Economics to Improve the Treatment of Acute Respiratory Infections (BEARI) Trial is a multisite, cluster-randomized controlled trial with practice as the unit of randomization. The primary aim is to test the ability of three interventions based on behavioral economic principles to reduce the rate of inappropriate antibiotic prescribing for ARIs. We randomized practices in a 2 × 2 × 2 factorial design to receive up to three interventions for non-antibiotic-appropriate diagnoses: 1) Accountable Justifications: When prescribing an antibiotic for an ARI, clinicians are prompted to record an explicit justification that appears in the patient electronic health record; 2) Suggested Alternatives: Through computerized clinical decision support, clinicians prescribing an antibiotic for an ARI receive a list of non-antibiotic treatment choices (including prescription options) prior to completing the antibiotic prescription; and 3) Peer Comparison: Each provider’s rate of inappropriate antibiotic prescribing relative to top

  4. Perceptions and Attitudes of Resident Doctors about Malaria Treatment as Per National Drug Policy on Malaria

    Directory of Open Access Journals (Sweden)

    Ghanshyam Ahir, D V Bala

    2012-01-01

    Full Text Available Background: The involvement of public and private health care providers in malaria treatment, particularly understanding their knowledge and practices will aid in devising strategies to increase the rational use of antimalarial drugs. They should be aware about rationale and implement national drug policy on malaria to prevent morbidity and mortality of malaria as well as development of antimalarial drug resistance. Therefore, a study was planned on the same issue among resident doctors of a tertiary care teaching hospital. Objective: To study the perceptions and attitudes of resident doctors regarding use of anti malarial drugs for treatment of all types of malaria cases in accordance with national drug policy on malaria-2010. Methodology: This cross-sectional study was conducted at tertiary care teaching hospital with sixty four (64 resident doctors of medicine (24, pediatrics (24 and obstetrics (16 departments with the help of pre tested; semi-structured questionnaire based on national drug policy on malaria-2010 from 15th July to 30th August 2010. Results: Only 12 (18.8% residents were aware about drug policy. Dose and duration and indication of primaquine was known to 21 (32.8% of resident doctors. Artesunate (49.2% and Arteether (16.9% were commonly prescribed in case of uncomplicated P.falciparum and P.vivax malaria. Conclusion: It was noticeable that knowledge and awareness regarding drug policy among resident doctors was unsatisfactory. Regular sensitization programme on malaria drug policy should be conducted.

  5. Mode S Baseline Radar Tracking.

    Science.gov (United States)

    1982-11-01

    range units and 20 azimuth units) overlaying the position of the beacon reports. In the cases analyzed where beacon reports were not radar reinforced ...82/53 j~ C ~ 7 C _ _ _ _ _ _ 4. Title end Su.btitle 5. Neget at. November 1982 MDDE S BASELINE RADAR TRACKIN4G 6. Poelin Orgeuianti.. Cede ACT-100...Ground Clutter 33 Mode S/ARTS III 100-Scan False Radar Track Summary 74 34 Percent Beacon Radar Reinforcement 77 vii INTRODUCTION PURPOSE. The purpose of

  6. The telmisartan renoprotective study from incipient nephropathy to overt nephropathy--rationale, study design, treatment plan and baseline characteristics of the incipient to overt: angiotensin II receptor blocker, telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study.

    Science.gov (United States)

    Makino, H; Haneda, M; Babazono, T; Moriya, T; Ito, S; Iwamoto, Y; Kawamori, R; Takeuchi, M; Katayama, S

    2005-01-01

    We planned the INNOVATION study to determine whether telmisartan, an angiotensin-2-receptor blocker, delays the progression of renal disease from incipient nephropathy to overt nephropathy in hypertensive or normotensive Japanese patients with type 2 diabetes mellitus. The INNOVATION study is a randomized, double-blind, placebo-controlled trial. Eligible patients must have incipient nephropathy (defined as a urinary albumin to creatinine ratio of 100-300 mg/g creatinine) and a serum creatinine concentration of 300 mg/g creatinine and 30% higher than the baseline on at least two consecutive visits). A total of 1855 patients have been enrolled from 160 study centres. In 527 randomized patients (28.4% of the enrolled patients), mean (SD) urinary albumin to creatinine ratio and serum creatinine concentration at baseline were 173.3 (47.2) mg/g creatinine and 0.78 (0.19) mg/dl. Sixty-eight per cent of the patients had hypertension at baseline. Mean (SD) systolic and diastolic blood pressures at baseline were 137.1 (14.6) and 77.5 (10.3) mmHg. The INNOVATION study will determine whether telmisartan, an angiotensin II receptor blocker, provides clinical benefits in hypertensive or normotensive patients with diabetes mellitus and diabetic nephropathy.

  7. The detection and treatment of Plasmodium falciparum malaria: Time for change

    Directory of Open Access Journals (Sweden)

    Nosten F

    2004-01-01

    Full Text Available In most countries where malaria is endemic, P. falciparum malaria is on the rise. This is primarily due to the spread of drug-resistant strains. Drug resistance is mediated by spontaneous changes in the parasite genome that allow resistant parasites to escape the action of the drugs. The spread of drug resistance increases the transmission of malaria parasites. The consequences for the populations at risk are profound both in terms of consequences for health and economy. In order to halt the progression of drug resistance, we need to change the way antimalarials are used. As in tuberculosis and HIV/AIDS, we must use a combination of drugs for the treatment of malaria. Taking into account the pharmacokinetic and pharmacodynamic properties of the various anti-malarial agents, artemisinin-based combination therapy (ACT seems to be the best option. This strategy should be used in conjunction with early diagnosis and appropriate vector control measures to achieve reduction in the emergence and spread of drug resistance.

  8. Long-Baseline Neutrino Experiments

    Science.gov (United States)

    Diwan, M. V.; Galymov, V.; Qian, X.; Rubbia, A.

    2016-10-01

    We review long-baseline neutrino experiments in which neutrinos are detected after traversing macroscopic distances. Over such distances neutrinos have been found to oscillate among flavor states. Experiments with solar, atmospheric, reactor, and accelerator neutrinos have resulted in a coherent picture of neutrino masses and mixing of the three known flavor states. We summarize the current best knowledge of neutrino parameters and phenomenology, with a focus on the evolution of the experimental technique. We proceed from the first evidence produced by astrophysical neutrino sources to the current open questions and the goals of future research.

  9. Long-Baseline Neutrino Experiments

    CERN Document Server

    Diwan, M V; Qian, X; Rubbia, A

    2016-01-01

    We review long-baseline neutrino experiments in which neutrinos are detected after traversing macroscopic distances. Over such distances neutrinos have been found to oscillate among flavor states. Experiments with solar, atmospheric, reactor, and accelerator neutrinos have resulted in a coherent picture of neutrino masses and mixing of the three known flavor states. We will summarize the current best knowledge of neutrino parameters and phenomenology with our focus on the evolution of the experimental technique. We proceed from the first evidence produced by astrophysical neutrino sources to the current open questions and the goals of future research.

  10. Baseline LAW Glass Formulation Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, Albert A. [USDOE Office of River Protection, Richland, WA (United States); Mooers, Cavin [The Catholic University of America, Washington, DC (United States). Vitreous State Lab.; Bazemore, Gina [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Pegg, Ian L. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Hight, Kenneth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Lai, Shan Tao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Buechele, Andrew [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Rielley, Elizabeth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Gan, Hao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Muller, Isabelle S. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Cecil, Richard [The Catholic University of America, Washington, DC (United States). Vitreous State Lab

    2013-06-13

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements.

  11. The impact of intermittent preventive treatment with sulfadoxine-pyrimethamine on the prevalence of malaria parasitaemia in pregnancy.

    Science.gov (United States)

    Umeh, Uchenna Anthony; Obi, Samuel N; Onah, Hyacinth E; Ugwu, Emmanuel Onyebuchi V; Ajah, Leonard Ogbonna; Umeh, Chioma Roseline; Okafor, Innocent Igwebuike

    2012-07-01

    The Roll Back Malaria initiatives were introduced to ensure that 60% of pregnant women receive intermittent preventive anti-malarial treatment by the end of 2005 in an attempt to halve the mortality from malaria by 2010. Our aim was to determine the prevalence of asymptomatic malaria parasitaemia in pregnant women on intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) compared with a control group. This comparative study involved testing the peripheral blood of pregnant women on IPT with SP and a control group that did not receive SP for the malaria parasite upon registration and at 34 weeks gestational age. The levels of parasitaemia in the intervention group upon registration (4.9%) and at 34 weeks (63.9%) were not significantly different (P > 0.05) from that of the control group (10%) and at 34 weeks gestation (68.3%). IPT with SP during pregnancy did not significantly reduce the prevalence of the malaria parasitaemia among the pregnant women in our environment.

  12. FED baseline engineering studies report

    Energy Technology Data Exchange (ETDEWEB)

    Sager, P.H.

    1983-04-01

    Studies were carried out on the FED Baseline to improve design definition, establish feasibility, and reduce cost. Emphasis was placed on cost reduction, but significant feasibility concerns existed in several areas, and better design definition was required to establish feasibility and provide a better basis for cost estimates. Design definition and feasibility studies included the development of a labyrinth shield ring concept to prevent radiation streaming between the torus spool and the TF coil cryostat. The labyrinth shield concept which was developed reduced radiation streaming sufficiently to permit contact maintenance of the inboard EF coils. Various concepts of preventing arcing between adjacent shield sectors were also explored. It was concluded that installation of copper straps with molybdenum thermal radiation shields would provide the most reliable means of preventing arcing. Other design studies included torus spool electrical/structural concepts, test module shielding, torus seismic response, poloidal conditions in the magnets, disruption characteristics, and eddy current effects. These additional studies had no significant impact on cost but did confirm the feasibility of the basic FED Baseline concept.

  13. Pinellas Plant Environmental Baseline Report

    Energy Technology Data Exchange (ETDEWEB)

    1997-06-01

    The Pinellas Plant has been part of the Department of Energy`s (DOE) nuclear weapons complex since the plant opened in 1957. In March 1995, the DOE sold the Pinellas Plant to the Pinellas County Industry Council (PCIC). DOE has leased back a large portion of the plant site to facilitate transition to alternate use and safe shutdown. The current mission is to achieve a safe transition of the facility from defense production and prepare the site for alternative uses as a community resource for economic development. Toward that effort, the Pinellas Plant Environmental Baseline Report (EBR) discusses the current and past environmental conditions of the plant site. Information for the EBR is obtained from plant records. Historical process and chemical usage information for each area is reviewed during area characterizations.

  14. Integrated Baseline Review (IBR) Handbook

    Science.gov (United States)

    Fleming, Jon F.; Kehrer, Kristen C.

    2016-01-01

    The purpose of this handbook is intended to be a how-to guide to prepare for, conduct, and close-out an Integrated Baseline Review (IBR). It discusses the steps that should be considered, describes roles and responsibilities, tips for tailoring the IBR based on risk, cost, and need for management insight, and provides lessons learned from past IBRs. Appendices contain example documentation typically used in connection with an IBR. Note that these appendices are examples only, and should be tailored to meet the needs of individual projects and contracts. Following the guidance in this handbook will help customers and suppliers preparing for an IBR understand the expectations of the IBR, and ensure that the IBR meets the requirements for both in-house and contract efforts.

  15. Atlantic NAD 83 SLA Baseline Tangents

    Data.gov (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This data set contains baseline tangent lines in ArcGIS shapefile format for the BOEM Atlantic Region. Baseline tangent lines are typically bay or river closing...

  16. Atlantic NAD 83 SLA Baseline Points

    Data.gov (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This data set contains baseline points in ArcGIS shapefile format for the BOEM Atlantic Region. Baseline points are the discrete coordinate points along the...

  17. 2016 Annual Technology Baseline (ATB) - Webinar Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Wesley; Kurup, Parthiv; Hand, Maureen; Feldman, David; Sigrin, Benjamin; Lantz, Eric; Stehly, Tyler; Augustine, Chad; Turchi, Craig; Porro, Gian; O' Connor, Patrick; Waldoch, Connor

    2016-09-13

    This deck was presented for the 2016 Annual Technology Baseline Webinar. The presentation describes the Annual Technology Baseline, which is a compilation of current and future cost and performance data for electricity generation technologies.

  18. Diagnosis and treatment of malaria in peripheral health facilities in Uganda: findings from an area of low transmission in south-western Uganda

    Directory of Open Access Journals (Sweden)

    Clarke Siân

    2007-04-01

    Full Text Available Abstract Background Early recognition of symptoms and signs perceived as malaria are important for effective case management, as few laboratories are available at peripheral health facilities. The validity and reliability of clinical signs and symptoms used by health workers to diagnose malaria were assessed in an area of low transmission in south-western Uganda. Methods The study had two components: 1 passive case detection where all patients attending the out patient clininc with a febrile illness were included and 2 a longitudinal active malaria case detection survey was conducted in selected villages. A malaria case was defined as any slide-confirmed parasitaemia in a person with an axillary temperature ≥ 37.5°C or a history of fever within the last 24 hrs and no signs suggestive of other diseases. Results Cases of malaria were significantly more likely to report joint pains, headache, vomiting and abdominal pains. However, due to the low prevalence of malaria, the predictive values of these individual signs alone, or in combination, were poor. Only 24.8% of 1627 patients had malaria according to case definition and > 75% of patients were unnecessarily treated for malaria and few slide negative cases received alternative treatment. Conclusion In low-transmission areas, more attention needs to be paid to differential diagnosis of febrile illnesses In view of suggested changes in anti-malarial drug policy, introducing costly artemisinin combination therapy accurate, rapid diagnostic tools are necessary to target treatment to people in need.

  19. 2016 Annual Technology Baseline (ATB)

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Wesley; Kurup, Parthiv; Hand, Maureen; Feldman, David; Sigrin, Benjamin; Lantz, Eric; Stehly, Tyler; Augustine, Chad; Turchi, Craig; O' Connor, Patrick; Waldoch, Connor

    2016-09-01

    Consistent cost and performance data for various electricity generation technologies can be difficult to find and may change frequently for certain technologies. With the Annual Technology Baseline (ATB), National Renewable Energy Laboratory provides an organized and centralized dataset that was reviewed by internal and external experts. It uses the best information from the Department of Energy laboratory's renewable energy analysts and Energy Information Administration information for conventional technologies. The ATB will be updated annually in order to provide an up-to-date repository of current and future cost and performance data. Going forward, we plan to revise and refine the values using best available information. The ATB includes both a presentation with notes (PDF) and an associated Excel Workbook. The ATB includes the following electricity generation technologies: land-based wind; offshore wind; utility-scale solar PV; concentrating solar power; geothermal power; hydropower plants (upgrades to existing facilities, powering non-powered dams, and new stream-reach development); conventional coal; coal with carbon capture and sequestration; integrated gasification combined cycle coal; natural gas combustion turbines; natural gas combined cycle; conventional biopower. Nuclear laboratory's renewable energy analysts and Energy Information Administration information for conventional technologies. The ATB will be updated annually in order to provide an up-to-date repository of current and future cost and performance data. Going forward, we plan to revise and refine the values using best available information.

  20. Relationship between treatment-seeking behaviour and artemisinin drug quality in Ghana

    Directory of Open Access Journals (Sweden)

    Klein Eili Y

    2012-04-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is currently the recommended first-line treatment for uncomplicated malaria infections. However, a significant proportion of ACT is assumed to be of poor quality, particularly in Africa. In addition, little is known about how treatment-seeking behaviour of individuals or drug price is associated with drug quality. Methods Caregivers of children less than 5 years of age were interviewed on their knowledge of malaria and their choices for treatment. Artemisinin drugs were then purchased from sellers that caregivers preferred or had previously patronized. The active ingredients were quantified by nuclear magnetic resonance spectroscopy. Results A negative relationship was anticipated between the education level of caregivers and the quality of anti-malarial drugs purchased. However, of the 33 drugs collected from 16 different shops, only one contained less than 80% of its purported active ingredient, and most drugs were within 90% of their listed amounts. No link was found between drug quality and price. Nonetheless, while ACT is the recommended first-line treatment in Ghana, 21% of the drugs collected were artemisinin monotherapy, and 27% of the ACT was not co-formulated. Among caregivers, higher education was found to be associated with both an increased likelihood of seeking treatment in a clinic first, as opposed to visiting drug shops or using herbal remedies, and with purchasing drugs from licensed sellers. Conclusion Surprisingly, drug quality was found to be uniformly high and thus no significant relationship between price, treatment-seeking behaviour and the content of the active ingredients was observed. However, artemisinin monotherapy, which the WHO considers inappropriate therapy, was still widely available in Ghana in 2010. Monotherapy was more likely to be available in unlicensed vendors where less-educated caregivers generally shopped. This linkage between education

  1. Treatment of imported severe malaria with artesunate instead of quinine--more evidence needed?

    NARCIS (Netherlands)

    Cramer, J.P.; López-Vélez, R.; Burchard, G.D.; Grobusch, M.P.; de Vries, P.J.

    2011-01-01

    Rapid and fast acting anti-malarials are essential to treat severe malaria. Quinine has been the only option for parenteral therapy until recently. While current evidence shows that intravenous artesunate is more effective than quinine in treating severe malaria in endemic countries, some questions

  2. The molecular evolution of four anti-malarial immune genes in the Anopheles gambiae species complex - art. no. 79

    OpenAIRE

    Parmakelis, A.; Slotman, M. A.; Marshall, J. C.; Awono Ambene, P. H.; Antonio Nkondjio, C.; Simard, Frédéric; Caccone, A; Powell, J. R.

    2008-01-01

    Background: If the insect innate immune system is to be used as a potential blocking step in transmission of malaria, then it will require targeting one or a few genes with highest relevance and ease of manipulation. The problem is to identify and manipulate those of most importance to malaria infection without the risk of decreasing the mosquito's ability to stave off infections by microbes in general. Molecular evolution methodologies and concepts can help identify such genes. Within the se...

  3. Nature's Chiral Catalyst and Anti-Malarial Agent: Isolation and Structure Elucidation of Cinchonine and Quinine from "Cinchona calisaya"

    Science.gov (United States)

    Carroll, Anne-Marie; Kavanagh, David J.; McGovern, Fiona P.; Reilly, Joe W.; Walsh, John J.

    2012-01-01

    Nature is a well-recognized source of compounds of interest, but access is often an issue. One pertinent example is the cinchona alkaloids from the bark of "Cinchona calisaya." In this experiment, students at the third-year undergraduate level undertake the selective isolation and characterization of two of the four main alkaloids present in the…

  4. Crystal structures of multidrug-resistant HIV-1 protease in complex with two potent anti-malarial compounds

    Energy Technology Data Exchange (ETDEWEB)

    Yedidi, Ravikiran S.; Liu, Zhigang; Wang, Yong; Brunzelle, Joseph S.; Kovari, Iulia A.; Woster, Patrick M.; Kovari, Ladislau C.; Gupta, Deepak (LECOM); (WSI); (NWU); (MUSC); (WSU)

    2012-06-19

    Two potent inhibitors (compounds 1 and 2) of malarial aspartyl protease, plasmepsin-II, were evaluated against wild type (NL4-3) and multidrug-resistant clinical isolate 769 (MDR) variants of human immunodeficiency virus type-1 (HIV-1) aspartyl protease. Enzyme inhibition assays showed that both 1 and 2 have better potency against NL4-3 than against MDR protease. Crystal structures of MDR protease in complex with 1 and 2 were solved and analyzed. Crystallographic analysis revealed that the MDR protease exhibits a typical wide-open conformation of the flaps (Gly48 to Gly52) causing an overall expansion in the active site cavity, which, in turn caused unstable binding of the inhibitors. Due to the expansion of the active site cavity, both compounds showed loss of direct contacts with the MDR protease compared to the docking models of NL4-3. Multiple water molecules showed a rich network of hydrogen bonds contributing to the stability of the ligand binding in the distorted binding pockets of the MDR protease in both crystal structures. Docking analysis of 1 and 2 showed a decrease in the binding affinity for both compounds against MDR supporting our structure-function studies. Thus, compounds 1 and 2 show promising inhibitory activity against HIV-1 protease variants and hence are good candidates for further development to enhance their potency against NL4-3 as well as MDR HIV-1 protease variants.

  5. Comparison of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients - baseline characteristics, treatment adherence, and development of clinical variables during three years of anti-TNF therapy in clinical practice

    DEFF Research Database (Denmark)

    Wallman, Johan K; Kapetanovic, Meliha C; Petersson, Ingemar F

    2015-01-01

    BACKGROUND: The relationship between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) is currently debated. Using observational data from the South Swedish Arthritis Treatment Group register, we thus aimed to compare clinical development and treatment adherence...

  6. The impact of text message reminders on adherence to antimalarial treatment in northern Ghana: a randomized trial.

    Directory of Open Access Journals (Sweden)

    Julia R G Raifman

    Full Text Available BACKGROUND: Low rates of adherence to artemisinin-based combination therapy (ACT regimens increase the risk of treatment failure and may lead to drug resistance, threatening the sustainability of current anti-malarial efforts. We assessed the impact of text message reminders on adherence to ACT regimens. METHODS: Health workers at hospitals, clinics, pharmacies, and other stationary ACT distributors in Tamale, Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment. The messaging system automatically randomized self-enrolled individuals to the control group or the treatment group with equal probability; those in the treatment group were further randomly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals. The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation. We estimated the impact of the messages on treatment completion using logistic regression. RESULTS: 1140 individuals enrolled in both the study and the text reminder system. Among individuals in the control group, 61.5% took the full course of treatment. The simple text message reminders increased the odds of adherence (adjusted OR 1.45, 95% CI [1.03 to 2.04], p-value 0.028. Receiving an additional message did not result in a significant change in adherence (adjusted OR 0.77, 95% CI [0.50 to 1.20], p-value 0.252. CONCLUSION: The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment. Further research is needed to develop the most effective text message content and frequency. TRIAL REGISTRATION: ClinicalTrials.gov NCT01722734.

  7. Baseline survey of pregnant women 's knowledge of treat-ment to prevent mother-to-child human immuno-deficien-cy virus transmission in a resource limited setting

    Institute of Scientific and Technical Information of China (English)

    Stephen Onwere; Obioha Okoro; Bright Chigbu; Chuks Kamanu; Christian Aluka; Paul Feyi-Wa-boso

    2008-01-01

    Despite continuing advances in scientific knowledge about treatments to prevent mother-to-child (MTCT)of the human immune deficiency virus (HIV),there is a paucity of data on pregnant women's knowledge of treat-ments to prevent MTCT of HIV in Aba,South Eastern Nigeria.We investigated pregnant women's knowledge of the availability of treatments to prevent MTCT of HIV in the low resourced setting of Aba town in South Eastern Nigeria.A descriptive study involving 100 consecutive and consenting patients at the antenatal clinic of Abia State University Teaching Hospital (ABSUTH),Aba,South Eastern Nigeria over the period 1st November, 2007 to 30th November,2007.Using a structured questionnaire,the respondents'sociodemographic data were obtained as well as their knowledge of the availability of treatments to prevent mother to child HIV transmission in pregnant women and self-reported data on their having ever tested for HIV.Knowledge regarding availability of treatment to prevent mother to child transmission of HIV was good as 95% of the respondents were aware that such treatment was available.Knowledge that treatment is available to help someone infected by HIV to live longer was also good as 96% of the respondents were aware of the availability of such treatment.Seventy one percent of the respondents had ever tested for HIV.The levels of knowledge regarding the availability of treatment to prevent mother to child HIV transmission and to help someone infected with HIV are good.Thus, utilization of anti-retroviral prophylaxis amongst HIV infected pregnant women in this community would be ex-pected to be high if the drugs were available.This will reduce the impact of HIV,especially in children.

  8. Cost comparison of microscopy vs. empiric treatment for malaria in southwestern nigeria: a prospective study

    Directory of Open Access Journals (Sweden)

    Davidson Mario

    2010-12-01

    Full Text Available Abstract Background Presumptive treatment for malaria is common in resource-limited settings, yet controversial given the imprecision of clinical diagnosis. The researchers compared costs of diagnosis and drugs for two strategies: (1 empirical treatment of malaria via clinical diagnosis; and (2 empirical diagnosis followed by treatment only with Giemsa smear confirmation. Methods Patients with a diagnosis of clinical malaria were recruited from a mission/university teaching hospital in southwestern Nigeria. The patients underwent free Giemsa thick (diagnosis and thin (differentiation smears, but paid for all anti-malarial drugs. Clinical diagnosis was made on clinicians' judgments based on symptoms, including fever, diarrhoea, headache, and body aches. The paediatric regimen was artesunate (6-9 tablets of 3 mg/kg on day one and 1.5 mg/kg for the next four days plus amodiaquine (10 mg/kg day 1-2 and 5 mg/kg on day three in suspension. Adults were given two treatment options: option one (four and one-half 50 mg artesunate tablets on day one and nine tablets for the next four days, plus three 500 mg sulphadoxine/25 mg pyrimethamine tablets and option two (same artesunate regimen plus nine 200 mg tablets of amodiaquine at 10 mg/kg day 1-2 and 5 mg/kg on day three. The researchers calculated the costs of smears/drugs from standard hospital charges. Results Doctors diagnosed 304 patients (170 adults ages >16 years and 134 pediatric with clinical malaria, prescribing antimalarial drugs to all. Giemsa thick smears were positive in 115/304 (38%. The typical patient cost for a Giemsa smear was 550 Naira (US$3.74 in 2009. For children, the cost of testing all, but treating only Giemsa positives was N888 ($6.04/child; the cost of empiric treatment of all who were clinically diagnosed was lower, N660 ($4.49/child. For adults, the cost of testing all, but treating only Giemsa positives was N711 ($4.84/adult for treatment option one (artesunate and

  9. Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia

    Directory of Open Access Journals (Sweden)

    Bacha Ketema

    2011-03-01

    Full Text Available Abstract Background Chloroquine is an anti-malarial drug being used to treat Plasmodium vivax malaria cases in Ethiopia. However, emergence of chloroquine resistant strains of the parasite has challenged the current efficacy of the drug. Therefore, the aim of this study was to assess the effectiveness of chloroquine against P. vivax strains in one of the malaria endemic areas of Ethiopia, namely Halaba district, located in South Nations and Nationalities Peoples Region (SNNPR of South Ethiopia Results Among 87 malaria patients enrolled in the study, only 80 of them completed the 28-days follow-up. Seven of them dropped from the study for different reasons. Among those study participants that completed their follow-up, 69 were classified under the category of adequate clinical and parasitological response (ACPR. However, the remaining 11 cases were considered as under treatment failure mainly due to recurrence of parasitemia on day 7 (four patients, day 14 (six patients, and day 21 (one patient. The age of all cases of treatment failures was found to be less than 20 years. The load of parasitemia of patients with treatment failure on day of admission (4709.4/μl was higher than day of recurrence (372.37/μl. Parasite reduction ratio (PRR of treatment failure cases was 12.6/μl. Conclusion This report revealed the rise in treatment failure (13% [95% CI = 0.074 - 0.217] as compared to earlier reports from Ethiopia. It signals the spreading of chloroquine resistant P. vivax (CRPv strains to malaria endemic areas of Ethiopia. It is recommended that all concerned bodies should act aggressively before further expansion of the current drug resistant malaria.

  10. TAPIR--Finnish national geochemical baseline database.

    Science.gov (United States)

    Jarva, Jaana; Tarvainen, Timo; Reinikainen, Jussi; Eklund, Mikael

    2010-09-15

    In Finland, a Government Decree on the Assessment of Soil Contamination and Remediation Needs has generated a need for reliable and readily accessible data on geochemical baseline concentrations in Finnish soils. According to the Decree, baseline concentrations, referring both to the natural geological background concentrations and the diffuse anthropogenic input of substances, shall be taken into account in the soil contamination assessment process. This baseline information is provided in a national geochemical baseline database, TAPIR, that is publicly available via the Internet. Geochemical provinces with elevated baseline concentrations were delineated to provide regional geochemical baseline values. The nationwide geochemical datasets were used to divide Finland into geochemical provinces. Several metals (Co, Cr, Cu, Ni, V, and Zn) showed anomalous concentrations in seven regions that were defined as metal provinces. Arsenic did not follow a similar distribution to any other elements, and four arsenic provinces were separately determined. Nationwide geochemical datasets were not available for some other important elements such as Cd and Pb. Although these elements are included in the TAPIR system, their distribution does not necessarily follow the ones pre-defined for metal and arsenic provinces. Regional geochemical baseline values, presented as upper limit of geochemical variation within the region, can be used as trigger values to assess potential soil contamination. Baseline values have also been used to determine upper and lower guideline values that must be taken into account as a tool in basic risk assessment. If regional geochemical baseline values are available, the national guideline values prescribed in the Decree based on ecological risks can be modified accordingly. The national geochemical baseline database provides scientifically sound, easily accessible and generally accepted information on the baseline values, and it can be used in various

  11. BMC{trademark}: Baseline report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-31

    Barrier Membrane Containment (BMC){trademark} is a high-density polyethylene membrane (HOPE) groundwater barrier and pass-through system, with applications ranging from plume control and containment to groundwater manipulation coupled with in-site treatment. BMC{trademark} system can function as a permeable or impermeable reaction wall, a cut-off wall, interceptor trenches, a barrier with collection and/or monitoring system and a pass-through in a funnel and gate configuration. BMC{trademark} can be inspected with a down-hole video camera, producing a permanent VHS format tape, insuring the integrity of the wall and the interlocking joints. The joints are sealed with a ``U``-packing elastomeric gasket to prevent the flow of fluids or gases.

  12. Influence of Baseline Characteristics, Operative Conduct and Postoperative Course on 30-day Outcomes of Coronary Artery Bypass Grafting among Patients with Left Ventricular Dysfunction: Results from the Surgical Treatment for Ischemic Heart Failure (STICH) Trial

    Science.gov (United States)

    Wrobel, Krzysztof; Stevens, Susanna R.; Jones, Robert H.; Selzman, Craig H.; Lamy, Andre; Beaver, Thomas M.; Djokovic, Ljubomir T.; Wang, Nan; Velazquez, Eric J.; Sopko, George; Kron, Irving L.; DiMaio, J. Michael; Michler, Robert E.; Lee, Kerry L.; Yii, Michael; Leng, Chua Yeow; Zembala, Marian; Rouleau, Jean L.; Daly, Richard C.; Al-Khalidi, Hussein R.

    2015-01-01

    Background Patients with severe left ventricular (LV) dysfunction, ischemic heart failure and coronary artery disease (CAD) suitable for coronary artery bypass grafting (CABG) are at higher risk for surgical morbidity and mortality. Paradoxically, those patients with the most severe coronary artery disease and ventricular dysfunction who derive the greatest clinical benefit from CABG are also at the greatest operative risk, which makes decision-making regarding whether to proceed to surgery difficult in such patients. To better inform such decision-making, we analyzed the STICH CABG population for detailed information on perioperative risk and outcomes. Methods and Results In both STICH trials (hypotheses), 2136 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and coronary artery disease were allocated to medical therapy, CABG plus medical therapy or CABG with surgical ventricular reconstruction (SVR). Relationships of baseline characteristics and operative conduct with morbidity and mortality at 30 days were evaluated. There were a total of 1460 patients who received surgery, and 346 of them (roughly, one-quarter) of these high-risk patients developed a severe complication within 30 days. Worsening renal insufficiency, cardiac arrest with cardiopulmonary resuscitation, and ventricular arrhythmias were the most frequent complications and those most commonly associated with death. Mortality at 30 days was 5.1% and was generally preceded by a serious complication (65 of 74 deaths). LV size, renal dysfunction, advanced age, and atrial fibrillation/flutter were significant preoperative predictors of mortality within 30 days. Cardiopulmonary bypass time was the only independent surgical variable predictive of 30-day mortality. Conclusions CABG can be performed with relatively low 30-day mortality in patients with LV dysfunction. Serious postoperative complications occurred in nearly 1 in 4 patients and were associated with mortality. Clinical Trial

  13. Arc melter demonstration baseline test results

    Energy Technology Data Exchange (ETDEWEB)

    Soelberg, N.R.; Chambers, A.G.; Anderson, G.L.; Oden, L.L.; O`Connor, W.K.; Turner, P.C.

    1994-07-01

    This report describes the test results and evaluation for the Phase 1 (baseline) arc melter vitrification test series conducted for the Buried Waste Integrated Demonstration program (BWID). Phase 1 tests were conducted on surrogate mixtures of as-incinerated wastes and soil. Some buried wastes, soils, and stored wastes at the INEL and other DOE sites, are contaminated with transuranic (TRU) radionuclides and hazardous organics and metals. The high temperature environment in an electric arc furnace may be used to process these wastes to produce materials suitable for final disposal. An electric arc furnace system can treat heterogeneous wastes and contaminated soils by (a) dissolving and retaining TRU elements and selected toxic metals as oxides in the slag phase, (b) destroying organic materials by dissociation, pyrolyzation, and combustion, and (c) capturing separated volatilized metals in the offgas system for further treatment. Structural metals in the waste may be melted and tapped separately for recycle or disposal, or these metals may be oxidized and dissolved into the slag. The molten slag, after cooling, will provide a glass/ceramic final waste form that is homogeneous, highly nonleachable, and extremely durable. These features make this waste form suitable for immobilization of TRU radionuclides and toxic metals for geologic timeframes. Further, the volume of contaminated wastes and soils will be substantially reduced in the process.

  14. Life Support Baseline Values and Assumptions Document

    Science.gov (United States)

    Anderson, Molly S.; Ewert, Michael K.; Keener, John F.; Wagner, Sandra A.

    2015-01-01

    The Baseline Values and Assumptions Document (BVAD) provides analysts, modelers, and other life support researchers with a common set of values and assumptions which can be used as a baseline in their studies. This baseline, in turn, provides a common point of origin from which many studies in the community may depart, making research results easier to compare and providing researchers with reasonable values to assume for areas outside their experience. With the ability to accurately compare different technologies' performance for the same function, managers will be able to make better decisions regarding technology development.

  15. NRAO Very Long Baseline Array (VLBA)

    Data.gov (United States)

    Federal Laboratory Consortium — The Very Long Baseline Array (VLBA) comprises ten radio telescopes spanning 5,351 miles. It's the world's largest, sharpest, dedicated telescope array. With an eye...

  16. SSA FITARA Common Baseline Implementation Plan

    Data.gov (United States)

    Social Security Administration — This document describes the agency's plan to implement the Federal Information Technology Acquisition Reform Act (FITARA) Common Baseline per OMB memorandum M-15-14.

  17. Breton Island, Louisiana Baseline (Geographic, NAD83)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Breton Island, Louisiana Baseline (Geographic, NAD83) consists of vector line data that were input into the Digital Shoreline Analysis System (DSAS) version 4.0,...

  18. Determinants of delay in malaria treatment-seeking behaviour for under-five children in south-west Ethiopia: a case control study

    Directory of Open Access Journals (Sweden)

    Deribew Amare

    2010-11-01

    Full Text Available Abstract Background Prompt diagnosis and timely treatment of malaria within 24 hours after onset of first symptoms can reduce illness progression to severe stages and therefore, decrease mortality. The reason why mothers/caretakers delay in malaria diagnosis and treatment for under-five children is not well studied in Ethiopia. The objective of this study was to assess determinants of malaria treatment delay in under-five children in three districts of south-west Ethiopia. Methods A case control study was conducted from March 15 to April 20, 2010. Cases were under-five children who had clinical malaria and sought treatment after 24 hours of developing sign and symptom, and controls were under-five children who had clinical malaria and sought treatment within 24 hours of developing sign and symptom of malaria. Data were collected by trained enumerators using structured questionnaire. Data were entered in to Epi Info version 6.04 and analyzed using SPSS version 16.0. To identify determinants, multiple logistic regression was done. Results A total of 155 mothers of cases and 155 mothers of controls were interviewed. Mothers of children who were in a monogamous marriage (OR = 3.41, 95% CI: 1.39, 8.34, who complained about the side effects of anti-malarial drugs (OR = 4.96, 95% CI: 1.21, 20.36, who had no history of child death (OR = 3.50, 95% CI: 1.82, 6.42 and who complained about the higher cost of transportation to reach the health institutions (OR = 2.01, 95% CI: 1.17, 3.45 were more likely to be late for the treatment of malaria in under-five children. Conclusion Effective malaria control programmes should address reducing delayed presentation of children for treatment. Efforts to reduce delay should address transport cost, decentralization of services and increasing awareness of the community on early diagnosis and treatment.

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

    Directory of Open Access Journals (Sweden)

    Barnes Karen I

    2010-12-01

    Full Text Available Abstract Background 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. Methods The pharmacology module of WWARN has established a quality assurance/quality control (QA/QC programme consisting of two separate components: 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. 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. Conclusion 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. By utilizing the same source of standards for all laboratories, it is possible to minimize bias arising from poor

  20. Salton Sea sampling program: baseline studies

    Energy Technology Data Exchange (ETDEWEB)

    Tullis, R.E.; Carter, J.L.; Langlois, G.W.

    1981-04-13

    Baseline data are provided on three species of fish from the Salton Sea, California. The fishes considered were the orange mouth corvina (Cynoscion xanthulus), gulf croaker (Bairdiella icistius) and sargo (Anisotremus davidsonii). Morphometric and meristic data are presented as a baseline to aid in the evaluation of any physiological stress the fish may experience as a result of geothermal development. Analyses were made on muscle, liver, and bone of the fishes sampled to provide baseline data on elemental tissue burdens. The elements measured were: As, Br, Ca, Cu, Fe, Ga, K, Mn, Mi, Pb, Rb, Se, Sr, Zn, and Zr. These data are important if an environmentally sound progression of geothermal power production is to occur at the Salton Sea.

  1. Baseline methodologies for clean development mechanism projects

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M.K. (ed.); Shrestha, R.M.; Sharma, S.; Timilsina, G.R.; Kumar, S.

    2005-11-15

    The Kyoto Protocol and the Clean Development Mechanism (CDM) came into force on 16th February 2005 with its ratification by Russia. The increasing momentum of this process is reflected in more than 100 projects having been submitted to the CDM Executive Board (CDM-EB) for approval of the baselines and monitoring methodologies, which is the first step in developing and implementing CDM projects. A CDM project should result in a net decrease of GHG emissions below any level that would have resulted from other activities implemented in the absence of that CDM project. The 'baseline' defines the GHG emissions of activities that would have been implemented in the absence of a CDM project. The baseline methodology is the process/algorithm for establishing that baseline. The baseline, along with the baseline methodology, are thus the most critical element of any CDM project towards meeting the important criteria of CDM, which are that a CDM should result in 'real, measurable, and long term benefits related to the mitigation of climate change'. This guidebook is produced within the frame work of the United Nations Environment Programme (UNEP) facilitated 'Capacity Development for the Clean Development Mechanism (CD4CDM)' Project. This document is published as part of the projects effort to develop guidebooks that cover important issues such as project finance, sustainability impacts, legal framework and institutional framework. These materials are aimed to help stakeholders better understand the CDM and are believed to eventually contribute to maximize the effect of the CDM in achieving the ultimate goal of UNFCCC and its Kyoto Protocol. This Guidebook should be read in conjunction with the information provided in the two other guidebooks entitled, 'Clean Development Mechanism: Introduction to the CDM' and 'CDM Information and Guidebook' developed under the CD4CDM project. (BA)

  2. Long-baseline Neutrino Oscillation at DUNE

    Science.gov (United States)

    Worcester, Elizabeth; DUNE Collaboration Collaboration

    2017-01-01

    The Deep Underground Neutrino Experiment (DUNE) is a long-baseline neutrino oscillation experiment with primary physics goals of determining the neutrino mass hierarchy and measuring δc P with sufficient sensitivity to discover CP violation in neutrino oscillation. CP violation sensitivity in DUNE requires careful understanding of systematic uncertainty, with contributions expected from uncertainties in the neutrino flux, neutrino interactions, and detector effects. In this presentation, we will describe the expected sensitivity of DUNE to long-baseline neutrino oscillation parameters, how various aspects of the experimental design contribute to that sensitivity, and the planned strategy for constraining systematic uncertainty in these measurements.

  3. Neutrino Interactions and Long-Baseline Experiments

    CERN Document Server

    Mosel, Ulrich

    2016-01-01

    The extraction of neutrino mixing parameters and the CP-violating phase requires knowledge of the neutrino energy. This energy must be reconstructed from the final state of a neutrino-nucleus reaction since all long-baseline experiments use nuclear targets. This reconstruction requires detailed knowledge of the neutrino reactions with bound nucleons and of the final state interactions of hadrons with the nuclear environment. Quantum-kinetic transport theory can be used to build an event generator for this reconstruction that takes basic nuclear properties, such as binding, into account. Some examples are discussed that show the effects of nuclear interactions on observables in long-baseline experiments

  4. 40 CFR 80.90 - Conventional gasoline baseline emissions determination.

    Science.gov (United States)

    2010-07-01

    ... using the facility's oxygenated individual baseline fuel parameter values for summer and winter (per... using the oxygenated individual baseline fuel parameter values for summer and winter (per § 80.91... baseline NOX emissions shall be determined using the baseline individual baseline fuel parameter values...

  5. Solid Waste Program technical baseline description

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, A.B.

    1994-07-01

    The system engineering approach has been taken to describe the technical baseline under which the Solid Waste Program is currently operating. The document contains a mission analysis, function analysis, system definition, documentation requirements, facility and project bases, and uncertainties facing the program.

  6. How Valid Are the Portland Baseline Essays?

    Science.gov (United States)

    Martel, Erich

    1991-01-01

    Portland, Oregon's "African-American Baseline Essays," widely used in creating multicultural curricula, inaccurately depicts ancient Egyptians as black people and Olmec civilization as derived from African influences. The authors advance racial theories long abandoned by mainline Africa scholars, attribute mystical powers to pyramids,…

  7. Waste management project technical baseline description

    Energy Technology Data Exchange (ETDEWEB)

    Sederburg, J.P.

    1997-08-13

    A systems engineering approach has been taken to describe the technical baseline under which the Waste Management Project is currently operating. The document contains a mission analysis, function analysis, requirement analysis, interface definitions, alternative analysis, system definition, documentation requirements, implementation definitions, and discussion of uncertainties facing the Project.

  8. Guidance on Port Biological Baseline Surveys (PBBS)

    Digital Repository Service at National Institute of Oceanography (India)

    Awad, A.; Haag, F.; Anil, A.C.; Abdulla, A.

    This publication has been prepared by GBP, IOI, CSIR-NIO and IUCN in order to serve as guidance to those who are planning to carry out a port biological baseline survey, in particular in the context of Ballast Water Management. It has been drafted...

  9. Rationing in the presence of baselines

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter

    2013-01-01

    We analyze a general model of rationing in which agents have baselines, in addition to claims against the (insufficient) endowment of the good to be allocated. Many real-life problems fit this general model (e.g., bankruptcy with prioritized claims, resource allocation in the public health care...

  10. Application of mobile-technology for disease and treatment monitoring of malaria in the "Better Border Healthcare Programme"

    Directory of Open Access Journals (Sweden)

    Meankaew Pongthep

    2010-08-01

    Full Text Available Abstract Background The main objective of this study was to assess the effectiveness of integrating the use of cell-phones into a routine malaria prevention and control programme, to improve the management of malaria cases among an under-served population in a border area. The module for disease and treatment monitoring of malaria (DTMM consisted of case investigation and case follow-up for treatment compliance and patients' symptoms. Methods The module combining web-based and mobile technologies was developed as a proof of concept, in an attempt to replace the existing manual, paper-based activities that malaria staff used in treating and caring for malaria patients in the villages for which they were responsible. After a patient was detected and registered onto the system, case-investigation and treatment details were recorded into the malaria database. A follow-up schedule was generated, and the patient's status was updated when the malaria staff conducted their routine home visits, using mobile phones loaded with the follow-up application module. The module also generated text and graph messages for a summary of malaria cases and basic statistics, and automatically fed to predetermined malaria personnel for situation analysis. Following standard public-health practices, access to the patient database was strictly limited to authorized personnel in charge of patient case management. Results The DTMM module was developed and implemented at the trial site in late November 2008, and was fully functioning in 2009. The system captured 534 malaria patients in 2009. Compared to paper-based data in 2004-2008, the mobile-phone-based case follow-up rates by malaria staff improved significantly. The follow-up rates for both Thai and migrant patients were about 94-99% on Day 7 (Plasmodium falciparum and Day 14 (Plasmodium vivax and maintained at 84-93% on Day 90. Adherence to anti-malarial drug therapy, based on self-reporting, showed high completion

  11. Efficacy and tolerability of a new formulation of artesunate-mefloquine for the treatment of uncomplicated malaria in adult in Senegal: open randomized trial

    Directory of Open Access Journals (Sweden)

    CK Tine Roger

    2012-12-01

    Full Text Available Abstract Background Prompt treatment of malaria attacks with arteminisin-based combination therapy (ACT is an essential tool for malaria control. A new co-blister tablet of artesunate-mefloquine (AM with 25 mg/kg mefloquine has been developed for the management of uncomplicated malaria attacks. This non-inferiority randomized trial, was conducted to evaluate the efficacy and safety of the new formulation of AM in comparison to artemether-lumefantrine (AL for the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in Senegal. Methods The study was carried out from September to December 2010 in two health centres in Senegal. The study end points included (i PCR corrected adequate clinical and parasitological response (ACPR at day 28, (ii ACPR at days 42 and 63, (iii parasites and fever clearance time, (iv incidence of adverse events and patients biological profile at day 7 using the WHO 2003 protocol for anti-malarial drug evaluation. Results Overall, 310 patients were randomized to receive either AM (n = 157 or AL (n = 153. PCR corrected ACPR at day 28 was at 95.5% in the AM arm while that in the AL arm was at 96.7% (p = 0.83. Therapeutic efficacy was at 98.5% in the AM arm versus 98.2% in the AL group at day 42 (p = 1. At day 63, ACPR in the AM and AL arms was at 98.2% and 97.7%, respectively (p = 0.32. The two treatments were well tolerated with similar biological profile at day 7. However, dizziness was more frequent in the AM arm. Conclusion Artesunate-mefloquine (25 mg/Kg mefloquine is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients.

  12. CASA Uno GPS orbit and baseline experiments

    Science.gov (United States)

    Schutz, B. E.; Ho, C. S.; Abusali, P. A. M.; Tapley, B. D.

    1990-01-01

    CASA Uno data from sites distributed in longitude from Australia to Europe have been used to determine orbits of the GPS satellites. The characteristics of the orbits determined from double difference phase have been evaluated through comparisons of two-week solutions with one-week solutions and by comparisons of predicted and estimated orbits. Evidence of unmodeled effects is demonstrated, particularly associated with the orbit planes that experience solar eclipse. The orbit accuracy has been assessed through the repeatability of unconstrained estimated baseline vectors ranging from 245 km to 5400 km. Both the baseline repeatability and the comparison with independent space geodetic methods give results at the level of 1-2 parts in 100,000,000. In addition, the Mojave/Owens Valley (245 km) and Kokee Park/Ft. Davis (5409 km) estimates agree with VLBI and SLR to better than 1 part in 100,000,000.

  13. Dissipative Effect in Long Baseline Neutrino Experiments

    CERN Document Server

    Oliveira, Roberto L N

    2016-01-01

    The propagation of neutrinos in long baselines experiments may be influenced by dissipation effects. Using Lindblad Master Equation we evolve neutrinos taking into account these dissipative effects. The MSW and the dissipative effects may change the probabilities behavior. In this work, we show and explain how the behavior of the probabilities can change due to the decoherence and relaxation effects acting individually with the MSW effect. A new exotic peak appears in this case and we show the difference between the decoherence and relaxation effects in the appearance of this peak. We also adapt the usual approximate expression for survival and appearance probabilities with all possible decoherence effects. We suppose the baseline of DUNE and show how each decoherence parameters change the probabilities analyzing the possible modification using numeric and analytic approach.

  14. Joint Multi-baseline SAR Interferometry

    Directory of Open Access Journals (Sweden)

    S. Tebaldini

    2005-12-01

    Full Text Available We propose a technique to provide interferometry by combining multiple images of the same area. This technique differs from the multi-baseline approach in literature as (a it exploits all the images simultaneously, (b it performs a spectral shift preprocessing to remove most of the decorrelation, and (c it exploits distributed targets. The technique is mainly intended for DEM generation at centimetric accuracy, as well as for differential interferometry. The problem is framed in the contest of single-input multiple-output (SIMO channel estimation via the cross-relations (CR technique and the resulting algorithm provides significant improvements with respect to conventional approaches based either on independent analysis of single interferograms or multi-baselines phase analysis of single pixels of current literature, for those targets that are correlated in all the images, like for long-term coherent areas, or for acquisitions taken with a short revisit time (as those gathered with future satellite constellations.

  15. The Gambia Impact Evaluation Baseline Report

    OpenAIRE

    2015-01-01

    The Government of The Gambia is implementing the Maternal and Child Nutrition and Health Results Project (MCNHRP) to increase the utilization of community nutrition and primary maternal and child health services. In collaboration with the Government, the World Bank is conducting an impact evaluation (IE) to assess the impact of the project on key aspects of maternal and child nutrition and health. The baseline survey for the MCNHRP IE took place between November 2014 and February 2015. It c...

  16. Systematic errors in long baseline oscillation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Deborah A.; /Fermilab

    2006-02-01

    This article gives a brief overview of long baseline neutrino experiments and their goals, and then describes the different kinds of systematic errors that are encountered in these experiments. Particular attention is paid to the uncertainties that come about because of imperfect knowledge of neutrino cross sections and more generally how neutrinos interact in nuclei. Near detectors are planned for most of these experiments, and the extent to which certain uncertainties can be reduced by the presence of near detectors is also discussed.

  17. Efficient Wide Baseline Structure from Motion

    Science.gov (United States)

    Michelini, Mario; Mayer, Helmut

    2016-06-01

    This paper presents a Structure from Motion approach for complex unorganized image sets. To achieve high accuracy and robustness, image triplets are employed and (an approximate) camera calibration is assumed to be known. The focus lies on a complete linking of images even in case of large image distortions, e.g., caused by wide baselines, as well as weak baselines. A method for embedding image descriptors into Hamming space is proposed for fast image similarity ranking. The later is employed to limit the number of pairs to be matched by a wide baseline method. An iterative graph-based approach is proposed formulating image linking as the search for a terminal Steiner minimum tree in a line graph. Finally, additional links are determined and employed to improve the accuracy of the pose estimation. By this means, loops in long image sequences are implicitly closed. The potential of the proposed approach is demonstrated by results for several complex image sets also in comparison with VisualSFM.

  18. Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model

    Directory of Open Access Journals (Sweden)

    Souraud Jean-Baptiste

    2012-01-01

    Full Text Available Abstract Background One of the major complications of Plasmodium falciparum infection is cerebral malaria (CM, which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ and quinine. Methods The efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental Plasmodium berghei ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining. Results AVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown. Conclusions The combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of P. berghei ANKA-infected mice.

  19. Baseline Response Levels Are a Nuisance in Infant Contingency Learning

    Science.gov (United States)

    Millar, W. S.; Weir, Catherine

    2015-01-01

    The impact of differences in level of baseline responding on contingency learning in the first year was examined by considering the response acquisition of infants classified into baseline response quartiles. Whereas the three lower baseline groups showed the predicted increment in responding to a contingency, the highest baseline responders did…

  20. The value of baseline CT head scans in the assessment of shunt complications in hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Cantrell, P. (Alder Hey Children' s Hospital, Liverpool (United Kingdom)); Fraser, F. (Alder Hey Children' s Hospital, Liverpool (United Kingdom)); Pilling, D. (Alder Hey Children' s Hospital, Liverpool (United Kingdom)); Carty, H. (Alder Hey Children' s Hospital, Liverpool (United Kingdom))

    1993-10-01

    The purpose of this study was to determine the value of a baseline CT head scan in the assessment of patients who subsequently presented with symptoms which may have been due to shunt complications (such as blockage or infection). In all these patients the shunt had been inserted in the treatment of hydrocephalus. We conclude that the presence of a baseline scan does not add to the interpretation of CT scans done when the patient presents with symptoms of possible shunt malfunction. (orig.)

  1. Barriers to prompt and effective malaria treatment among the poorest population in Kenya

    Directory of Open Access Journals (Sweden)

    Okungu Vincent

    2010-05-01

    Full Text Available Abstract Background Prompt access to effective malaria treatment is central to the success of malaria control worldwide, but few fevers are treated with effective anti-malarials within 24 hours of symptoms onset. The last two decades saw an upsurge of initiatives to improve access to effective malaria treatment in many parts of sub-Saharan Africa. Evidence suggests that the poorest populations remain least likely to seek prompt and effective treatment, but the factors that prevent them from accessing interventions are not well understood. With plans under way to subsidize ACT heavily in Kenya and other parts of Africa, there is urgent need to identify policy actions to promote access among the poor. This paper explores access barriers to effective malaria treatment among the poorest population in four malaria endemic districts in Kenya. Methods The study was conducted in the poorest areas of four malaria endemic districts in Kenya. Multiple data collection methods were applied including: a cross-sectional survey (n = 708 households; 24 focus group discussions; semi-structured interviews with health workers (n = 34; and patient exit interviews (n = 359. Results Multiple factors related to affordability, acceptability and availability interact to influence access to prompt and effective treatment. Regarding affordability, about 40 percent of individuals who self-treated using shop-bought drugs and 42 percent who visited a formal health facility reported not having enough money to pay for treatment, and having to adopt coping strategies including borrowing money and getting treatment on credit in order to access care. Other factors influencing affordability were seasonality of illness and income sources, transport costs, and unofficial payments. Regarding acceptability, the major interrelated factors identified were provider patient relationship, patient expectations, beliefs on illness causation, perceived effectiveness of treatment, distrust in

  2. Very Long Baseline Interferometry with the SKA

    CERN Document Server

    Paragi, Zsolt; Reynolds, Cormac; Rioja, Maria; Deller, Adam; Zhang, Bo; Gurvits, Leonid; Bietenholz, Michael; Szomoru, Arpad; Bignall, Hayley; Boven, Paul; Charlot, Patrick; Dodson, Richard; Frey, Sandor; Garrett, Michael; Imai, Hiroshi; Lobanov, Andrei; Reid, Mark; Ros, Eduardo; van Langevelde, Huib; Zensus, J Anton; Zheng, Xing Wu; Alberdi, Antxon; Agudo, Ivan; An, Tao; Argo, Megan; Beswick, Rob; Biggs, Andy D; Brunthaler, Andreas; Campbell, Robert M; Cimo, Giuseppe; Colomer, Francisco; Corbel, Stephane; Conway, John; Cseh, David; Deane, Roger; Falcke, Heino; Gabanyi, Krisztina; Gawronski, Marcin; Gaylard, Michael; Giovannini, Gabriele; Giroletti, Marcello; Goddi, Ciriaco; Goedhart, Sharmila; Gomez, Jose L; Gunn, Alastair; Jung, Taehyun; Kharb, Preeti; Klockner, Hans-Rainer; Kording, Elmar; Kovalev, Yurii Yu; Kunert-Bajraszewska, Magdalena; Lindqvist, Michael; Lister, Matt; Mantovani, Franco; Marti-Vidal, Ivan; Mezcua, Mar; McKean, John; Middelberg, Enno; Miller-Jones, James; Moldon, Javier; Muxlow, Tom; O'Brien, Tim; Pérez-Torres, Miguel; Pogrebenko, Sergei; Quick, Jonathan; Rushton, Anthony P; Schilizzi, Richard; Smirnov, Oleg; Sohn, Bong Won; Surcis, Gabriele; Taylor, Greg; Tingay, Steven; Tudose, Valeriu; van der Horst, Alexander; van Leeuwen, Joeri; Venturi, Tiziana; Vermeulen, Rene; Vlemmings, Wouter; de Witt, Aletha; Wucknitz, Olaf; Yang, Jun

    2014-01-01

    Adding VLBI capability to the SKA arrays will greatly broaden the science of the SKA, and is feasible within the current specifications. SKA-VLBI can be initially implemented by providing phased-array outputs for SKA1-MID and SKA1-SUR and using these extremely sensitive stations with other radio telescopes, and in SKA2 by realising a distributed configuration providing baselines up to thousands of km, merging it with existing VLBI networks. The motivation for and the possible realization of SKA-VLBI is described in this paper.

  3. Optimization of the CLIC Baseline Collimation System

    Energy Technology Data Exchange (ETDEWEB)

    Resta-Lopez, Javier; /Oxford U., JAI; Angal-Kalinin, Deepa; /Daresbury; Fernandez-Hernando, Juan; /Daresbury; Jackson, Frank; /Daresbury; Dalena, Barbara; /CERN; Schulte, Daniel; /CERN; Tomas, Rogelio; /CERN; Seryi, Andrei; /SLAC

    2012-07-06

    Important efforts have recently been dedicated to the improvement of the design of the baseline collimation system of the Compact Linear Collider (CLIC). Different aspects of the design have been optimized: the transverse collimation depths have been recalculated in order to reduce the collimator wakefield effects while maintaining a good efficiency in cleaning the undesired beam halo; the geometric design of the spoilers have also been reviewed to minimize wakefields; in addition, the optics design have been polished to improve the collimation efficiency. This paper describes the current status of the CLIC collimation system after this optimization.

  4. SRP baseline hydrogeologic investigation, Phase 2

    Energy Technology Data Exchange (ETDEWEB)

    Bledsoe, H.W.

    1987-11-01

    As discussed in the program plan for the Savannah River Plant (SRP) Baseline Hydrogeologic Investigation, this program has been implemented for the purpose of updating and improving the current state of knowledge and understanding of the hydrogeologic systems underlying the Savannah River Plant (SRP). The objective of the program is to install a series of observation well clusters (wells installed in each major water bearing formation at the same site) at key locations across the plant site in order to: (1) provide detailed information on the lithology, stratigraphy, and groundwater hydrology, (2) provide observation wells to monitor the groundwater quality, head relationships, gradients, and flow paths.

  5. SRP Baseline Hydrogeologic Investigation, Phase 3

    Energy Technology Data Exchange (ETDEWEB)

    Bledsoe, H.W.

    1988-08-01

    The SRP Baseline Hydrogeologic Investigation was implemented for the purpose of updating and improving the knowledge and understanding of the hydrogeologic systems underlying the SRP site. Phase III, which is discussed in this report, includes the drilling of 7 deep coreholes (sites P-24 through P-30) and the installation of 53 observation wells ranging in depth from approximately 50 ft to more than 970 ft below the ground surface. In addition to the collection of geologic cores for lithologic and stratigraphic study, samples were also collected for the determination of physical characteristics of the sediments and for the identification of microorganisms.

  6. SRP baseline hydrogeologic investigation: Aquifer characterization

    Energy Technology Data Exchange (ETDEWEB)

    Strom, R.N.; Kaback, D.S.

    1992-03-31

    An investigation of the mineralogy and chemistry of the principal hydrogeologic units and the geochemistry of the water in the principal aquifers at Savannah River Site (SRS) was undertaken as part of the Baseline Hydrogeologic Investigation. This investigation was conducted to provide background data for future site studies and reports and to provide a site-wide interpretation of the geology and geochemistry of the Coastal Plain Hydrostratigraphic province. Ground water samples were analyzed for major cations and anions, minor and trace elements, gross alpha and beta, tritium, stable isotopes of hydrogen, oxygen, and carbon, and carbon-14. Sediments from the well borings were analyzed for mineralogy and major and minor elements.

  7. Baseline and benchmark model development for hotels

    Science.gov (United States)

    Hooks, Edward T., Jr.

    The hotel industry currently faces rising energy costs and requires the tools to maximize energy efficiency. In order to achieve this goal a clear definition of the current methods used to measure and monitor energy consumption is made. Uncovering the limitations to the most common practiced analysis strategies and presenting methods that can potentially overcome those limitations is the main purpose. Techniques presented can be used for measurement and verification of energy efficiency plans and retrofits. Also, modern energy modeling tool are introduced to demonstrate how they can be utilized for benchmarking and baseline models. This will provide the ability to obtain energy saving recommendations and parametric analysis to explore energy savings potential. These same energy models can be used in design decisions for new construction. An energy model is created of a resort style hotel that over one million square feet and has over one thousand rooms. A simulation and detailed analysis is performed on a hotel room. The planning process for creating the model and acquiring data from the hotel room to calibrate and verify the simulation will be explained. An explanation as to how this type of modeling can potentially be beneficial for future baseline and benchmarking strategies for the hotel industry. Ultimately the conclusion will address some common obstacles the hotel industry has in reaching their full potential of energy efficiency and how these techniques can best serve them.

  8. Vegetation baseline report : Connacher great divide project

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-08-01

    This baseline report supported an application by Connacher Oil and Gas Ltd. to the Alberta Energy and Utilities Board (EUB) and Alberta Environment (AENV) for the Great Divide Steam Assisted Gravity Drainage (SAGD) Project. The goal of the report was to document the distribution and occurrence of ecosite phases and wetland classes in the project footprint as well as to document the distribution of rare plants; rare plant communities: and intrusive species and old growth communities, including species of management concern. A methodology of the baseline report was presented, including details of mapping and field surveys. Six vegetation types in addition to the disturbed land unit were identified in the project footprint and associated buffer. It was noted that all vegetation types are common for the boreal forest natural regions. Several species of management concern were identified during the spring rare plant survey, including rare bryophytes and non-native or invasive species. Mitigation was identified through a slight shift of the footprint, transplant of appropriate bryophyte species and implementation of a weed management plan. It was noted that results of future surveys for rare plants will be submitted upon completion. It was concluded that the effects of the project on existing vegetation is expected to be low because of the small footprint, prior disturbance history, available mitigation measures and conservation and reclamation planning. 27 refs., 5 tabs., 4 figs.

  9. Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine

    Directory of Open Access Journals (Sweden)

    Adjei George O

    2012-12-01

    Full Text Available Abstract Background Several anti-malarial drugs are associated with adverse cardiovascular effects. These effects may be exacerbated when different anti-malarials are used in combination. There has been no report yet on the potential cardiac effects of the combination artesunate-amodiaquine. Methods Electrocardiographic (ECG intervals in Ghanaian children with uncomplicated malaria treated with artesunate-amodiaquine (n=47, were compared with that of children treated with artemether-lumefantrine (n=30. The ECG measurements were repeated one, two, three, seven and 28 days after treatment. The ECG intervals of artesunate-amodiaquine treated subjects were correlated with plasma concentrations of desethylamodiaquine (DEAQ, the main metabolite of amodiaquine. Results The mean ECG intervals were similar in both groups before treatment. After treatment (day 3, ECG intervals changed significantly from baseline in all subjects, but there were no differences between the two treatment groups. A significantly higher proportion of children treated with artesunate-amodiaquine developed sinus bradycardia compared with artemether-lumefantrine treated subjects (7/47 vs 0/30; χ2 p=0.03. Subjects who developed bradycardia were significantly older, and had higher DEAQ concentrations than those who did not develop bradycardia. The proportion of subjects with QTc interval prolongations did not differ significantly between the groups, and no relationship between prolonged QTc intervals and DEAQ levels were observed. No clinically significant rhythm disturbances were observed in any of the subjects. Conclusion Artesunate-amodiaquine treatment resulted in a higher incidence of sinus bradycardia than artemether-lumefantrine treatment in children with uncomplicated malaria, but no clinically significant rhythm disturbances were induced by combining artesunate with amodiaquine. These findings, although reassuring, may imply that non-amodiaquine based artemisinin

  10. Tightly coupled long baseline/ultra-short baseline integrated navigation system

    Science.gov (United States)

    Batista, Pedro; Silvestre, Carlos; Oliveira, Paulo

    2016-06-01

    This paper proposes a novel integrated navigation filter based on a combined long baseline/ultra short baseline acoustic positioning system with application to underwater vehicles. With a tightly coupled structure, the position, linear velocity, attitude, and rate gyro bias are estimated, considering the full nonlinear system dynamics without resorting to any algebraic inversion or linearisation techniques. The resulting solution ensures convergence of the estimation error to zero for all initial conditions, exponentially fast. Finally, it is shown, under simulation environment, that the filter achieves very good performance in the presence of sensor noise.

  11. [The noise filtering and baseline correction for harmonic spectrum based on wavelet transform].

    Science.gov (United States)

    Guo, Yuan; Zhao, Xue-Hong; Zhang, Rui; Hu, Ya-Jun; Wang, Yan

    2013-08-01

    The problem of noise and baseline drift is a hot topic in infrared spectral harmonic detection system. This paper presents a new algorithm based on wavelet transform Mallet decomposition to solve the problem of eliminating a variety of complex noise and baseline drift in the harmonic detection. In the algorithm, the appropriate wavelet function and decomposition level were selected to decomposed the noise, baseline drift and useful signal in the harmonic curve into different frequency bands. the bands' information was analysed and a detecting band was set, then the information in useful frequency was reserved by zeroing method of treatment and the coefficient of the threshold. We can just use once transform and reconstruction to remove interference noise and baseline from double-harmonic signal by applying the wavelet transform technique to the harmonic detection spectrum pretreatment. Experiments show that the wavelet transform method can be used to different harmonic detection systems and has universal applicability.

  12. Pentek concrete scabbling system: Baseline report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-31

    The Pentek scabbling technology was tested at Florida International University (FIU) and is being evaluated as a baseline technology. This report evaluates it for safety and health issues. It is a commercially available technology and has been used for various projects at locations throughout the country. The Pentek concrete scabbling system consisted of the MOOSE{reg_sign}, SQUIRREL{reg_sign}-I, and SQUIRREL{reg_sign}-III scabblers. The scabblers are designed to scarify concrete floors and slabs using cross-section, tungsten carbide tipped bits. The bits are designed to remove concrete in 318 inch increments. The bits are either 9-tooth or demolition type. The scabblers are used with a vacuum system designed to collect and filter the concrete dust and contamination that is removed from the surface. The safety and health evaluation during the human factors assessment focused on two main areas: noise and dust.

  13. The WITCH Model. Structure, Baseline, Solutions.

    Energy Technology Data Exchange (ETDEWEB)

    Bosetti, V.; Massetti, E.; Tavoni, M.

    2007-07-01

    WITCH - World Induced Technical Change Hybrid - is a regionally disaggregated hard link hybrid global model with a neoclassical optimal growth structure (top down) and an energy input detail (bottom up). The model endogenously accounts for technological change, both through learning curves affecting prices of new vintages of capital and through R and D investments. The model features the main economic and environmental policies in each world region as the outcome of a dynamic game. WITCH belongs to the class of Integrated Assessment Models as it possesses a climate module that feeds climate changes back into the economy. In this paper we provide a thorough discussion of the model structure and baseline projections. We report detailed information on the evolution of energy demand, technology and CO2 emissions. Finally, we explicitly quantifiy the role of free riding in determining the emissions scenarios. (auth)

  14. Octant degeneracy, CPV phase at Long Baseline $\

    CERN Document Server

    Bora, Kalpana; Dutta, Debajyoti

    2015-01-01

    In a recent work by two of us, we have studied, how CP violation discovery potential can be improved at long baseline neutrino experiments (LBNE/DUNE), by combining with its ND (near detector) and reactor experiments. In this work, we discuss how this study can be further analysed to resolve entanglement of the quadrant of CPV phase and Octant of atmospheric mixing angle {\\theta}23, at LBNEs. The study is done for both NH (Normal hierarchy) and IH (Inverted hierarchy). We further show how leptogenesis can enhance this effect of resolving this entanglement. A detailed analytic and numerical study of baryogenesis through leptogenesis is performed in this framework in a model independent way. We then compare our result of the baryon to photon ratio with the the current observational data of the baryon asymmetry.

  15. Intensity interferometry: Optical imaging with kilometer baselines

    CERN Document Server

    Dravins, Dainis

    2016-01-01

    Optical imaging with microarcsecond resolution will reveal details across and outside stellar surfaces but requires kilometer-scale interferometers, challenging to realize either on the ground or in space. Intensity interferometry, electronically connecting independent telescopes, has a noise budget that relates to the electronic time resolution, circumventing issues of atmospheric turbulence. Extents up to a few km are becoming realistic with arrays of optical air Cherenkov telescopes (primarily erected for gamma-ray studies), enabling an optical equivalent of radio interferometer arrays. Pioneered by Hanbury Brown and Twiss, digital versions of the technique have now been demonstrated, reconstructing diffraction-limited images from laboratory measurements over hundreds of optical baselines. This review outlines the method from its beginnings, describes current experiments, and sketches prospects for future observations.

  16. The OPERA long baseline neutrino oscillation experiment

    Science.gov (United States)

    Wilquet, G.

    2008-05-01

    OPERA is a long baseline neutrino oscillation experiment designed to observe the appearance of vτ in a pure vμ beam in the parameter space indicated by the atmospheric neutrinos oscillation signal. The detector is situated in the underground LNGS laboratory under 3 800 water meter equivalent at a distance of 730 km from CERN where the CNGS neutrino beam to which it is exposed originates. It consists of two identical 0.68 kilotons lead/nuclear emulsion targets, each instrumented with a tracking device and complemented by a muon spectrometer. The concept and the status of the detector are described and the first results obtained with cosmic rays and during two weeks of beam commissioning in 2006 are reported.

  17. In-Space Manufacturing Baseline Property Development

    Science.gov (United States)

    Stockman, Tom; Schneider, Judith; Prater, Tracie; Bean, Quincy; Werkheiser, Nicki

    2016-01-01

    The In-Space Manufacturing (ISM) project at NASA Marshall Space Flight Center currently operates a 3D FDM (fused deposition modeling) printer onboard the International Space Station. In order to enable utilization of this capability by designer, the project needs to establish characteristic material properties for materials produced using the process. This is difficult for additive manufacturing since standards and specifications do not yet exist for these technologies. Due to availability of crew time, there are limitations to the sample size which in turn limits the application of the traditional design allowables approaches to develop a materials property database for designers. In this study, various approaches to development of material databases were evaluated for use by designers of space systems who wish to leverage in-space manufacturing capabilities. This study focuses on alternative statistical techniques for baseline property development to support in-space manufacturing.

  18. Steganography Based on Baseline Sequential JPEG Compression

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Information hiding in Joint Photographic Experts Group (JPEG) compressed images are investigated in this paper. Quantization is the source of information loss in JPEG compression process. Therefore, information hidden in images is probably destroyed by JPEG compression. This paper presents an algorithm to reliably embed information into the JPEG bit streams in the process of JPEG encoding. Information extraction is performed in the process of JPEG decoding. The basic idea of our algorithm is to modify the quantized direct current (DC) coefficients and non-zero alternating current (AC) coefficients to represent one bit information (0 or 1). Experimental results on gray images using baseline sequential JPEG encoding show that the cover images (images without secret information) and the stego-images (images with secret information) are perceptually indiscernible.

  19. Radio sources - Very, Very Long Baseline Interferometry

    Science.gov (United States)

    Roberts, D. H.

    1983-03-01

    With resolution of a thousandth of an arcsecond, the radio technique of Very Long Baseline Interferometry (VLBI) provides astronomers with their highest-resolution view of the universe. Data taken with widely-separated antennas are combined, with the help of atomic clocks, to form a Michelson interferometer whose size may be as great as the earth's diameter. Extraordinary phenomena, from the birth of stars as signaled by the brilliant flashes of powerful interstellar masers to the 'faster-than-light' expansion of the cores of distant quasars, are being explored with this technique. However, earth-bound VLBI suffers from several restrictions due to the location of the component antennas at fixed places on the earth's surface. The use of one or more antennas in space in concert with ground-based equipment will greatly expand the technical and scientific capabilities of VLBI, leading to a more complete and even higher resolution view of cosmic phenomena.

  20. Biological baseline data Youngs Bay, Oregon, 1974

    Energy Technology Data Exchange (ETDEWEB)

    McMechan, K.J. (ed.); Higley, D.L.; Holton, R.L.

    1975-04-01

    This report presents biological baseline information gathered during the research project, Physical, Chemical and Biological Studies on Youngs Bay.'' Youngs Bay is a shallow embayment located on the south shore of the Columbia River, near Astoria, Oregon. Research on Youngs Bay was motivated by the proposed construction by Alumax Pacific Aluminum Corporation of an aluminum reduction plant at Warrenton, Oregon. The research was designed to provide biological baseline information on Youngs Bay in anticipation of potential harmful effects from plant effluents. The information collected concerns the kinds of animals found in the Youngs Bay area, and their distribution and seasonal patterns of abundance. In addition, information was collected on the feeding habits of selected fish species, and on the life history and behavioral characteristics of the most abundant benthic amphipod, Corophium salmonis. Sampling was conducted at approximately three-week intervals, using commonly accepted methods of animal collection. Relatively few stations were sampled for fish, because of the need to standardize conditions of capture. Data on fish capture are reported in terms of catch-per-unit effort by a particular sampling gear at a specific station. Methods used in sampling invertebrates were generally more quantitative, and allowed sampling at a greater variety of places, as well as a valid basis for the computation of densities. Checklists of invertebrate species and fish species were developed from these samples, and are referred to throughout the report. The invertebrate checklist is more specific taxonomically than are tables reporting invertebrate densities. This is because the methods employed in identification were more precise than those used in counts. 9 refs., 27 figs., 25 tabs.

  1. 贵州省社区女性人群高血压基线调查与社区综合防治效果评价%Baseline investigation of female hypertension and effect evaluation of community comprehensive prevention and treatment in Guizhou

    Institute of Scientific and Technical Information of China (English)

    潘仰中; 蔡运昌; 郑流波; 柳桂娥; 张彪; 谢春凤; 刘宏珍; 邓小林; 夏旻

    2005-01-01

    administrative areas.SETTING: Guizhou Institute of Cardiovascular Disease, Renmin Hospital of Yunyan District in Guiyang, Guizhou Clinical Examination Center.PARTICIPANTS: Since 1996, a series of comprehensive prevention and treatment had been carried in the communities for cardiac cerebral vascular disease in Guizhou, involved 13 administrative areas and 112 villagecitizen groups, in which, 26 604 people were employed, living in the regions between town and country. Social natural condition and life behavior of majority citizen reflected the common state of people in town and country. Totally 3 934 people aged over 15 years were investigated in the communities, and were all in the known of investigation. The samples without complete data were excluded.METHODS: ① Base-line investigation was carried on for the groups over 15 years old according to the requirement for administrative region designed by Institute of Preventive Medicine of China Academy of Sciences from April 1st 2001 to May 15th . ② Health education and health promotion activity were carried on for the included groups. ③ Survey after intervention was given for females according to the survey items designed by Institute of Preventive Medicine of China Academy of Sciences from July 2002to June 2003. ④ Normal body-mass index (BMI) was 18.5-23.9 kg/m2,overweight was indicated if BMI was 24-27.9 kg/m2 and obesity was diagnosed if BMI ≥28 kg/m2. ⑤ Analysis was applied on comparison of BMI,waist to hip ratio (WHR), average blood pressure, the rates of incidence,awareness and treatment of hypertension and rate of high-salty and lipid diet. ⑥ t test was adopted for comparison of means between two samples and x2 test was used for rate comparison.MAIN OUTCOME MEASURES: ① Comparison of the rates of incidence, awareness, treatment and control of hypertension for females of different ages in community base-line investigation in Guizhou. ② Comparison of BMI, WHR and BP of females of various ages in baseline

  2. Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Rodolfo Thomé

    Full Text Available BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg cells and suppressive Dendritic Cells (DCs, to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ, an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE, an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55 peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of

  3. Digital Offshore Cadastre (DOC) - Pacific83 - Baseline Tangent Lines

    Data.gov (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This data set contains baseline tangent lines and bay closing lines in ESRI Arc/Info export and Arc/View shape file formats for the BOEM Pacific Region. Baseline...

  4. The effect of short-baseline neutrino oscillations on LBNE

    Energy Technology Data Exchange (ETDEWEB)

    Louis, William C. [Physics Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

    2015-10-15

    Short-baseline neutrino oscillations can have a relatively big effect on long-baseline oscillations, due to the cross terms that arise from multiple mass scales. The existing short-baseline anomalies suggest that short-baseline oscillations can affect the ν{sub μ} → ν{sub e} appearance probabilities by up to 20-40%, depending on the values of the CP-violating parameters.

  5. The effect of short-baseline neutrino oscillations on LBNE

    Science.gov (United States)

    Louis, William C.

    2015-10-01

    Short-baseline neutrino oscillations can have a relatively big effect on long-baseline oscillations, due to the cross terms that arise from multiple mass scales. The existing short-baseline anomalies suggest that short-baseline oscillations can affect the νμ → νe appearance probabilities by up to 20-40%, depending on the values of the CP-violating parameters.

  6. Utilities and offsites design baseline. Outside Battery Limits Facility 6000 tpd SRC-I Demonstration Plant. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    None

    1984-05-25

    As part of the overall Solvent Refined Coal (SRC-1) project baseline being prepared by International Coal Refining Company (ICRC), the RUST Engineering Company is providing necessary input for the Outside Battery Limits (OSBL) Facilities. The project baseline is comprised of: design baseline - technical definition of work; schedule baseline - detailed and management level 1 schedules; and cost baseline - estimates and cost/manpower plan. The design baseline (technical definition) for the OSBL Facilities has been completed and is presented in Volumes I, II, III, IV, V and VI. The OSBL technical definition is based on, and compatible with, the ICRC defined statement of work, design basis memorandum, master project procedures, process and mechanical design criteria, and baseline guidance documents. The design basis memorandum is included in Paragraph 1.3 of Volume I. The baseline design data is presented in 6 volumes. Volume I contains the introduction section and utility systems data through steam and feedwater. Volume II continues with utility systems data through fuel system, and contains the interconnecting systems and utility system integration information. Volume III contains the offsites data through water and waste treatment. Volume IV continues with offsites data, including site development and buildings, and contains raw materials and product handling and storage information. Volume V contains wastewater treatment and solid wastes landfill systems developed by Catalytic, Inc. to supplement the information contained in Volume III. Volume VI contains proprietary information of Resources Conservation Company related to the evaporator/crystallizer system of the wastewater treatment area.

  7. Self-reported fever, treatment actions and malaria infection prevalence in the northern states of Sudan

    Directory of Open Access Journals (Sweden)

    Abdelgadir Tareg M

    2011-05-01

    Full Text Available Abstract Background The epidemiology of fevers and their management in areas of low malaria transmission in Africa is not well understood. The characteristics of fever, its treatment and association with infection prevalence from a national household sample survey in the northern states of Sudan, an area that represents historically low parasite prevalence, are examined in this study. Methods In October-November 2009, a cluster sample cross-sectional household malaria indicator survey was undertaken in the 15 northern states of the Sudan. Data on household assets and individual level information on age, sex, whether the individual had a fever in the last 14 days and on the day of survey, actions taken to treat the fever including diagnostic services and drugs used and their sources were collected. Consenting household members were asked to provide a finger-prick blood sample and examined for malaria parasitaemia using a rapid diagnostic test (RDT. All proportions and odds ratios were weighted and adjusted for clustering. Results Of 26,471 respondents 19% (n = 5,299 reported a history of fever within the last two weeks prior to the survey and 8% had fever on the day of the survey. Only 39% (n = 2,035 of individuals with fever in last two weeks took any action, of which 43% (n = 875 were treated with anti-malarials. About 44% (n = 382 of malaria treatments were done using the nationally recommended first-line therapy artesunate+sulphadoxine-pryrimethamine (AS+SP and 13% (n = 122 with non-recommended chloroquine or SP. Importantly 33.9% (n = 296 of all malaria treatments included artemether monotherapy, which is internationally banned for the treatment of uncomplicated malaria. About 53% of fevers had some form of parasitological diagnosis before treatment. On the day of survey, 21,988 individuals provided a finger-prick blood sample and only 1.8% were found positive for Plasmodium falciparum. Infection prevalence was higher among individuals who

  8. 10 CFR 850.20 - Baseline beryllium inventory.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Baseline beryllium inventory. 850.20 Section 850.20 Energy... Baseline beryllium inventory. (a) The responsible employer must develop a baseline inventory of the... inventory, the responsible employer must: (1) Review current and historical records; (2) Interview...

  9. Resetting predator baselines in coral reef ecosystems

    Science.gov (United States)

    Bradley, Darcy; Conklin, Eric; Papastamatiou, Yannis P.; McCauley, Douglas J.; Pollock, Kydd; Pollock, Amanda; Kendall, Bruce E.; Gaines, Steven D.; Caselle, Jennifer E.

    2017-01-01

    What did coral reef ecosystems look like before human impacts became pervasive? Early efforts to reconstruct baselines resulted in the controversial suggestion that pristine coral reefs have inverted trophic pyramids, with disproportionally large top predator biomass. The validity of the coral reef inverted trophic pyramid has been questioned, but until now, was not resolved empirically. We use data from an eight-year tag-recapture program with spatially explicit, capture-recapture models to re-examine the population size and density of a key top predator at Palmyra atoll, the same location that inspired the idea of inverted trophic biomass pyramids in coral reef ecosystems. Given that animal movement is suspected to have significantly biased early biomass estimates of highly mobile top predators, we focused our reassessment on the most mobile and most abundant predator at Palmyra, the grey reef shark (Carcharhinus amblyrhynchos). We estimated a density of 21.3 (95% CI 17.8, 24.7) grey reef sharks/km2, which is an order of magnitude lower than the estimates that suggested an inverted trophic pyramid. Our results indicate that the trophic structure of an unexploited reef fish community is not inverted, and that even healthy top predator populations may be considerably smaller, and more precarious, than previously thought. PMID:28220895

  10. Gated integrator with signal baseline subtraction

    Science.gov (United States)

    Wang, Xucheng

    1996-01-01

    An ultrafast, high precision gated integrator includes an opamp having differential inputs. A signal to be integrated is applied to one of the differential inputs through a first input network, and a signal indicative of the DC offset component of the signal to be integrated is applied to the other of the differential inputs through a second input network. A pair of electronic switches in the first and second input networks define an integrating period when they are closed. The first and second input networks are substantially symmetrically constructed of matched components so that error components introduced by the electronic switches appear symmetrically in both input circuits and, hence, are nullified by the common mode rejection of the integrating opamp. The signal indicative of the DC offset component is provided by a sample and hold circuit actuated as the integrating period begins. The symmetrical configuration of the integrating circuit improves accuracy and speed by balancing out common mode errors, by permitting the use of high speed switching elements and high speed opamps and by permitting the use of a small integrating time constant. The sample and hold circuit substantially eliminates the error caused by the input signal baseline offset during a single integrating window.

  11. Gated integrator with signal baseline subtraction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.

    1996-12-17

    An ultrafast, high precision gated integrator includes an opamp having differential inputs. A signal to be integrated is applied to one of the differential inputs through a first input network, and a signal indicative of the DC offset component of the signal to be integrated is applied to the other of the differential inputs through a second input network. A pair of electronic switches in the first and second input networks define an integrating period when they are closed. The first and second input networks are substantially symmetrically constructed of matched components so that error components introduced by the electronic switches appear symmetrically in both input circuits and, hence, are nullified by the common mode rejection of the integrating opamp. The signal indicative of the DC offset component is provided by a sample and hold circuit actuated as the integrating period begins. The symmetrical configuration of the integrating circuit improves accuracy and speed by balancing out common mode errors, by permitting the use of high speed switching elements and high speed opamps and by permitting the use of a small integrating time constant. The sample and hold circuit substantially eliminates the error caused by the input signal baseline offset during a single integrating window. 5 figs.

  12. The LOFAR long baseline snapshot calibrator survey

    CERN Document Server

    Moldón, J; Wucknitz, O; Jackson, N; Drabent, A; Carozzi, T; Conway, J; Kapińska, A D; McKean, P; Morabito, L; Varenius, E; Zarka, P; Anderson, J; Asgekar, A; Avruch, I M; Bell, M E; Bentum, M J; Bernardi, G; Best, P; Bîrzan, L; Bregman, J; Breitling, F; Broderick, J W; Brüggen, M; Butcher, H R; Carbone, D; Ciardi, B; de Gasperin, F; de Geus, E; Duscha, S; Eislöffel, J; Engels, D; Falcke, H; Fallows, R A; Fender, R; Ferrari, C; Frieswijk, W; Garrett, M A; Grießmeier, J; Gunst, A W; Hamaker, J P; Hassall, T E; Heald, G; Hoeft, M; Juette, E; Karastergiou, A; Kondratiev, V I; Kramer, M; Kuniyoshi, M; Kuper, G; Maat, P; Mann, G; Markoff, S; McFadden, R; McKay-Bukowski, D; Morganti, R; Munk, H; Norden, M J; Offringa, A R; Orru, E; Paas, H; Pandey-Pommier, M; Pizzo, R; Polatidis, A G; Reich, W; Röttgering, H; Rowlinson, A; Scaife, A M M; Schwarz, D; Sluman, J; Smirnov, O; Stappers, B W; Steinmetz, M; Tagger, M; Tang, Y; Tasse, C; Thoudam, S; Toribio, M C; Vermeulen, R; Vocks, C; van Weeren, R J; White, S; Wise, M W; Yatawatta, S; Zensus, A

    2014-01-01

    Aims. An efficient means of locating calibrator sources for International LOFAR is developed and used to determine the average density of usable calibrator sources on the sky for subarcsecond observations at 140 MHz. Methods. We used the multi-beaming capability of LOFAR to conduct a fast and computationally inexpensive survey with the full International LOFAR array. Sources were pre-selected on the basis of 325 MHz arcminute-scale flux density using existing catalogues. By observing 30 different sources in each of the 12 sets of pointings per hour, we were able to inspect 630 sources in two hours to determine if they possess a sufficiently bright compact component to be usable as LOFAR delay calibrators. Results. Over 40% of the observed sources are detected on multiple baselines between international stations and 86 are classified as satisfactory calibrators. We show that a flat low-frequency spectrum (from 74 to 325 MHz) is the best predictor of compactness at 140 MHz. We extrapolate from our sample to sho...

  13. Lorentz symmetry and Very Long Baseline Interferometry

    CERN Document Server

    Poncin-Lafitte, C Le; lambert, S

    2016-01-01

    Lorentz symmetry violations can be described by an effective field theory framework that contains both General Relativity and the Standard Model of particle physics called the Standard-Model extension (SME). Recently, post-fit analysis of Gravity Probe B and binary pulsars lead to an upper limit at the $10^{-4}$ level on the time-time coefficient $\\bar s^{TT}$ of the pure-gravity sector of the minimal SME. In this work, we derive the observable of Very Long Baseline Interferometry (VLBI) in SME and then we implement it into a real data analysis code of geodetic VLBI observations. Analyzing all available observations recorded since 1979, we compare estimates of $\\bar s^{TT}$ and errors obtained with various analysis schemes, including global estimations over several time spans and with various Sun elongation cut-off angles, and with analysis of radio source coordinate time series. We obtain a constraint on $\\bar s^{TT}=(-5\\pm 8)\\times 10^{-5}$, directly fitted to the observations and improving by a factor 5 pr...

  14. The LBNO long-baseline oscillation sensitivities with two conventional neutrino beams at different baselines

    CERN Document Server

    Agarwalla, S.K.; Aittola, M.; Alekou, A.; Andrieu, B.; Antoniou, F.; Asfandiyarov, R.; Autiero, D.; Besida, O.; Balik, A.; Ballett, P.; Bandac, I.; Banerjee, D.; Bartmann, W.; Bay, F.; Biskup, B.; Blebea-Apostu, A.M.; Blondel, A.; Bogomilov, M.; Bolognesi, S.; Borriello, E.; Brancus, I.; Bravar, A.; Buizza-Avanzini, M.; Caiulo, D.; Calin, M.; Calviani, M.; Campanelli, M.; Cantini, C.; Cata-Danil, G.; Chakraborty, S.; Charitonidis, N.; Chaussard, L.; Chesneanu, D.; Chipesiu, F.; Crivelli, P.; Dawson, J.; De Bonis, I.; Declais, Y.; del Amo Sanchez, P.; Delbart, A.; Di Luise, S.; Duchesneau, D.; Dumarchez, J.; Efthymiopoulos, I.; Eliseev, A.; Emery, S.; Enqvist, T.; Enqvist, K.; Epprecht, L.; Erykalov, A.N.; Esanu, T.; Franco, D.; Friend, M.; Galymov, V.; Gavrilov, G.; Gendotti, A.; Giganti, C.; Gilardoni, S.; Goddard, B.; Gomoiu, C.M.; Gornushkin, Y.A.; Gorodetzky, P.; Haesler, A.; Hasegawa, T.; Horikawa, S.; Huitu, K.; Izmaylov, A.; Jipa, A.; Kainulainen, K.; Karadzhov, Y.; Khabibullin, M.; Khotjantsev, A.; Kopylov, A.N.; Korzenev, A.; Kosyanenko, S.; Kryn, D.; Kudenko, Y.; Kuusiniemi, P.; Lazanu, I.; Lazaridis, C.; Levy, J.M.; Loo, K.; Maalampi, J.; Margineanu, R.M.; Marteau, J.; Martin-Mari, C.; Matveev, V.; Mazzucato, E.; Mefodiev, A.; Mineev, O.; Mirizzi, A.; Mitrica, B.; Murphy, S.; Nakadaira, T.; Narita, S.; Nesterenko, D.A.; Nguyen, K.; Nikolics, K.; Noah, E.; Novikov, Yu.; Oprima, A.; Osborne, J.; Ovsyannikova, T.; Papaphilippou, Y.; Pascoli, S.; Patzak, T.; Pectu, M.; Pennacchio, E.; Periale, L.; Pessard, H.; Popov, B.; Ravonel, M.; Rayner, M.; Resnati, F.; Ristea, O.; Robert, A.; Rubbia, A.; Rummukainen, K.; Saftoiu, A.; Sakashita, K.; Sanchez-Galan, F.; Sarkamo, J.; Saviano, N.; Scantamburlo, E.; Sergiampietri, F.; Sgalaberna, D.; Shaposhnikova, E.; Slupecki, M.; Smargianaki, D.; Stanca, D.; Steerenberg, R.; Sterian, A.R.; Sterian, P.; Stoica, S.; Strabel, C.; Suhonen, J.; Suvorov, V.; Toma, G.; Tonazzo, A.; Trzaska, W.H.; Tsenov, R.; Tuominen, K.; Valram, M.; Vankova-Kirilova, G.; Vannucci, F.; Vasseur, G.; Velotti, F.; Velten, P.; Venturi, V.; Viant, T.; Vihonen, S.; Vincke, H.; Vorobyev, A.; Weber, A.; Wu, S.; Yershov, N.; Zambelli, L.; Zito, M.

    2014-01-01

    The proposed Long Baseline Neutrino Observatory (LBNO) initially consists of $\\sim 20$ kton liquid double phase TPC complemented by a magnetised iron calorimeter, to be installed at the Pyh\\"asalmi mine, at a distance of 2300 km from CERN. The conventional neutrino beam is produced by 400 GeV protons accelerated at the SPS accelerator delivering 700 kW of power. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the $L/E$ behaviour, and distinguishing effects arising from $\\delta_{CP}$ and matter. In this paper we show how this comprehensive physics case can be further enhanced and complemented if a neutrino beam produced at the Protvino IHEP accelerator complex, at a distance of 1160 km, and with modest power of 450 kW is aimed towards the same far detectors. We show that the coupling of two independent sub-MW conventional neutrino and antineutrino beams at different baselines from CERN and Protvino will allow to measure ...

  15. Baseline glucocorticoids are drivers of body mass gain in a diving seabird

    Science.gov (United States)

    Hennin, Holly; Berlin, Alicia; Love, Oliver P.

    2016-01-01

    Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic–pituitary–adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

  16. Using Syllable-Timed Speech to Treat Preschool Children Who Stutter: A Multiple Baseline Experiment

    Science.gov (United States)

    Trajkovski, Natasha; Andrews, Cheryl; Onslow, Mark; Packman, Ann; O'Brian, Sue; Menzies, Ross

    2009-01-01

    This report presents the results of an experimental investigation of the effects of a syllable-timed speech treatment on three stuttering preschool children. Syllable-timed speech involves speaking with minimal differentiation in linguistic stress across syllables. Three children were studied in a multiple baseline across participants design, with…

  17. Efficacy and safety of a fixed dose artesunate-sulphamethoxypyrazine-pyrimethamine compared to artemether-lumefantrine for the treatment of uncomplicated falciparum malaria across Africa: a randomized multi-centre trial

    Directory of Open Access Journals (Sweden)

    Djimdé Abdoulaye

    2009-04-01

    Full Text Available Abstract Background The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance. Methods Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP three-day (once daily for 3 days regimen (N = 476 or AS-SMP 24-hour (0 h, 12 h, 24 h regimen (N = 458 or artemether-lumefantrine (AL, the regular 6 doses regimen (N = 450. The primary objective was to demonstrate non-inferiority (using a margin of -6% of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate. Results The PCR corrected 28-day cure rate on the intention to treat (ITT analysis population were: 96.0%(457/476 in the AS-SMP three-day group, 93.7%(429/458 in the AS-SMP 24-hour group and 92.0%(414/450 in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437 in the AS-SMP three-day group, 99.5%(416/419 in the AS-SMP 24-hour group and 99.7(391/394% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea which were slightly higher in the AS-SMP 24-hour group. Conclusion AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated. Trial registration NCT00484900 http://www.clinicaltrials.gov.

  18. Baseline Substance Use Interferes with Maintenance of HIV Medication Adherence Skills.

    Science.gov (United States)

    Dale, Sannisha K; Traeger, Lara; O'Cleirigh, Conall; Bedoya, C Andres; Pinkston, Megan; Wilner, Julianne G; Stein, Michael; Safren, Steven A

    2016-05-01

    Cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV improves both adherence and depression outcomes relative to enhanced treatment as usual (ETAU). However, in persons with injection drug use (PWIDU) histories, adherence gains seen during treatment have not been maintained postintervention. Therefore, we examined whether heroin or cocaine use at study entry moderated acquisition or maintenance of adherence gains after CBT-AD. HIV-positive adults in treatment for opioid dependence (n = 89) were randomly assigned to CBT-AD or ETAU and completed 3-, 6-, and 12-month assessments. Participants were majority male (61%), white (48%), and heterosexual (79%). Hierarchical linear modeling was used to evaluate whether heroin or cocaine use at baseline interacted with intervention assignment to predict change in adherence during active treatment and follow-up. CBT-AD-related improvement in adherence during the active intervention period did not vary by baseline substance use. However, cocaine use (but not heroin use) at baseline interacted with intervention assignment to predict a significant decline in follow-up adherence (cocaine use × group condition coefficient = -0.77, t = -2.44, p = 0.02) such that by 12 months, adherence among CBT participants was significantly lower among those who used cocaine (45.0%) compared to those who did not (72.3%; t = 2.50, p = 0.018). HIV-positive PWIDU who use heroin or cocaine at baseline can benefit from the CBT-AD intervention to improve adherence to antiretroviral therapy; therefore, providers should not withhold an active psychosocial treatment for HIV-positive PWIDU who are using. Cocaine use at baseline may limit the degree to which gains are maintained postintervention, and therefore, booster sessions may be needed.

  19. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents.

    Science.gov (United States)

    De Monte, Celeste; Bizzarri, Bruna; Gidaro, Maria Concetta; Carradori, Simone; Mollica, Adriano; Luisi, Grazia; Granese, Arianna; Alcaro, Stefano; Costa, Giosuè; Basilico, Nicoletta; Parapini, Silvia; Scaltrito, Maria Maddalena; Masia, Carla; Sisto, Francesca

    2015-12-01

    Crocus sativus L. is known in herbal medicine for the various pharmacological effects of its components, but no data are found in literature about its biological properties toward Helicobacter pylori, Plasmodium spp. and Leishmania spp. In this work, the potential anti-bacterial and anti-parasitic effects of crocin and safranal, two important bioactive components in C. sativus, were explored, and also some semi-synthetic derivatives of safranal were tested in order to establish which modifications in the chemical structure could improve the biological activity. According to our promising results, we virtually screened our compounds by means of molecular modeling studies against the main H. pylori enzymes in order to unravel their putative mechanism of action.

  20. PfMDR2 and PfMDR5 are dispensable for Plasmodium falciparum asexual parasite multiplication but change in vitro susceptibility to anti-malarial drugs

    NARCIS (Netherlands)

    Velden, M. van der; Rijpma, S.R.; Russel, F.G.M.; Sauerwein, R.W.; Koenderink, J.B.

    2015-01-01

    BACKGROUND: Membrane-associated ATP binding cassette (ABC) transport proteins hydrolyze ATP in order to translocate a broad spectrum of substrates, from single ions to macromolecules across membranes. In humans, members from this transport family have been linked to drug resistance phenotypes, e.g.,

  1. Two New Plant-Like Pathways Link Hemoglobin Degradation to Lipid Biogenesis in Falciparum Malaria: Novel Targets for Anti-Malarial Chemotherapy

    Science.gov (United States)

    2005-03-01

    important parasitic disease, is caused by intraerythrocytic protozoan parasites of the genus Plasmodium. Plasmodium falciparum is responsible for the most...been proposed to be the primaryM caused by intraerythrocytic protozoan parasites of the route for synthesis of PtdCho in Plasmodium (16, 17); however

  2. Efficacy comparison between anti-malarial drugs in Africans presenting with mild malaria in the Central Republic of Africa: a preliminary study

    Directory of Open Access Journals (Sweden)

    Nambei W.S.

    2005-03-01

    Full Text Available Drug resistance to Plasmodium falciparum contributes to major health problems in central Africa and, as a consequence, poverty. We have analyzed the efficacy of three currently available antimalarial drugs to treat symptomatic, uncomplicated P. falciparum malaria in semiimmune adults living in Bangui, Central Republic of Africa. 210 consecutive individuals were enrolled in the survey, of which 45 were excluded. Those having received dihydroartemisin proved significantly less parasitemic than those having received quinine per os or sulfadoxin-pyrimethamin (χ2 = 16.93 ; p < 0.05, and 75 % recovered in two days compared to 57 and 44 %, respectively. The 25 % who did not recover benefited from a second cure with dihydroartemisin, which proved 100 % efficient. The most accurate protocol remains to be established by analyzing clinical and parasitological data and taking into account the economics of the country.

  3. The acceptability of mass administrations of anti-malarial drugs as part of targeted malaria elimination in villages along the Thai–Myanmar border

    Directory of Open Access Journals (Sweden)

    Ladda Kajeechiwa

    2016-09-01

    Full Text Available Abstract Background A targeted malaria elimination project, including mass drug administrations (MDA of dihydroartemisinin/piperaquine plus a single low dose primaquine is underway in villages along the Thailand Myanmar border. The intervention has multiple components but the success of the project will depend on the participation of the entire communities. Quantitative surveys were conducted to study reasons for participation or non-participation in the campaign with the aim to identify factors associated with the acceptance and participation in the mass drug administrations. Methods The household heads in four study villages in which MDAs had taken place previously were interviewed between January 2014 and July 2015. Results 174/378 respondents (46 % completed three rounds of three drug doses each, 313/378 (83 % took at least three consecutive doses and 56/378 (15 % did not participate at all in the MDA. The respondents from the two villages (KNH and TPN were much more likely to participate in the MDA than respondents from the other two villages (HKT and TOT. The more compliant villages KNH and TPN had both an appearance of cohesive communities with similar demographic and ethnic backgrounds. By contrast the villages with low participation were unique. One village was fragmented following years of armed conflict and many respondents gave little inclination to cooperate with outsiders. The other village with low MDA coverage was characterised by a high percentage of short-term residents with little interest in community interventions. A universal reason for non-participation in the MDA applicable to all villages was an inadequate understanding of the intervention. Conclusions It is unlikely that community engagement can unite fragmented communities in participating in an intervention, which benefits the community. Understanding the purpose and the reasons underlying the intervention is an important pre-condition for participation. In the absence of direct benefits and a complete understanding of the indirect benefits trust in the investigators is critical for participation.

  4. Identification of Selective Inhibitors of the Plasmodium falciparum Hexose Transporter PfHT by Screening Focused Libraries of Anti-Malarial Compounds.

    Directory of Open Access Journals (Sweden)

    Diana Ortiz

    Full Text Available Development of resistance against current antimalarial drugs necessitates the search for novel drugs that interact with different targets and have distinct mechanisms of action. Malaria parasites depend upon high levels of glucose uptake followed by inefficient metabolic utilization via the glycolytic pathway, and the Plasmodium falciparum hexose transporter PfHT, which mediates uptake of glucose, has thus been recognized as a promising drug target. This transporter is highly divergent from mammalian hexose transporters, and it appears to be a permease that is essential for parasite viability in intra-erythrocytic, mosquito, and liver stages of the parasite life cycle. An assay was developed that is appropriate for high throughput screening against PfHT based upon heterologous expression of PfHT in Leishmania mexicana parasites that are null mutants for their endogenous hexose transporters. Screening of two focused libraries of antimalarial compounds identified two such compounds that are high potency selective inhibitors of PfHT compared to human GLUT1. Additionally, 7 other compounds were identified that are lower potency and lower specificity PfHT inhibitors but might nonetheless serve as starting points for identification of analogs with more selective properties. These results further support the potential of PfHT as a novel drug target.

  5. BMC{trademark}: Baseline report; Greenbook (chapter)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-31

    Barrier Membrane Containment (BMC){trademark} is a high-density polyethylene membrane (HDPE) groundwater barrier and pass-through system, with applications ranging from plume control and containment to groundwater manipulation coupled with in-site treatment. BMC{trademark} system can function as a permeable or impermeable reaction wall, a cut-off wall, interceptor trenches, a barrier with collection and/or monitoring system, and a pass-through in a funnel and gate configuration. BMC{trademark} can be inspected with a down-hole video camera, producing a permanent VHS format tape, insuring the integrity of the wall and the interlocking joints.

  6. Conditional analysis of mixed Poisson processes with baseline counts: implications for trial design and analysis.

    Science.gov (United States)

    Cook, Richard J; Wei, Wei

    2003-07-01

    The design of clinical trials is typically based on marginal comparisons of a primary response under two or more treatments. The considerable gains in efficiency afforded by models conditional on one or more baseline responses has been extensively studied for Gaussian models. The purpose of this article is to present methods for the design and analysis of clinical trials in which the response is a count or a point process, and a corresponding baseline count is available prior to randomization. The methods are based on a conditional negative binomial model for the response given the baseline count and can be used to examine the effect of introducing selection criteria on power and sample size requirements. We show that designs based on this approach are more efficient than those proposed by McMahon et al. (1994).

  7. Effect of Enamel Caries Lesion Baseline Severity on Fluoride Dose-Response

    Directory of Open Access Journals (Sweden)

    Frank Lippert

    2017-01-01

    Full Text Available This study aimed to investigate the effect of enamel caries lesion baseline severity on fluoride dose-response under pH cycling conditions. Early caries lesions were created in human enamel specimens at four different severities (8, 16, 24, and 36 h. Lesions were allocated to treatment groups (0, 83, and 367 ppm fluoride as sodium fluoride based on Vickers surface microhardness (VHN and pH cycled for 5 d. The cycling model comprised 3 × 1 min fluoride treatments sandwiched between 2 × 60 min demineralization challenges with specimens stored in artificial saliva in between. VHN was measured again and changes versus lesion baseline were calculated (ΔVHN. Data were analyzed using two-way ANOVA (p<0.05. Increased demineralization times led to increased surface softening. The lesion severity×fluoride concentration interaction was significant (p<0.001. Fluoride dose-response was observed in all groups. Lesions initially demineralized for 16 and 8 h showed similar overall rehardening (ΔVHN and more than 24 and 36 h lesions, which were similar. The 8 h lesions showed the greatest fluoride response differential (367 versus 0 ppm F which diminished with increasing lesion baseline severity. The extent of rehardening as a result of the 0 ppm F treatment increased with increasing lesion baseline severity, whereas it decreased for the fluoride treatments. In conclusion, lesion baseline severity impacts the extent of the fluoride dose-response.

  8. Using Baseline Studies in the Investigation of Test Impact

    Science.gov (United States)

    Wall, Dianne; Horak, Tania

    2007-01-01

    The purpose of this article is to discuss the role of "baseline studies" in investigations of test impact and to illustrate the type of thinking underlying the design and implementation of such studies by reference to a recent study relating to a high-stakes test of English language proficiency. Baseline studies are used to describe an educational…

  9. Digital Offshore Cadastre (DOC) - Pacific83 - Baseline Points

    Data.gov (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This data set contains baseline points in ESRI Arc/Info export and Arc/View shape file formats for the BOEM Pacific Region. Baseline points are used by the BOEM to...

  10. Searching for neutrino oscillation parameters in long baseline experiments

    CERN Document Server

    Vihonen, Sampsa

    2016-01-01

    Developing neutrino astronomy requires a good understanding of the neutrino oscillations mechanism. The European strategy for neutrino oscillation physics sets a high priority on future long baseline neutrino experiments with the aim to measure the intrinsic parameters that govern the neutrino oscillations. In this work we take a look at the next generation of long baseline experiments and discuss their prospects in future research.

  11. The 2014 ALMA Long Baseline Campaign : An Overview

    NARCIS (Netherlands)

    ALMA Partnership, [Unknown; Fomalont, E. B.; Vlahakis, C.; Corder, S.; Remijan, A.; Barkats, D.; Lucas, R.; Hunter, T. R.; Brogan, C. L.; Asaki, Y.; Matsushita, S.; Dent, W. R. F.; Hills, R. E.; Phillips, N.; Richards, A. M. S.; Cox, P.; Amestica, R.; Broguiere, D.; Cotton, W.; Hales, A. S.; Hiriart, R.; Hirota, A.; Hodge, J. A.; Impellizzeri, C. M. V.; Kern, J.; Kneissl, R.; Liuzzo, E.; Marcelino, N.; Marson, R.; Mignano, A.; Nakanishi, K.; Nikolic, B.; Perez, J. E.; Pérez, L. M.; Toledo, I.; Aladro, R.; Butler, B.; Cortes, J.; Cortes, P.; Dhawan, V.; Di Francesco, J.; Espada, D.; Galarza, F.; Garcia-Appadoo, D.; Guzman-Ramirez, L.; Humphreys, E. M.; Jung, T.; Kameno, S.; Laing, R. A.; Leon, S.; Mangum, J.; Marconi, G.; Nagai, H.; Nyman, L.-A.; Radiszcz, M.; Rodón, J. A.; Sawada, T.; Takahashi, S.; Tilanus, R. P. J.; van Kempen, T.; Vila Vilaro, B.; Watson, L. C.; Wiklind, T.; Gueth, F.; Tatematsu, K.; Wootten, A.; Castro-Carrizo, A.; Chapillon, E.; Dumas, G.; de Gregorio-Monsalvo, I.; Francke, H.; Gallardo, J.; Garcia, J.; Gonzalez, S.; Hibbard, J. E.; Hill, T.; Kaminski, T.; Karim, A.; Krips, M.; Kurono, Y.; Lopez, C.; Martin, S.; Maud, L.; Morales, F.; Pietu, V.; Plarre, K.; Schieven, G.; Testi, L.; Videla, L.; Villard, E.; Whyborn, N.; Alves, F.; Andreani, P.; Avison, A.; Barta, M.; Bedosti, F.; Bendo, G. J.; Bertoldi, F.; Bethermin, M.; Biggs, A.; Boissier, J.; Brand, J.; Burkutean, S.; Casasola, V.; Conway, J.; Cortese, L.; Dabrowski, B.; Davis, T. A.; Diaz Trigo, M.; Fontani, F.; Franco-Hernandez, R.; Fuller, G.; Galvan Madrid, R.; Giannetti, A.; Ginsburg, A.; Graves, S. F.; Hatziminaoglou, E.; Hogerheijde, M.; Jachym, P.; Jimenez Serra, I.; Karlicky, M.; Klaasen, P.; Kraus, M.; Kunneriath, D.; Lagos, C.; Longmore, S.; Leurini, S.; Maercker, M.; Magnelli, B.; Marti Vidal, I.; Massardi, M.; Maury, A.; Muehle, S.; Muller, S.; Muxlow, T.; O’Gorman, E.; Paladino, R.; Petry, D.; Pineda, J.; Randall, S.; Richer, J. S.; Rossetti, A.; Rushton, A.; Rygl, K.; Sanchez Monge, A.; Schaaf, R.; Schilke, P.; Stanke, T.; Schmalzl, M.; Stoehr, F.; Urban, S.; van Kampen, E.; Vlemmings, W.; Wang, K.; Wild, W.; Yang, Y.; Iguchi, S.; Hasegawa, T.; Saito, M.; Inatani, J.; Mizuno, N.; Asayama, S.; Kosugi, G.; Morita, K.-I.; Chiba, K.; Kawashima, S.; Okumura, S. K.; Ohashi, N.; Ogasawara, R.; Sakamoto, S.; Noguchi, T.; Huang, Y.-D.; Liu, S.-Y.; Kemper, F.; Koch, P. M.; Chen, M.-T.; Chikada, Y.; Hiramatsu, M.; Iono, D.; Shimojo, M.; Komugi, S.; Kim, J.; Lyo, A.-R.; Muller, E.; Herrera, C.; Miura, R. E.; Ueda, J.; Chibueze, J.; Su, Y.-N.; Trejo-Cruz, A.; Wang, K.-S.; Kiuchi, H.; Ukita, N.; Sugimoto, M.; Kawabe, R.; Hayashi, M.; Miyama, S.; Ho, P. T. P.; Kaifu, N.; Ishiguro, M.; Beasley, A. J.; Bhatnagar, S.; Braatz, J. A., III; Brisbin, D. G.; Brunetti, N.; Carilli, C.; Crossley, J. H.; D’Addario, L.; Donovan Meyer, J. L.; Emerson, D. T.; Evans, A. S.; Fisher, P.; Golap, K.; Griffith, D. M.; Hale, A. E.; Halstead, D.; Hardy, E. J.; Hatz, M. C.; Holdaway, M.; Indebetouw, R.; Jewell, P. R.; Kepley, A. A.; Kim, D.-C.; Lacy, M. D.; Leroy, A. K.; Liszt, H. S.; Lonsdale, C. J.; Matthews, B.; McKinnon, M.; Mason, B. S.; Moellenbrock, G.; Moullet, A.; Myers, S. T.; Ott, J.; Peck, A. B.; Pisano, J.; Radford, S. J. E.; Randolph, W. T.; Rao Venkata, U.; Rawlings, M. G.; Rosen, R.; Schnee, S. L.; Scott, K. S.; Sharp, N. K.; Sheth, K.; Simon, R. S.; Tsutsumi, T.; Wood, S. J.

    2015-01-01

    A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ∼15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried

  12. Adapting the M3 Surveillance Metrics for an Unknown Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, Michael Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Abes, Jeff I. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Jaramillo, Brandon Michael Lee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-11-30

    The original M3 surveillance metrics assume that the baseline is known. In this article, adapted M3 metrics are presented when the baseline is not known and estimated by available data. Deciding on how much available data is enough is also discussed.

  13. 77 FR 26535 - Hope Gas, Inc.; Notice of Baseline Filing

    Science.gov (United States)

    2012-05-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Hope Gas, Inc.; Notice of Baseline Filing Take notice that on April 26, 2012, Hope Gas, Inc. (Hope Gas) submitted a baseline filing of their Statement of Operating Conditions...

  14. 77 FR 31841 - Hope Gas, Inc.; Notice of Baseline Filing

    Science.gov (United States)

    2012-05-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Hope Gas, Inc.; Notice of Baseline Filing Take notice that on May 16, 2012, Hope Gas, Inc. (Hope Gas) submitted a revised baseline filing of their Statement of...

  15. APOC impact assessment studies: baseline ophthalmological findings in Morogoro, Tanzania.

    Science.gov (United States)

    Babalola, O E; Maegga, B; Katenga, S; Ogbuagu, F K; Umeh, R E; Seketeli, E; Braide, E

    2008-12-01

    The goal of the African Programme for Onchocerciasis Control (APOC) is to eliminate Onchocerciasis as a disease of public Health significance and an important constraint to socio-economic development in the 19 none OCP (Onchocerciasis Control Project) countries covered through Community-Directed Treatment with Ivermectin, CDTI. In 1998, impact assessment studies were carried out in Morogoro, Tanzania during which baseline ophthalmological parameters were established. The hypothesis being tested is that CDTI will prevent or delay progression of onchocercal eye lesions and blindness. A total of 425 subjects aged 10 years or more from 14 villages within Bwakira district ofMorogoro region in Tanzania were examined for Snellen visual acuity, ocular microfilaria, lens opacities, uveitis and posterior segment disease especially chorioretinitis and optic nerve disease. Motion Sensitivity Screening Test (MSST) was carried out as well. Microfilaria was present in the anterior chamber of nearly half (49.2%) of all subjects examined. Prevalence of blindness was extremely high at 15.2%. Onchocercal lesions were responsible for blindness in 41.5% of these, followed by cataracts (27.7%), glaucoma (10.8%) and trachoma (6.2%). The main pathway to onchocercal blindness in this population was anterior uveitis with or without secondary cataracts. There is an urgent need to get CDTI underway and institute other horizontal primary eye care measures, especially cataract backlog reduction, in order to reduce the excessive burden of avoidable blindness in this community.

  16. Idaho National Laboratory’s Greenhouse Gas FY08 Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Jennifer D. Morton

    2011-06-01

    A greenhouse gas (GHG) inventory is a systematic attempt to account for the production and release of certain gasses generated by an institution from various emission sources. The gasses of interest are those which have become identified by climate science as related to anthropogenic global climate change. This document presents an inventory of GHGs generated during fiscal year (FY) 2008 by Idaho National Laboratory (INL), a Department of Energy (DOE)-sponsored entity, located in southeastern Idaho. Concern about the environmental impact of GHGs has grown in recent years. This, together with a desire to decrease harmful environmental impacts, would be enough to encourage the calculation of a baseline estimate of total GHGs generated at INL. Additionally, INL has a desire to see how its emissions compare with similar institutions, including other DOE national laboratories. Executive Order 13514 requires that federal agencies and institutions document reductions in GHG emissions in the future, and such documentation will require knowledge of a baseline against which reductions can be measured. INL's FY08 GHG inventory was calculated according to methodologies identified in federal GHG guidance documents using operational control boundaries. It measures emissions generated in three Scopes: (1) INL emissions produced directly by stationary or mobile combustion and by fugitive emissions, (2) the share of emissions generated by entities from which INL purchased electrical power, and (3) indirect or shared emissions generated by outsourced activities that benefit INL (occur outside INL's organizational boundaries but are a consequence of INL's activities). This inventory found that INL generated a total of 113,049 MT of CO2-equivalent emissions during FY08. The following conclusions were made from looking at the results of the individual contributors to INL's baseline GHG inventory: (1) Electricity (including the associated transmission and

  17. Idaho National Laboratory’s Greenhouse Gas FY08 Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Jennifer D. Morton

    2010-09-01

    s baseline GHG inventory: • Electricity is the largest contributor to INL’s GHG inventory, with over 50% of the net anthropogenic CO2e emissions • Other sources with high emissions were stationary combustion, fugitive emissions from the onsite landfill, mobile combustion (fleet fuels) and the employee commute • Sources with low emissions were contracted waste disposal, wastewater treatment (onsite and contracted) and fugitive emissions from refrigerants. This report details the methods behind quantifying INL’s GHG inventory and discusses lessons learned on better practices by which information important to tracking GHGs can be tracked and recorded. It is important to stress that the methodology behind this inventory followed guidelines that have not yet been formally adopted. Thus, some modification of the conclusions may be necessary as additional guidance is received. Further, because this report differentiates between those portions of the INL that are managed and operated by the Battelle Energy Alliance (BEA) and those managed by other contractors, it includes only that large proportion of Laboratory activities overseen by BEA. It is assumed that other contractors will provide similar reporting for those activities they manage, where appropriate.

  18. The MINK methodology: background and baseline. [USA - Midwest Region

    Energy Technology Data Exchange (ETDEWEB)

    Rosenberg, N.J.; Crosson, P.R.; Frederick, K.D.; Easterling, W.E. III; McKenney, M.S.; Bowes, M.D.; Sedjo, R.A.; Darmstadter, J.; Katz, L.A.; Lemon, K.M. (Resources for the Future, Washington, DC (United States))

    1993-06-01

    A four step methodology has been developed for study of the regional impacts of climate change and the possible responses thereto. First the region's climate sensitive sectors and total economy are described (Task A, current baseline). Next a scenario of climate change is imposed on the current baseline (Task B, current baseline with climate change). A new baseline describing the climate sensitive sectors and total regional economy is projected for some time in the future (Task C, future baseline, year 2030) in the absence of climate change. Finally, the climate change scenario is reimposed on the future baseline (Task D, future baseline with climate change). Impacts of the climate change scenario on the current and future regional economies are determined by means of simulation models and other appropriate techniques. These techniques are also used to assess the impacts of an elevated CO[sub 2] concentration (450 ppm) and of various forms of adjustments and adaptations. The region chosen for the first test of the methodology is composed of the four U.S. states of Missouri, Iowa, Nebraska and Kansas. The climate change scenario is the actual weather of the 1930s decade in the MINK region. 'Current' climate is the actual weather of the period 1951-1980. 20 refs., 3 figs., 2 tabs.

  19. Sustainability of a successful malaria surveillance and treatment program in a Runggus community in Sabah, east Malaysia.

    Science.gov (United States)

    Hii, J L; Chee, K C; Vun, Y S; Awang, J; Chin, K H; Kan, S K

    1996-09-01

    The district of Kudat has one of the highest and most persistent malaria transmission levels in Sabah, Malaysia, with annual parasite incidence of 102 per 1,000 inhabitants per year. Due to this situation and the failure of DDT spraying to control malaria, a community participation health program (Sukarelawan Penjagaan Kesihatan Primer or SPKP) was developed as an adjunct to current anti-malarial measures during 1987-1991. SPKP is made up of unpaid community workers known as village health volunteers (VHVs). VHVs are selected by a village development and security committees training and supervision a member of the Vector-Borne Diseases Control Program (VBDCP). The beneficiaries of SPKP consisted primarily of Runggus people and other remote, and mobile populations who visit the home of a VHV for diagnosis and treatment. This group of febrile patients and their children who attend a participating school submit finger prick blood and personal details to the VHV. and receive a presumptive treatment for malaria. Thick and thin blood smears are examined by a VBDCP microscopist who then prepare and forward a radical or curative treatment to the VHV so that it can be administered to the microscopically-positive patient free of charge. Between June 1987 to June 1991, VHVs from 32 kampungs (villages) and 22 schools collected 56,245 slides representing 24.7% of total slide collection compared to 74.9% collected by passive case detection (PCD) posts in health centers and district hospital. The average volunteer treated 11.8 (range 10.4-13.4) and 31.4 (range 26-49) patients per month in kampungs and schools respectively. In contrast, non-SPKP posts in a district hospital, health centers and flying doctor service treated an average of 616.3 patients per month (range 134.8-1032.8). The slide positivity rate of blood smears taken by VHVs was 8.43% compared with 7.37% for non-SPKP posts. Average slide collection and slide positivity rates varied considerably from one community to

  20. Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas

    Directory of Open Access Journals (Sweden)

    Massougbodji Achille

    2007-12-01

    Full Text Available Abstract Malaria in pregnancy is one of the major causes of maternal morbidity and adverse birth outcomes. In high transmission areas, its prevention has recently changed, moving from a weekly or bimonthly chemoprophylaxis to intermittent preventive treatment (IPTp. IPTp consists in the administration of a single curative dose of an efficacious anti-malarial drug at least twice during pregnancy – regardless of whether the woman is infected or not. The drug is administered under supervision during antenatal care visits. Sulphadoxine-pyrimethamine (SP is the drug currently recommended by the WHO. While SP-IPTp seems an adequate strategy, there are many issues still to be explored to optimize it. This paper reviewed data on IPTp efficacy and discussed how to improve it. In particular, the determination of both the optimal number of doses and time of administration of the drug is essential, and this has not yet been done. As both foetal growth and deleterious effects of malaria are maximum in late pregnancy women should particularly be protected during this period. Monitoring of IPTp efficacy should be applied to all women, and not only to primi- and secondigravidae, as it has not been definitively established that multigravidae are not at risk for malaria morbidity and mortality. In HIV-positive women, there is an urgent need for specific information on drug administration patterns (need for higher doses, possible interference with sulpha-based prophylaxis of opportunistic infections. Because of the growing level of resistance of parasites to SP, alternative drugs for IPTp are urgently needed. Mefloquine is presently one of the most attractive options because of its long half life, high efficacy in sub-Saharan Africa and safety during pregnancy. Also, efforts should be made to increase IPTp coverage by improving the practices of health care workers, the motivation of women and their perception of malaria complications in pregnancy. Because IPTp

  1. Neutrino oscillations: what is magic about the "magic" baseline?

    CERN Document Server

    Smirnov, A Yu

    2006-01-01

    Physics interpretation of the ``magic'' baseline that can play important role in future oscillation experiments is given. The ``magic'' baseline coincides with the refraction length, $l_0$. The latter, in turn, approximately equals the oscillation length in matter at high energies. Therefore at the baseline $L = l_0$ the oscillation phase is $2\\pi$, and consequently, the ``solar'' amplitude of oscillations driven by the mixing angle $\\theta_{12}$ and mass splitting $\\Delta m^2_{21}$ vanishes. As a result, in the lowest order (i) the interference of amplitudes in the $\

  2. Trinocular Stereo Matching Based on Correlations Between Baselines and Disparities

    Institute of Scientific and Technical Information of China (English)

    GUANYepeng; GUWeikang

    2004-01-01

    Gray correlation technique is utilized to take the multi-peak feature points with gray correlation coefficients less than a certain range of maximal correlation coefficient as a potential candidate matching set. There exists the maximal correlation between the correct disparities and their corresponding baselines. A trinocular stereo matching algorithm is proposed based on correlations between the baselines and disparities. After computing the correlations between the baselines and disparities, the unique matches can be determined by maximal correlation coefficient. It is proved that the algorithm proposed is valid and credible by 3-D reconstruction on two pairs of actual natural stereo images.

  3. Study of space shuttle orbiter system management computer function. Volume 1: Analysis, baseline design

    Science.gov (United States)

    1975-01-01

    A system analysis of the shuttle orbiter baseline system management (SM) computer function is performed. This analysis results in an alternative SM design which is also described. The alternative design exhibits several improvements over the baseline, some of which are increased crew usability, improved flexibility, and improved growth potential. The analysis consists of two parts: an application assessment and an implementation assessment. The former is concerned with the SM user needs and design functional aspects. The latter is concerned with design flexibility, reliability, growth potential, and technical risk. The system analysis is supported by several topical investigations. These include: treatment of false alarms, treatment of off-line items, significant interface parameters, and a design evaluation checklist. An in-depth formulation of techniques, concepts, and guidelines for design of automated performance verification is discussed.

  4. Baseline hospital performance and the impact of medical emergency teams: Modelling vs. conventional subgroup analysis

    Directory of Open Access Journals (Sweden)

    Hillman Ken

    2009-12-01

    Full Text Available Abstract Background To compare two approaches to the statistical analysis of the relationship between the baseline incidence of adverse events and the effect of medical emergency teams (METs. Methods Using data from a cluster randomized controlled trial (the MERIT study, we analysed the relationship between the baseline incidence of adverse events and its change from baseline to the MET activation phase using quadratic modelling techniques. We compared the findings with those obtained with conventional subgroup analysis. Results Using linear and quadratic modelling techniques, we found that each unit increase in the baseline incidence of adverse events in MET hospitals was associated with a 0.59 unit subsequent reduction in adverse events (95%CI: 0.33 to 0.86 after MET implementation and activation. This applied to cardiac arrests (0.74; 95%CI: 0.52 to 0.95, unplanned ICU admissions (0.56; 95%CI: 0.26 to 0.85 and unexpected deaths (0.68; 95%CI: 0.45 to 0.90. Control hospitals showed a similar reduction only for cardiac arrests (0.95; 95%CI: 0.56 to 1.32. Comparison using conventional subgroup analysis, on the other hand, detected no significant difference between MET and control hospitals. Conclusions Our study showed that, in the MERIT study, when there was dependence of treatment effect on baseline performance, an approach based on regression modelling helped illustrate the nature and magnitude of such dependence while sub-group analysis did not. The ability to assess the nature and magnitude of such dependence may have policy implications. Regression technique may thus prove useful in analysing data when there is a conditional treatment effect.

  5. Relationships Between Metabolic Syndrome and Other Baseline Factors and the Efficacy of Ezetimibe/Simvastatin and Atorvastatin in Patients With Type 2 Diabetes and Hypercholesterolemia

    Science.gov (United States)

    Goldberg, Ronald B.; Guyton, John R.; Mazzone, Theodore; Weinstock, Ruth S.; Polis, Adam B.; Tipping, Diane; Tomassini, Joanne E.; Tershakovec, Andrew M.

    2010-01-01

    OBJECTIVE To investigate relationships between baseline factors and treatment-associated efficacy changes in type 2 diabetes. RESEARCH DESIGN AND METHODS Multivariable analyses of treatment response in 1,229 type 2 diabetic patients with hypercholesterolemia who received ezetimibe/simvastatin or atorvastatin in a randomized double-blind 6-week study. RESULTS Increasing age was related to improvements in all lipid assessments. Men had greater triglyceride and non-HDL cholesterol reductions than women, and black/Hispanic patients had less favorable lipid effects than other races/ethnicities. Increasing baseline LDL cholesterol was associated with improvements in most lipids; higher baseline non-HDL cholesterol with improved HDL cholesterol and triglycerides; higher baseline HDL cholesterol with greater non-HDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) reductions; and higher baseline hs-CRP with smaller LDL cholesterol, non-HDL cholesterol, and apolipoprotein B reductions. Patients with high baseline non-HDL cholesterol or triglycerides less frequently attained LDL cholesterol targets. Obesity was inversely related to HDL cholesterol and hs-CRP changes, and higher baseline A1C to smaller apolipoprotein B reductions. Metabolic syndrome was not a significant predictor. CONCLUSIONS Treatment responses in type 2 diabetic patients were related to baseline factors, although treatment effects (ezetimibe/simvastatin being more effective than atorvastatin) remained consistent. The presence of predictive factors should be considered in planning lipid-altering therapy. PMID:20150290

  6. Baseline inventory data recommendations for National Wildlife Refuges

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Baseline Inventory Team recommends that each refuge have available abiotic “data layers” for topography, aerial photography, hydrography, soils, boundaries, and...

  7. Baseline inventory data users guide to abiotic GIS layers

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Baseline Inventory Team was chartered by the Fulfilling the Promises Implementation Team to recommend minimum abiotic and biotic inventories for the National...

  8. Sterile Neutrino Fits to Short-Baseline Neutrino Oscillation Measurements

    Directory of Open Access Journals (Sweden)

    J. M. Conrad

    2013-01-01

    (3 + 2 and (3 + 3 fits, rather than (3 + 1 fits, for future neutrino oscillation phenomenology. These results motivate the pursuit of further short-baseline experiments, such as those reviewed in this paper.

  9. Baseline assessment of fish communities of the Flower Garden Banks

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The work developed baseline information on fish and benthic communities within the Flower Garden Banks National Marine Sanctuary (FGBNMS). Surveys employed diving,...

  10. Baseline vegetation mapping : Fort Niobrara National Wildlife Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Final report for the baseline vegetation mapping project on Fort Niobrara National Wildlife Refuge. This project aims to create a vegetation map showing the...

  11. Butler Hollow Glades : Baseline assessment and vegetation monitoring establishment

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Several sampling and documentation protocols were implemented to establish baseline vegetation data. These data will provide a comparison point for future...

  12. 40 CFR 80.93 - Individual baseline submission and approval.

    Science.gov (United States)

    2010-07-01

    ...: (i) Refinery block flow diagram, showing principal refining units; (ii) Principal refining unit... parameter for which a baseline value is required, per § 80.91: (i) Narrative of the development of...

  13. Information architecture. Volume 2, Part 1: Baseline analysis summary

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    The Department of Energy (DOE) Information Architecture, Volume 2, Baseline Analysis, is a collaborative and logical next-step effort in the processes required to produce a Departmentwide information architecture. The baseline analysis serves a diverse audience of program management and technical personnel and provides an organized way to examine the Department`s existing or de facto information architecture. A companion document to Volume 1, The Foundations, it furnishes the rationale for establishing a Departmentwide information architecture. This volume, consisting of the Baseline Analysis Summary (part 1), Baseline Analysis (part 2), and Reference Data (part 3), is of interest to readers who wish to understand how the Department`s current information architecture technologies are employed. The analysis identifies how and where current technologies support business areas, programs, sites, and corporate systems.

  14. Seier NWR second year baseline CCP preparation surveys

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Final report for a project to collect baseline biological information on John W. And Louise Seier National Wildlife Refuge, to aid in preparation of 2014...

  15. LBCS: The LOFAR Long-Baseline Calibrator Survey

    Science.gov (United States)

    Jackson, N.; Tagore, A.; Deller, A.; Moldón, J.; Varenius, E.; Morabito, L.; Wucknitz, O.; Carozzi, T.; Conway, J.; Drabent, A.; Kapinska, A.; Orrù, E.; Brentjens, M.; Blaauw, R.; Kuper, G.; Sluman, J.; Schaap, J.; Vermaas, N.; Iacobelli, M.; Cerrigone, L.; Shulevski, A.; ter Veen, S.; Fallows, R.; Pizzo, R.; Sipior, M.; Anderson, J.; Avruch, I. M.; Bell, M. E.; van Bemmel, I.; Bentum, M. J.; Best, P.; Bonafede, A.; Breitling, F.; Broderick, J. W.; Brouw, W. N.; Brüggen, M.; Ciardi, B.; Corstanje, A.; de Gasperin, F.; de Geus, E.; Eislöffel, J.; Engels, D.; Falcke, H.; Garrett, M. A.; Grießmeier, J. M.; Gunst, A. W.; van Haarlem, M. P.; Heald, G.; Hoeft, M.; Hörandel, J.; Horneffer, A.; Intema, H.; Juette, E.; Kuniyoshi, M.; van Leeuwen, J.; Loose, G. M.; Maat, P.; McFadden, R.; McKay-Bukowski, D.; McKean, J. P.; Mulcahy, D. D.; Munk, H.; Pandey-Pommier, M.; Polatidis, A. G.; Reich, W.; Röttgering, H. J. A.; Rowlinson, A.; Scaife, A. M. M.; Schwarz, D. J.; Steinmetz, M.; Swinbank, J.; Thoudam, S.; Toribio, M. C.; Vermeulen, R.; Vocks, C.; van Weeren, R. J.; Wise, M. W.; Yatawatta, S.; Zarka, P.

    2016-11-01

    We outline the LOFAR Long-Baseline Calibrator Survey (LBCS), whose aim is to identify sources suitable for calibrating the highest-resolution observations made with the International LOFAR Telescope, which include baselines >1000 km. Suitable sources must contain significant correlated flux density (≳ 50 - 100 mJy) at frequencies around 110-190 MHz on scales of a few hundred milliarcseconds. At least for the 200-300-km international baselines, we find around 1 suitable calibrator source per square degree over a large part of the northern sky, in agreement with previous work. This should allow a randomly selected target to be successfully phase calibrated on the international baselines in over 50% of cases. Products of the survey include calibrator source lists and fringe-rate and delay maps of wide areas - typically a few degrees - around each source. The density of sources with significant correlated flux declines noticeably with baseline length over the range 200-600 km, with good calibrators on the longest baselines appearing only at the rate of 0.5 per sq. deg. Coherence times decrease from 1-3 min on 200-km baselines to about 1 min on 600-km baselines, suggesting that ionospheric phase variations contain components with scales of a few hundred kilometres. The longest median coherence time, at just over 3 min, is seen on the DE609 baseline, which at 227 km is close to being the shortest. We see median coherence times of between 80 and 110 s on the four longest baselines (580-600 km), and about 2 min for the other baselines. The success of phase transfer from calibrator to target is shown to be influenced by distance, in a manner that suggests a coherence patch at 150-MHz of the order of 1 deg. Although source structures cannot be measured in these observations, we deduce that phase transfer is affected if the calibrator source structure is not known. We give suggestions for calibration strategies and choice of calibrator sources, and describe the access to

  16. Fusion of a Variable Baseline System and a Range Finder

    Directory of Open Access Journals (Sweden)

    Rafael Arnay

    2011-12-01

    Full Text Available One of the greatest difficulties in stereo vision is the appearance of ambiguities when matching similar points from different images. In this article we analyze the effectiveness of using a fusion of multiple baselines and a range finder from a theoretical point of view, focusing on the results of using both prismatic and rotational articulations for baseline generation, and offer a practical case to prove its efficiency on an autonomous vehicle.

  17. MALDI-TOF Baseline Drift Removal Using Stochastic Bernstein Approximation

    Directory of Open Access Journals (Sweden)

    Howard Daniel

    2006-01-01

    Full Text Available Stochastic Bernstein (SB approximation can tackle the problem of baseline drift correction of instrumentation data. This is demonstrated for spectral data: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF data. Two SB schemes for removing the baseline drift are presented: iterative and direct. Following an explanation of the origin of the MALDI-TOF baseline drift that sheds light on the inherent difficulty of its removal by chemical means, SB baseline drift removal is illustrated for both proteomics and genomics MALDI-TOF data sets. SB is an elegant signal processing method to obtain a numerically straightforward baseline shift removal method as it includes a free parameter that can be optimized for different baseline drift removal applications. Therefore, research that determines putative biomarkers from the spectral data might benefit from a sensitivity analysis to the underlying spectral measurement that is made possible by varying the SB free parameter. This can be manually tuned (for constant or tuned with evolutionary computation (for .

  18. THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW

    Energy Technology Data Exchange (ETDEWEB)

    Partnership, ALMA [Astrophysics Research Institute, Liverpool John Moores University, IC2, Liverpool Science Park, 146 Brownlow Hill, Liverpool L3 5RF (United Kingdom); Fomalont, E. B.; Vlahakis, C.; Corder, S.; Remijan, A.; Barkats, D.; Dent, W. R. F.; Phillips, N.; Cox, P.; Hales, A. S. [Joint ALMA Observatory, Alonso de Córdova 3107, Vitacura, Santiago (Chile); Lucas, R. [Institut de Planétologie et d’Astrophysique de Grenoble (UMR 5274), BP 53, F-38041 Grenoble Cedex 9 (France); Hunter, T. R.; Brogan, C. L.; Amestica, R.; Cotton, W. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Asaki, Y. [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Matsushita, S. [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 106, Taiwan (China); Hills, R. E. [Astrophysics Group, Cavendish Laboratory, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Richards, A. M. S. [Jodrell Bank Centre for Astrophysics, School of Physics and Astronomy, University of Manchester, Oxford Road, Manchester M13 9PL (United Kingdom); Broguiere, D., E-mail: efomalon@nrao.edu [Institut de Radioastronomie Millime´trique (IRAM), 300 rue de la Piscine, Domaine Universitaire, F-38406 Saint Martin d’Hères (France); and others

    2015-07-20

    A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ∼15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ∼350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.

  19. Precise baseline determination for the TanDEM-X mission

    Science.gov (United States)

    Koenig, Rolf; Moon, Yongjin; Neumayer, Hans; Wermuth, Martin; Montenbruck, Oliver; Jäggi, Adrian

    The TanDEM-X mission will strive for generating a global precise Digital Elevation Model (DEM) by way of bi-static SAR in a close formation of the TerraSAR-X satellite, already launched on June 15, 2007, and the TanDEM-X satellite to be launched in May 2010. Both satellites carry the Tracking, Occultation and Ranging (TOR) payload supplied by the GFZ German Research Centre for Geosciences. The TOR consists of a high-precision dual-frequency GPS receiver, called Integrated GPS Occultation Receiver (IGOR), and a Laser retro-reflector (LRR) for precise orbit determination (POD) and atmospheric sounding. The IGOR is of vital importance for the TanDEM-X mission objectives as the millimeter level determination of the baseline or distance between the two spacecrafts is needed to derive meter level accurate DEMs. Within the TanDEM-X ground segment GFZ is responsible for the operational provision of precise baselines. For this GFZ uses two software chains, first its Earth Parameter and Orbit System (EPOS) software and second the BERNESE software, for backup purposes and quality control. In a concerted effort also the German Aerospace Center (DLR) generates precise baselines independently with a dedicated Kalman filter approach realized in its FRNS software. By the example of GRACE the generation of baselines with millimeter accuracy from on-board GPS data can be validated directly by way of comparing them to the intersatellite K-band range measurements. The K-band ranges are accurate down to the micrometer-level and therefore may be considered as truth. Both TanDEM-X baseline providers are able to generate GRACE baselines with sub-millimeter accuracy. By merging the independent baselines by GFZ and DLR, the accuracy can even be increased. The K-band validation however covers solely the along-track component as the K-band data measure just the distance between the two GRACE satellites. In addition they inhibit an un-known bias which must be modelled in the comparison, so the

  20. Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Diallo Mouctar

    2009-06-01

    most national policies plan to strengthen malaria control to reach the elimination of this disease, anti-malarial drugs such as the artesunate + amodiaquine fixed-dose ACT will play a pivotal role in this process. Trial registration The protocol was registered with the www.clinicaltrials.gov open clinical trial registry under the identifier number NCT00316329.

  1. Atmospheric pressure loading parameters from very long baseline interferometry observations

    Science.gov (United States)

    Macmillan, D. S.; Gipson, John M.

    1994-01-01

    Atmospheric mass loading produces a primarily vertical displacement of the Earth's crust. This displacement is correlated with surface pressure and is large enough to be detected by very long baseline interferometry (VLBI) measurements. Using the measured surface pressure at VLBI stations, we have estimated the atmospheric loading term for each station location directly from VLBI data acquired from 1979 to 1992. Our estimates of the vertical sensitivity to change in pressure range from 0 to -0.6 mm/mbar depending on the station. These estimates agree with inverted barometer model calculations (Manabe et al., 1991; vanDam and Herring, 1994) of the vertical displacement sensitivity computed by convolving actual pressure distributions with loading Green's functions. The pressure sensitivity tends to be smaller for stations near the coast, which is consistent with the inverted barometer hypothesis. Applying this estimated pressure loading correction in standard VLBI geodetic analysis improves the repeatability of estimated lengths of 25 out of 37 baselines that were measured at least 50 times. In a root-sum-square (rss) sense, the improvement generally increases with baseline length at a rate of about 0.3 to 0.6 ppb depending on whether the baseline stations are close to the coast. For the 5998-km baseline from Westford, Massachusetts, to Wettzell, Germany, the rss improvement is about 3.6 mm out of 11.0 mm. The average rss reduction of the vertical scatter for inland stations ranges from 2.7 to 5.4 mm.

  2. Detection of abrupt baseline length changes using cumulative sums

    Science.gov (United States)

    Janssen, Volker

    2009-06-01

    Dynamic processes are usually monitored by collecting a time series of observations, which is then analysed in order to detect any motion or non-standard behaviour. Geodetic examples include the monitoring of dams, bridges, high-rise buildings, landslides, volcanoes and tectonic motion. The cumulative sum (CUSUM) test is recognised as a popular means to detect changes in the mean and/or the standard deviation of a time series and has been applied to various monitoring tasks. This paper briefly describes the CUSUM technique and how it can be utilised for the detection of small baseline length changes by differencing two perpendicular baselines sharing a common site. A simulation is carried out in order to investigate the expected behaviour of the resulting CUSUM charts for a variety of typical deformation monitoring scenarios. This simulation shows that using first differences (between successive epochs) as input, rather than the original baseline lengths, produces clear peaks or jumps in the differenced CUSUM time series when a sudden change in baseline length occurs. These findings are validated by analysing several GPS baseline pairs of a network deployed to monitor the propagation of an active ice shelf rift on the Amery Ice Shelf, East Antarctica.

  3. Combined GPS + BDS for short to long baseline RTK positioning

    Science.gov (United States)

    Odolinski, R.; Teunissen, P. J. G.; Odijk, D.

    2015-04-01

    The BeiDou Navigation Satellite System (BDS) has become fully operational in the Asia-Pacific region and it is of importance to evaluate what BDS brings when combined with the Global Positioning System (GPS). In this contribution we will look at the short, medium and long single-baseline real-time kinematic (RTK) positioning performance. Short baseline refers to when the distance between the two receivers is at most a few kilometers so that the relative slant ionospheric and tropospheric delays can be assumed absent, whereas with medium baseline we refer to when the uncertainty of these ionospheric delays can reliably be modeled as a function of the baseline length. With long baseline we refer to the necessity to parameterize the ionospheric delays and (wet) Zenith Tropospheric Delay (ZTD) as completely unknown. The GNSS real data are collected in Perth, Australia. It will be shown that combining the two systems allows for the use of higher than customary elevation cut-off angles. This can be of particular benefit in environments with restricted satellite visibility such as in open pit mines or urban canyons.

  4. LBCS: the LOFAR Long-Baseline Calibrator Survey

    CERN Document Server

    Jackson, N; Deller, A; Moldón, J; Varenius, E; Morabito, L; Wucknitz, O; Carozzi, T; Conway, J; Drabent, A; Kapinska, A; Orrù, E; Brentjens, M; Blaauw, R; Kuper, G; Sluman, J; Schaap, J; Vermaas, N; Iacobelli, M; Cerrigone, L; Shulevski, A; ter Veen, S; Fallows, R; Pizzo, R; Sipior, M; Anderson, J; Avruch, M; Bell, M; van Bemmel, I; Bentum, M; Best, P; Bonafede, A; Breitling, F; Broderick, J; Brouw, W; Brüggen, M; Ciardi, B; Corstanje, A; de Gasperin, F; de Geus, E; Eislöffel, J; Engels, D; Falcke, H; Garrett, M; Griessmeier, J; Gunst, A; van Haarlem, M; Heald, G; Hoeft, M; Hörandel, J; Horneffer, A; Intema, H; Juette, E; Kuniyoshi, M; van Leeuwen, J; Loose, G; Maat, P; McFadden, R; McKay-Bukowski, D; McKean, J; Mulcahy, D; Munk, H; Pandey-Pommier, M; Polatidis, A; Reich, W; Röttgering, H; Rowlinson, A; Scaife, A; Schwarz, D; Steinmetz, M; Swinbank, J; Thoudam, S; Toribio, M; Vermeulen, R; Vocks, C; van Weeren, R; Wise, M; Yatawatta, S; Zarka, P

    2016-01-01

    (abridged). We outline LBCS (the LOFAR Long-Baseline Calibrator Survey), whose aim is to identify sources suitable for calibrating the highest-resolution observations made with the International LOFAR Telescope, which include baselines >1000 km. Suitable sources must contain significant correlated flux density (50-100mJy) at frequencies around 110--190~MHz on scales of a few hundred mas. At least for the 200--300-km international baselines, we find around 1 suitable calibrator source per square degree over a large part of the northern sky, in agreement with previous work. This should allow a randomly selected target to be successfully phase calibrated on the international baselines in over 50% of cases. Products of the survey include calibrator source lists and fringe-rate and delay maps of wide areas -- typically a few degrees -- around each source. The density of sources with significant correlated flux declines noticeably with baseline length over the range 200--600~km, with good calibrators on the longest...

  5. Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

    Directory of Open Access Journals (Sweden)

    Khatib Rashid A

    2012-04-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS co-administered with SP (AS + SP, was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from Interpretation The introduction of ACT at

  6. Coverage, adherence and costs of intermittent preventive treatment of malaria in children employing different delivery strategies in Jasikan, Ghana.

    Directory of Open Access Journals (Sweden)

    Edith Patouillard

    Full Text Available BACKGROUND: Intermittent preventive treatment of malaria in children (IPTc involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected. IPTc provides a high level of protection against uncomplicated and severe malaria, with monthly sulphadoxine-pyrimethamine plus amodiaquine (SP&AQ and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens. A key challenge is the identification of a cost-effective delivery strategy. METHODS: A community randomized trial was undertaken in Jasikan district, Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways. Twelve villages were randomly selected to receive IPTc from village health workers (VHWs or facility-based nurses working at health centres' outpatient departments (OPD or EPI outreach clinics. Children aged 3 to 59 months-old received one IPT course (three doses in May, June, September and October. Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective. RESULTS: The economic cost per child receiving at least the first dose of all 4 courses was US$4.58 when IPTc was delivered by VHWs, US$4.93 by OPD nurses and US$ 5.65 by EPI nurses. The unit economic cost of receiving all 3 doses of all 4 courses was US$7.56 and US$8.51 when IPTc was delivered by VHWs or facility-based nurses respectively. The main cost driver for the VHW delivery was supervision, reflecting resources used for travelling to more remote communities rather than more intense supervision, and for OPD and EPI delivery, it was the opportunity cost of the time spent by nurses in dispensing IPTc. CONCLUSIONS: VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district

  7. Functional Testing Protocols for Commercial Building Efficiency Baseline Modeling Software

    Energy Technology Data Exchange (ETDEWEB)

    Jump, David; Price, Phillip N.; Granderson, Jessica; Sohn, Michael

    2013-09-06

    This document describes procedures for testing and validating proprietary baseline energy modeling software accuracy in predicting energy use over the period of interest, such as a month or a year. The procedures are designed according to the methodology used for public domain baselining software in another LBNL report that was (like the present report) prepared for Pacific Gas and Electric Company: ?Commercial Building Energy Baseline Modeling Software: Performance Metrics and Method Testing with Open Source Models and Implications for Proprietary Software Testing Protocols? (referred to here as the ?Model Analysis Report?). The test procedure focuses on the quality of the software?s predictions rather than on the specific algorithms used to predict energy use. In this way the software vendor is not required to divulge or share proprietary information about how their software works, while enabling stakeholders to assess its performance.

  8. A publication database for optical long baseline interferometry

    CERN Document Server

    Malbet, Fabien; Lawson, Peter; Taillifet, Esther; Lafrasse, Sylvain

    2010-01-01

    Optical long baseline interferometry is a technique that has generated almost 850 refereed papers to date. The targets span a large variety of objects from planetary systems to extragalactic studies and all branches of stellar physics. We have created a database hosted by the JMMC and connected to the Optical Long Baseline Interferometry Newsletter (OLBIN) web site using MySQL and a collection of XML or PHP scripts in order to store and classify these publications. Each entry is defined by its ADS bibcode, includes basic ADS informations and metadata. The metadata are specified by tags sorted in categories: interferometric facilities, instrumentation, wavelength of operation, spectral resolution, type of measurement, target type, and paper category, for example. The whole OLBIN publication list has been processed and we present how the database is organized and can be accessed. We use this tool to generate statistical plots of interest for the community in optical long baseline interferometry.

  9. Environmental baselines: preparing for shale gas in the UK

    Science.gov (United States)

    Bloomfield, John; Manamsa, Katya; Bell, Rachel; Darling, George; Dochartaigh, Brighid O.; Stuart, Marianne; Ward, Rob

    2014-05-01

    Groundwater is a vital source of freshwater in the UK. It provides almost 30% of public water supply on average, but locally, for example in south-east England, it is constitutes nearly 90% of public supply. In addition to public supply, groundwater has a number of other uses including agriculture, industry, and food and drink production. It is also vital for maintaining river flows especially during dry periods and so is essential for maintaining ecosystem health. Recently, there have been concerns expressed about the potential impacts of shale gas development on groundwater. The UK has abundant shales and clays which are currently the focus of considerable interest and there is active research into their characterisation, resource evaluation and exploitation risks. The British Geological Survey (BGS) is undertaking research to provide information to address some of the environmental concerns related to the potential impacts of shale gas development on groundwater resources and quality. The aim of much of this initial work is to establish environmental baselines, such as a baseline survey of methane occurrence in groundwater (National methane baseline study) and the spatial relationships between potential sources and groundwater receptors (iHydrogeology project), prior to any shale gas exploration and development. The poster describes these two baseline studies and presents preliminary findings. BGS are currently undertaking a national survey of baseline methane concentrations in groundwater across the UK. This work will enable any potential future changes in methane in groundwater associated with shale gas development to be assessed. Measurements of methane in potable water from the Cretaceous, Jurassic and Triassic carbonate and sandstone aquifers are variable and reveal methane concentrations of up to 500 micrograms per litre, but the mean value is relatively low at 2km. The geological modelling process will be presented and discussed along with maps combining

  10. Subtracting Technique of Baselines for Capillary Electrophoresis Signals

    Institute of Scientific and Technical Information of China (English)

    WANG Ying; MO Jin-yuan; CHEN Zuan-guang; GAO Yan

    2004-01-01

    The drifting baselines of capillary electrophoresis affect the veracity of analysis greatly. This paper presents Threshold Fitting Technique(TFT) so as to subtract the baselines from the original signals and emendate the signals. In TFT, wav elet and curve fitting technique are applied synthetically, thresholds are decided by the computer automatically. Many experiments of signal processing indicate that TFT is simple for being used, there are few man-induced factors, and the results are satisfactory. TFT can be applied for noisy signals without any pre-processing.

  11. EQUIVALENT BASELINE AND INTERFEROMETRIC PHASE OF CLUSTER SATELLITE SAR

    Institute of Scientific and Technical Information of China (English)

    Gong Min; Zhang Chuanwu; Huang Shunji

    2005-01-01

    The change of the equivalent baseline and interferometric phase of cluster SAR satellites is analyzed when the constellation circles around the Earth and the satellites rotate around the center at the same time. The letter provides assessment of baseline error and phase error which influence the precision of height measurement in the across-track interferometric mode. The mathematical model of cluster satellite movement is built, simulation analyses and the curve of height error are presented. The simulation results show that height measurement error can be compensated by the formulae derived in this letter, therefore, the Digital Elevation Models (DEM's) are recovered accurately.

  12. Intermediate baseline appearance experiments and three-neutrino mixing schemes

    CERN Document Server

    Cardall, C Y; Cline, D; Cardall, Christian Y.; Fuller, George M.; Cline, David

    1997-01-01

    Three-neutrino mixing schemes suggested by Cardall \\& Fuller and Acker \\& Pakvasa are compared and contrasted. Both of these schemes seek to solve the solar and atmospheric neutrino problems {\\em and} to account for the possible neutrino oscillation signal in the LSND experiment. These neutrino oscillation schemes have different atmospheric and solar neutrino signatures that will be discriminated by Super-Kamiokande and SNO. They will also have different signatures in proposed long-baseline accelerator and reactor experiments. In particular, both of these schemes would give dramatic (and dramatically different) signals in an ``intermediate baseline'' experiment, such as the proposed ICARUS detector in the Jura mountains 17 km from CERN.

  13. Solar central electric power generation - A baseline design

    Science.gov (United States)

    Powell, J. C.

    1976-01-01

    The paper presents the conceptual technical baseline design of a solar electric power plant using the central receiver concept, and derives credible cost estimates from the baseline design. The major components of the plant - heliostats, tower, receiver, tower piping, and thermal storage - are discussed in terms of technical and cost information. The assumed peak plant output is 215 MW(e), over 4000 daylight hours. The contribution of total capital investment to energy cost is estimated to be about 55 mills per kwh in mid-1974 dollars.

  14. Detecting dark energy in long baseline neutrino oscillations

    Institute of Scientific and Technical Information of China (English)

    GU Pei-Hong; BI Xiao-Jun; FENG Bo; YOUNG Bing-Lin; ZHANG Xin-Min

    2008-01-01

    In this paper, we discuss a possibility of studying properties of dark energy in long baseline neutrino oscillation experiments. We consider two types of models of neutrino dark energy. For one type of models the scalar field is taken to be quintessence-like and for the other phantom-like. In these models the scalar fields couple to the neutrinos to give rise to spatially varying neutrino masses. We will show that the two types of models predict different behaviors of the spatial variation of the neutrino masses inside the Earth and consequently result in different signals in long baseline neutrino oscillation experiments.

  15. Future long-baseline neutrino oscillations: View from Asia

    Energy Technology Data Exchange (ETDEWEB)

    Hayato, Yoshinari [Kamioka Observatory, ICRR, The University of Tokyo (Japan)

    2015-07-15

    Accelerator based long-baseline neutrino oscillation experiments have been playing important roles in revealing the nature of neutrinos. However, it turned out that the current experiments are not sufficient to study two major remaining problems, the CP violation in the lepton sector and the mass hierarchy of neutrinos. Therefore, several new experiments have been proposed. Among of them, two accelerator based long-baseline neutrino oscillation experiments, the J-PARC neutrino beam and Hyper-Kamiokande, and MOMENT, have been proposed in Asia. These two projects are reviewed in this article.

  16. Influence of baseline severity on antidepressant efficacy for anxiety disorders : meta-analysis and meta-regression

    NARCIS (Netherlands)

    de Vries, Ymkje Anna; de Jonge, Peter; van den Heuvel, Edwin; Turner, Erick H; Roest, Annelieke M

    2016-01-01

    BACKGROUND: Antidepressants are established first-line treatments for anxiety disorders, but it is not clear whether they are equally effective across the severity range. AIMS: To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalised anxiety disorder (GAD),

  17. Automated baseline change detection phase I. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    The Automated Baseline Change Detection (ABCD) project is supported by the DOE Morgantown Energy Technology Center (METC) as part of its ER&WM cross-cutting technology program in robotics. Phase 1 of the Automated Baseline Change Detection project is summarized in this topical report. The primary objective of this project is to apply robotic and optical sensor technology to the operational inspection of mixed toxic and radioactive waste stored in barrels, using Automated Baseline Change Detection (ABCD), based on image subtraction. Absolute change detection is based on detecting any visible physical changes, regardless of cause, between a current inspection image of a barrel and an archived baseline image of the same barrel. Thus, in addition to rust, the ABCD system can also detect corrosion, leaks, dents, and bulges. The ABCD approach and method rely on precise camera positioning and repositioning relative to the barrel and on feature recognition in images. In support of this primary objective, there are secondary objectives to determine DOE operational inspection requirements and DOE system fielding requirements.

  18. An Overview of the 2014 ALMA Long Baseline Campaign

    CERN Document Server

    Partnership, ALMA; Vlahakis, C; Corder, S; Remijan, A; Barkats, D; Lucas, R; Hunter, T R; Brogan, C L; Asaki, Y; Matsushita, S; Dent, W R F; Hills, R E; Phillips, N; Richards, A M S; Cox, P; Amestica, R; Broguiere, D; Cotton, W; Hales, A S; Hiriart, R; Hirota, A; Hodge, J A; Impellizzeri, C M V; Kern, J; Kneissl, R; Liuzzo, E; Marcelino, N; Marson, R; Mignano, A; Nakanishi, K; Nikolic, B; Perez, J E; Pérez, L M; Toledo, I; Aladro, R; Butler, B; Cortes, J; Cortes, P; Dhawan, V; Di Francesco, J; Espada, D; Galarza, F; Garcia-Appadoo, D; Guzman-Ramirez, L; Humphreys, E M; Jung, T; Kameno, S; Laing, R A; Leon, S; Mangum, J; Marconi, G; Nagai, H; Nyman, L -A; Perley, R; Radiszcz, M; Rodón, J A; Sawada, T; Takahashi, S; Tilanus, R P J; van Kempen, T; Vilaro, B Vila; Watson, L C; Wiklind, T; Gueth, F; Tatematsu, K; Wootten, A; Castro-Carrizo, A; Chapillon, E; Dumas, G; de Gregorio-Monsalvo, I; Francke, H; Gallardo, J; Garcia, J; Gonzalez, S; Hibbard, J E; Hill, T; Kaminski, T; Karim, A; Krips, M; Kurono, Y; Lopez, C; Martin, S; Maud, L; Morales, F; Pietu, V; Plarre, K; Schieven, G; Testi, L; Videla, L; Villard, E; Whyborn, N; Zwaan, M A; Alves, F; Andreani, P; Avison, A; Barta, M; Bedosti, F; Bendo, G J; Bertoldi, F; Bethermin, M; Biggs, A; Boissier, J; Brand, J; Burkutean, S; Casasola, V; Conway, J; Cortese, L; Dabrowski, B; Davis, T A; Trigo, M Diaz; Fontani, F; Franco-Hernandez, R; Fuller, G; Madrid, R Galvan; Giannetti, A; Ginsburg, A; Graves, S F; Hatziminaoglou, E; Hogerheijde, M; Jachym, P; Serra, I Jimenez; Karlicky, M; Klaasen, P; Kraus, M; Kunneriath, D; Lagos, C; Longmore, S; Leurini, S; Maercker, M; Magnelli, B; Vidal, I Marti; Massardi, M; Maury, A; Muehle, S; Muller, S; Muxlow, T; O'Gorman, E; Paladino, R; Petry, D; Pineda, J; Randall, S; Richer, J S; Rossetti, A; Rushton, A; Rygl, K; Monge, A Sanchez; Schaaf, R; Schilke, P; Stanke, T; Schmalzl, M; Stoehr, F; Urban, S; van Kampen, E; Vlemmings, W; Wang, K; Wild, W; Yang, Y; Iguchi, S; Hasegawa, T; Saito, M; Inatani, J; Mizuno, N; Asayama, S; Kosugi, G; Morita, K -I; Chiba, K; Kawashima, S; Okumura, S K; Ohashi, N; Ogasawara, R; Sakamoto, S; Noguchi, T; Huang, Y -D; Liu, S -Y; Kemper, F; Koch, P M; Chen, M -T; Chikada, Y; Hiramatsu, M; Iono, D; Shimojo, M; Komugi, S; Kim, J; Lyo, A -R; Muller, E; Herrera, C; Miura, R E; Ueda, J; Chibueze, J; Su, Y -N; Trejo-Cruz, A; Wang, K -S; Kiuchi, H; Ukita, N; Sugimoto, M; Kawabe, R; Hayashi, M; Miyama, S; Ho, P T P; Kaifu, N; Ishiguro, M; Beasley, A J; Bhatnagar, S; Braatz, J A; Brisbin, D G; Brunetti, N; Carilli, C; Crossley, J H; D'Addario, L; Meyer, J L Donovan; Emerson, D T; Evans, A S; Fisher, P; Golap, K; Griffith, D M; Hale, A E; Halstead, D; Hardy, E J; Hatz, M C; Holdaway, M; Indebetouw, R; Jewell, P R; Kepley, A A; Kim, D -C; Lacy, M D; Leroy, A K; Liszt, H S; Lonsdale, C J; Matthews, B; McKinnon, M; Mason, B S; Moellenbrock, G; Moullet, A; Myers, S T; Ott, J; Peck, A B; Pisano, J; Radford, S J E; Randolph, W T; Venkata, U Rao; Rawlings, M; Rosen, R; Schnee, S L; Scott, K S; Sharp, N K; Sheth, K J; Simon, R S; Tsutsumi, T; Wood, S J

    2015-01-01

    A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long...

  19. Emergency Response Capability Baseline Needs Assessment - Requirements Document

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, J A

    2016-10-04

    This document was prepared by John A. Sharry, LLNL Fire Marshal and LLNL Division Leader for Fire Protection and reviewed by LLNL Emergency Management Department Head James Colson. The document follows and expands upon the format and contents of the DOE Model Fire Protection Baseline Capabilities Assessment document contained on the DOE Fire Protection Web Site, but only addresses emergency response.

  20. Revised SRC-I project baseline. Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    1984-01-01

    The SRC Process Area Design Baseline consists of six volumes. The first four were submitted to DOE on 9 September 1981. The fifth volume, summarizing the Category A Engineering Change Proposals (ECPs), was not submitted. The sixth volume, containing proprietary information on Kerr-McGee's Critical Solvent Deashing System, was forwarded to BRHG Synthetic Fuels, Inc. for custody, according to past instructions from DOE, and is available for perusal by authorized DOE representatives. DOE formally accepted the Design Baseline under ICRC Release ECP 4-1001, at the Project Configuration Control Board meeting in Oak Ridge, Tennessee on 5 November 1981. The documentation was then revised by Catalytic, Inc. to incorporate the Category B and C and Post-Baseline Engineering Change Proposals. Volumes I through V of the Revised Design Baseline, dated 22 October 1982, are nonproprietary and they were issued to the DOE via Engineering Change Notice (ECN) 4-1 on 23 February 1983. Volume VI again contains proprieary information on Kerr-McGee Critical Solvent Deashing System; it was issued to Burns and Roe Synthetic Fuels, Inc. Subsequently, updated process descriptions, utility summaries, and errata sheets were issued to the DOE and Burns and Roe Synthetic Fuels, Inc. on nonproprietary Engineering Change Notices 4-2 and 4-3 on 24 May 1983.

  1. Attendance at Health Promotion Programs: Baseline Predictors and Program Outcomes.

    Science.gov (United States)

    Atkins, Catherine J.; And Others

    1990-01-01

    As part of a family cardiovascular health promotion project, 111 Mexican-American and 95 Anglo-American families with fifth or sixth grade children were assigned to either a primary prevention program involving 18 sessions or to a control condition. Correlates of attendance were low baseline scores on physical activity and cardiovascular fitness…

  2. ECG baseline wander reduction using linear phase filters

    NARCIS (Netherlands)

    Alsté, van J.A.; Eck, van W.; Hermann, O.E.

    1986-01-01

    The continuous real time reduction of baseline wander is a considerable problem in electrocardiography during exercises. Our solution consists of spectral filtering. The legitimacy of high-pass filtering of the ECG by means of digital linear phase filters with a low cut-off frequency as high as the

  3. Moon-Based INSAR Geolocation and Baseline Analysis

    Science.gov (United States)

    Liu, Guang; Ren, Yuanzhen; Ye, Hanlin; Guo, Huadong; Ding, Yixing; Ruan, Zhixing; Lv, Mingyang; Dou, Changyong; Chen, Zhaoning

    2016-07-01

    Earth observation platform is a host, the characteristics of the platform in some extent determines the ability for earth observation. Currently most developing platforms are satellite, in contrast carry out systematic observations with moon based Earth observation platform is still a new concept. The Moon is Earth's only natural satellite and is the only one which human has reached, it will give people different perspectives when observe the earth with sensors from the moon. Moon-based InSAR (SAR Interferometry), one of the important earth observation technology, has all-day, all-weather observation ability, but its uniqueness is still a need for analysis. This article will discuss key issues of geometric positioning and baseline parameters of moon-based InSAR. Based on the ephemeris data, the position, liberation and attitude of earth and moon will be obtained, and the position of the moon-base SAR sensor can be obtained by coordinate transformation from fixed seleno-centric coordinate systems to terrestrial coordinate systems, together with the Distance-Doppler equation, the positioning model will be analyzed; after establish of moon-based InSAR baseline equation, the different baseline error will be analyzed, the influence of the moon-based InSAR baseline to earth observation application will be obtained.

  4. BASELINE DESIGN/ECONOMICS FOR ADVANCED FISCHER-TROPSCH TECHNOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    None

    1998-04-01

    Bechtel, along with Amoco as the main subcontractor, developed a Baseline design, two alternative designs, and computer process simulation models for indirect coal liquefaction based on advanced Fischer-Tropsch (F-T) technology for the U. S. Department of Energy's (DOE's) Federal Energy Technology Center (FETC).

  5. Baseline design of an OTEC pilot plantship. Volume C. Specifications

    Energy Technology Data Exchange (ETDEWEB)

    Glosten, L. R.; Bringloe, Thomas; Soracco, Dave; Fenstermacher, Earl; Magura, Donald; Sander, Olof; Richards, Dennis; Seward, Jerry

    1979-05-01

    Volume C is part of a three-volume report that presents a baseline engineering design of an Ocean Thermal Energy Conversion (OTEC) plantship. This volume provides the specifications for the hull, cold-water pipe, ship outfitting and machinery, OTEC power system, electrical system, and folded-tube heat exchangers.

  6. Delta Healthy Sprouts: Participants' Diet and Food Environment at Baseline

    Science.gov (United States)

    Local food environments influence the nutrition and health of area residents. This baseline analysis focuses on the food environments of women who participated in the Delta Healthy Sprouts project, a randomized, controlled, comparative trial designed to test the efficacy of two Maternal, Infant, an...

  7. The Dutch CAFE baseline: In or out of line?

    NARCIS (Netherlands)

    Jimmink BA; Folkert RJM; Thomas R; Beck JP; Eerdt MM van; Elzenga HE; Hoek KW van der; Hoen A; Peek CJ; LED; KMD; NMD; LVM; RIM; LDL

    2004-01-01

    The European Commission is constructing a strategy on air pollution within the Clean Air For Europe (CAFE) programme. This strategy will be based on assessments using the RAINS model for different policy ambitions where the CAFE baseline scenario and control strategies are employed. The Netherlands

  8. IEA Wind Task 26: Offshore Wind Farm Baseline Documentation

    Energy Technology Data Exchange (ETDEWEB)

    Smart, Gavin [Offshore Renewable Energy Catapult, Blyth, Northumberland (United Kingdom); Smith, Aaron [National Renewable Energy Lab. (NREL), Golden, CO (United States); Warner, Ethan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sperstad, Iver Bakken [SINTEF Energy Research, Trondheim (Norway); Prinsen, Bob [Ecofys, Utrecht (Netherlands). TKI Wind Op Zee; Lacal-Arantegui, Roberto [European Commission Joint Research Centre (JRC), Brussels (Belgium)

    2016-06-02

    This document has been produced to provide the definition and rationale for the Baseline Offshore Wind Farm established within IEA Wind Task 26--Cost of Wind Energy. The Baseline has been developed to provide a common starting point for country comparisons and sensitivity analysis on key offshore wind cost and value drivers. The baseline project reflects an approximate average of the characteristics of projects installed between 2012 and 2014, with the project life assumed to be 20 years. The baseline wind farm is located 40 kilometres (km) from construction and operations and maintenance (O&M) ports and from export cable landfall. The wind farm consists of 100 4-megawatt (MW) wind turbines mounted on monopile foundations in an average water depth of 25 metres (m), connected by 33-kilovolt (kV) inter-array cables. The arrays are connected to a single offshore substation (33kV/220kV) mounted on a jacket foundation, with the substation connected via a single 220kV export cable to an onshore substation, 10km from landfall. The wind farm employs a port-based O&M strategy using crew-transfer vessels.

  9. Baseline Gas Turbine Development Program. Eleventh quarterly progress report

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, F.W.; Wagner, C.E.

    1975-07-31

    Progress is reported for a program to demonstrate by 1976 an experimental gas turbine powered automobile which meets the 1978 Federal Emissions Standards, has significantly improved fuel economy, and is competitive in performance, reliability, and potential manufacturing cost with the conventional piston engine powered, standard size American automobile. NASA completed initial heat balance testing of a baseline engine. An additional 450 hours were run on ceramic regenerators and seals. Seal wear rates are very good, and the elastomeric mounting system was satisfactory. An engine/control oil supply system based on the power steering pump is successfully operating in baseline vehicles. The design of the upgraded engine power turbine nozzle actuator was finalized, and layouts of the inlet guide vane actuator are in process. A lock-up torque converter was installed in the free rotor vehicle. Baseline engine and vehicle testing of water injection and variable inlet guide vanes was completed. A thermal analysis of the gas generator is in process. A steady-state, full power analysis was made. A three-dimensional stress analysis of the compressor cover was made. The power turbine nozzle actuating system layout was completed. The analytical studies of the power turbine rotor bearings were completed. MTI completed the design of the gas generator rotor simulation fixture and is starting to build it. Optimized reduction gears were successfully tested in a baseline engine.

  10. Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana

    Directory of Open Access Journals (Sweden)

    Abuaku Benjamin

    2012-11-01

    Full Text Available Abstract Background In 2008, artemether - lumefantrine (AL and dihydroartemisinin - piperaquine (DHAP were added to artesunate - amodiaquine (AS-AQ as first-line drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country. Methods The study was a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based 20/120 mg AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with fever. Results A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5% (95% CI: 92.1, 98.6 and 95.4% (95% CI: 90.3, 98.0, respectively, with statistically significant differences between the ecological zones. The 90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4 was significantly the lowest compared with 100% (95% CI: 93.2, 99.9 in the forest zone and 93.8% (95% CI: 77.8, 98.9 in the coastal zone (P = 0.017. Fever and parasite clearance were slower among children enrolled in the savannah zone. Gametocytaemia after day-3 post-treatment was rare in all the zones. Conclusions The study has shown that AL remains efficacious in Ghana with

  11. Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study

    Directory of Open Access Journals (Sweden)

    Vaughan-Williams Charles H

    2012-12-01

    Full Text Available Abstract Background Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. Methods An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR. Following diagnosis, patients were treated with artemether-lumefantrine (Coartem® and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. Results Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1 gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N. Ten of the 16 samples carried the wild type haplotype (CVMNK at codons 72-76 of the chloroquine resistance transporter gene (pfcrt; three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. Conclusions The absence of mdr1 gene copy number variation detected in this study

  12. Effect of water deprivation on baseline and stress-induced corticosterone levels in the Children's python (Antaresia childreni).

    Science.gov (United States)

    Dupoué, Andréaz; Angelier, Frédéric; Lourdais, Olivier; Bonnet, Xavier; Brischoux, François

    2014-02-01

    Corticosterone (CORT) secretion is influenced by endogenous factors (e.g., physiological status) and environmental stressors (e.g., ambient temperature). Heretofore, the impact of water deprivation on CORT plasma levels has not been thoroughly investigated. However, both baseline CORT and stress-induced CORT are expected to respond to water deprivation not only because of hydric stress per se, but also because CORT is an important mineralocorticoid in vertebrates. We assessed the effects of water deprivation on baseline CORT and stress-induced CORT, in Children's pythons (Antaresia childreni), a species that experiences seasonal droughts in natural conditions. We imposed a 52-day water deprivation on a group of unfed Children's pythons (i.e., water-deprived treatment) and provided water ad libitum to another group (i.e., control treatment). We examined body mass variations throughout the experiment, and baseline CORT and stress-induced CORT at the end of the treatments. Relative body mass loss averaged ~10% in pythons without water, a value 2 to 4 times higher compared to control snakes. Following re-exposition to water, pythons from the water-deprived treatment drank readily and abundantly and attained a body mass similar to pythons from the control treatment. Together, these results suggest a substantial dehydration as a consequence of water deprivation. Interestingly, stress-induced but not baseline CORT level was significantly higher in water-deprived snakes, suggesting that baseline CORT might not respond to this degree of dehydration. Therefore, possible mineralocorticoid role of CORT needs to be clarified in snakes. Because dehydration usually induces adjustments (reduced movements, lowered body temperature) to limit water loss, and decreases locomotor performances, elevated stress-induced CORT in water-deprived snakes might therefore compensate for altered locomotor performances. Future studies should test this hypothesis.

  13. Impact of baseline characteristics on outcomes of carotid artery stenting in acute ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Yu CS

    2016-03-01

    Full Text Available Cheng-Sheng Yu,1,* Chih-Ming Lin,2,3,* Chi-Kuang Liu,4 Henry Horng-Shing Lu1 1Institute of Statistics and Big Data Research Center, National Chiao Tung University, Hsinchu, 2Stroke Centre and Department of Neurology, Chunghua Christian Hospital, Chunghua, 3Graduate Institute of Biological Science and Technology, National Chiao Tung University, Hsinchu, 4Department of Medical Imaging, Chunghua Christian Hospital, Chunghua, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Carotid artery stenting is an effective treatment for ischemic stroke patients with moderate-to-severe carotid artery stenosis. However, the midterm outcome for patients undergoing this procedure varies considerably with baseline characteristics. To determine the impact of baseline characteristics on outcomes following carotid artery stenting, data from 107 eligible patients with a first episode of ischemic stroke were collected by retrospective chart review. A modified Rankin Scale (mRS was used to divide patients into two baseline groups, mRS ≤2 and mRS >2. A three-step decision-tree statistical analysis was conducted. After weighting the decision-tree parameters, the following impact hierarchy was obtained: admission low-density lipoprotein, gouty arthritis, chronic kidney disease, ipsilateral common carotid artery resistance index, contralateral ophthalmic artery resistance index, sex, and dyslipidemia. The finite-state machine model demonstrated that, in patients with baseline mRS ≤2, 46% had an improved mRS score at follow-up, whereas 54% had a stable mRS score. In patients with baseline mRS >2, a stable mRS score was observed in 75%, improved score in 23%, and a poorer score in 2%. Admission low-density lipoprotein was the strongest predictive factor influencing poststenting outcome. In addition, our study provides further evidence that carotid artery stenting can be of benefit in first-time ischemic stroke patients with baseline m

  14. ALMA Long Baseline Campaigns: Phase Characteristics of Atmosphere at Long Baselines in the Millimeter and Submillimeter Wavelengths

    Science.gov (United States)

    Matsushita, Satoki; Asaki, Yoshiharu; Fomalont, Edward B.; Morita, Koh-Ichiro; Barkats, Denis; Hills, Richard E.; Kawabe, Ryohei; Maud, Luke T.; Nikolic, Bojan; Tilanus, Remo P. J.; Vlahakis, Catherine; Whyborn, Nicholas D.

    2017-03-01

    We present millimeter- and submillimeter-wave phase characteristics measured between 2012 and 2014 of Atacama Large Millimeter/submillimeter Array long baseline campaigns. This paper presents the first detailed investigation of the characteristics of phase fluctuation and phase correction methods obtained with baseline lengths up to ∼15 km. The basic phase fluctuation characteristics can be expressed with the spatial structure function (SSF). Most of the SSFs show that the phase fluctuation increases as a function of baseline length, with a power-law slope of ∼0.6. In many cases, we find that the slope becomes shallower (average of ∼0.2–0.3) at baseline lengths longer than ∼1 km, namely showing a turn-over in SSF. These power law slopes do not change with the amount of precipitable water vapor (PWV), but the fitted constants have a weak correlation with PWV, so that the phase fluctuation at a baseline length of 10 km also increases as a function of PWV. The phase correction method using water vapor radiometers (WVRs) works well, especially for the cases where PWV > 1 {mm}, which reduces the degree of phase fluctuations by a factor of two in many cases. However, phase fluctuations still remain after the WVR phase correction, suggesting the existence of other turbulent constituent that cause the phase fluctuation. This is supported by occasional SSFs that do not exhibit any turn-over; these are only seen when the PWV is low (i.e., when the WVR phase correction works less effectively) or after WVR phase correction. This means that the phase fluctuation caused by this turbulent constituent is inherently smaller than that caused by water vapor. Since in these rare cases there is no turn-over in the SSF up to the maximum baseline length of ∼15 km, this turbulent constituent must have scale height of 10 km or more, and thus cannot be water vapor, whose scale height is around 1 km. Based on the characteristics, this large scale height turbulent constituent is

  15. Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI.

    Science.gov (United States)

    Marques, Inês Brás; Matias, Fernando; Silva, Eduardo Duarte; Cunha, Luis; Sousa, Lívia

    2014-04-01

    When assessing and managing a patient with optic neuritis (ON), the risk of future development of multiple sclerosis (MS) is an important issue, as this can be the first presentation of the disease. Although the presence of lesions on baseline brain MRI is the strongest predictor of MS conversion, some patients with normal imaging also develop MS. We aimed to estimate MS risk in patients with ON and a normal baseline MRI and identify individuals with higher risk of conversion. We performed a retrospective study including patients with idiopathic ON and normal baseline brain MRI who presented to our hospital over an 8 year period. Of a total of 42 patients, 10 converted to MS: five during the first follow-up year, seven during the first 2 years and all of the patients within the first 5 years, with a 5 year MS conversion rate of 23.8%. MS conversion rates were significantly higher in patients with history of previous symptoms suggestive of demyelination (p=0.002), cerebrospinal fluid oligoclonal bands unmatched in serum (p=0.004) and incomplete visual acuity recovery (≤6/12) after 1 year (p=0.002). Lower conversion rates were found in patients with optic disc edema (p=0.022). According to these results, a significant proportion of patients with idiopathic ON and a normal baseline brain MRI will develop MS, with a higher risk during the first 5 years. Therefore, in the presence of factors in favor of MS conversion, close follow-up, including semestral medical consultations and yearly brain MRI, can be recommended. Early immunomodulatory treatment may be individually considered as it can delay conversion and reduce new lesion development rate.

  16. Baseline characteristics influencing quality of life in women undergoing gynecologic oncology surgery

    Directory of Open Access Journals (Sweden)

    Jenison Eric L

    2007-05-01

    Full Text Available Abstract Background Quality of life (QoL measurements are important in evaluating cancer treatment outcomes. Factors other than cancer and its treatment may have significant effects on QoL and affect assessment of treatments. Baseline data from longitudinal studies of women with endometrial or ovarian cancer or adnexal mass determined at surgery to be benign were analyzed to determine the degree to which QoL is affected by baseline differences in demographic variables and health. Methods This study examined the effect of independent variables on domains of the Functional Assessment of Cancer Therapy (FACT-G pre-operatively in gynecologic oncology patients undergoing surgery for pelvic mass suspected to be malignant or endometrial cancer. Patients also completed the Short Form Medical Outcomes Survey (SF-36 questionnaire (a generic health questionnaire that measures physical and mental health. Independent variables were surgical diagnosis (ovarian or endometrial cancer, benign mass, age, body mass index (BMI, educational level, marital status, smoking status, physical (PCS and mental (MCS summary scores of the SF-36. Multiple regression analysis was used to determine the influence of these variables on FACT-G domain scores (physical, functional, social and emotional well-being. Results Data were collected on 157 women at their pre-operative visit (33 ovarian cancer, 45 endometrial cancer, 79 determined at surgery to be benign. Mean scores on the FACT-G subscales and SF-36 summary scores did not differ as a function of surgical diagnosis. PCS, MCS, age, and educational level were positively correlated with physical well-being, while increasing BMI was negatively correlated. Functional well-being was positively correlated with PCS and MCS and negatively correlated with BMI. Social well-being was positively correlated with MCS and negatively correlated with BMI and educational level. PCS, MCS and age were positively correlated with emotional well

  17. Neoadjuvant chemoradiotherapy of rectal carcinoma. Baseline hematologic parameters influencing outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Hodek, Miroslav; Sirak, Igor; Paluska, Petr; Kopecky, Jindrich; Petera, Jiri; Vosmik, Milan [University Hospital in Hradec Kralove, Department of Oncology and Radiotherapy, Hradec Kralove (Czech Republic); Ferko, Alexander; Oerhalmi, Julius [University Hospital in Hradec Kralove, Department of Surgery, Hradec Kralove (Czech Republic); Hovorkova, Eva; Hadzi Nikolov, Dimitar [University Hospital in Hradec Kralove, Fingerland Department of Pathology, Hradec Kralove (Czech Republic)

    2016-09-15

    The link between the blood count and a systemic inflammatory response (SIR) is indisputable and well described. Pretreatment hematological parameters may predict the overall clinical outcomes in many types of cancer. Thus, this study aims to systematically evaluate the relationship between baseline blood count levels and treatment response in rectal cancer patients treated with neoadjuvant chemoradiotherapy. From 2009-2015, 173 patients with locally advanced rectal cancer were retrospectively enrolled in the study and analyzed. The baseline blood count was recorded in all patients 1 week before chemoradiation. Tumor response was evaluated through pathologic findings. Blood count levels which included RBC (red blood cells), Hb (hemoglobin), PLT (platelet count), neutrophil count, WBC (white blood cells), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) were analyzed in relation to tumor downstaging, pCR (pathologic complete response), OS (overall survival), and DFS (disease-free survival). Hb levels were associated with a response in logistic regression analysis: pCR (p = 0.05; OR 1.04, 95 % CI 1.00-1.07); T downstaging (p = 0.006; OR 1.03, 95 % CI 1.01-1.05); N downstaging (p = 0.09; OR 1.02, 95 % CI 1.00-1.04); T or N downstaging (p = 0.007; OR 1.04, 95 % CI 1.01-1.07); T and N downstaging (p = 0.02; OR 1.02, 95 % CI 1.00-1.04); Hb and RBC were the most significant parameters influencing OS; PLT was a negative prognostic factor for OS and DFS (p = 0.008 for OS); an NLR value of 2.8 was associated with the greatest significance for OS (p = 0.03) and primary tumor downstaging (p = 0.02). Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma. (orig.) [German] Die Verbindung zwischen dem Blutbild und der systemischen Entzuendungsreaktion (''systemic inflammatory response'', SIR) ist unbestreitbar und gut beschrieben. Aufgrund der

  18. Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

    Science.gov (United States)

    Beaton, K. H.; Bloomberg, J. J.

    2016-01-01

    One of the greatest challenges for sensorimotor adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. This information could guide individually customized countermeasures, which would enable more efficient use of crew time and provide better outcomes. The principal aim of this work is to look for baseline performance metrics that relate to locomotor adaptability. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations ("noise") in motor performance, as a predictor of individual adaptive capabilities.

  19. Forecasting Sensorimotor Adaptability from Baseline Inter­-Trial Correlations

    Science.gov (United States)

    Beaton, Kara H.; Bloomberg, Jacob J.

    2016-01-01

    One of the greatest challenges for sensorimotor adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a one-size-fits-all approach is inappropriate. Therefore it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. This information could guide individually customized countermeasures, which would enable more efficient use of crew time and provide better outcomes. The principal aim of this work is to look for baseline performance metrics that relate to locomotor adaptability. To-date, a strong relationship has been found between baseline inter-trial correlations, the trial-to-trial fluctuations ("noise") in motor performance, and adaptability in two oculomotor systems (see Preliminary Results). We now propose an analogous predictive mechanisms in the locomotor system.

  20. Statistical Mechanics of Node-perturbation Learning with Noisy Baseline

    Science.gov (United States)

    Hara, Kazuyuki; Katahira, Kentaro; Okada, Masato

    2017-02-01

    Node-perturbation learning is a type of statistical gradient descent algorithm that can be applied to problems where the objective function is not explicitly formulated, including reinforcement learning. It estimates the gradient of an objective function by using the change in the object function in response to the perturbation. The value of the objective function for an unperturbed output is called a baseline. Cho et al. proposed node-perturbation learning with a noisy baseline. In this paper, we report on building the statistical mechanics of Cho's model and on deriving coupled differential equations of order parameters that depict learning dynamics. We also show how to derive the generalization error by solving the differential equations of order parameters. On the basis of the results, we show that Cho's results are also apply in general cases and show some general performances of Cho's model.

  1. Implementing wide baseline matching algorithms on a graphics processing unit.

    Energy Technology Data Exchange (ETDEWEB)

    Rothganger, Fredrick H.; Larson, Kurt W.; Gonzales, Antonio Ignacio; Myers, Daniel S.

    2007-10-01

    Wide baseline matching is the state of the art for object recognition and image registration problems in computer vision. Though effective, the computational expense of these algorithms limits their application to many real-world problems. The performance of wide baseline matching algorithms may be improved by using a graphical processing unit as a fast multithreaded co-processor. In this paper, we present an implementation of the difference of Gaussian feature extractor, based on the CUDA system of GPU programming developed by NVIDIA, and implemented on their hardware. For a 2000x2000 pixel image, the GPU-based method executes nearly thirteen times faster than a comparable CPU-based method, with no significant loss of accuracy.

  2. Configurations of the Long-Baseline Neutrino Experiment

    CERN Document Server

    Barger, Vernon; Chatterjee, Animesh; Gandhi, Raj; Marfatia, Danny; Masud, Mehedi

    2014-01-01

    We perform a comprehensive study of the ability of the Long-Baseline Neutrino Experiment (LBNE) to answer outstanding questions in the neutrino sector. We consider the sensitivities to the mass hierarchy, the octant of $\\theta_{23}$ and to CP violation using data from beam and atmospheric neutrinos. We evaluate the dependencies on the precision with which $\\theta_{13}$ will be measured by reactor experiments, on the detector size, beam power and exposure time, on detector magnetization, and on the systematic uncertainties achievable with and without a near detector. We find that a 35 kt LBNE with a near detector will resolve the eight-fold degeneracy that is intrinsic to long baseline experiments and will meet the primary goals of oscillation physics that it is designed for.

  3. Long-Baseline Neutrino Physics in the U.S

    Energy Technology Data Exchange (ETDEWEB)

    Kopp, Sacha E. [Department of Physics, University of Texas at Austin, 1 University Station C1600, Austin, Texas 78712 (United States)

    2007-06-15

    Long-baseline neutrino oscillation physics in the U.S. is centered at the Fermi National Accelerator Laboratory (FNAL), in particular at the Neutrinos at the Main Injector (NuMI) beamline commissioned in 2004-2005. Already, the MINOS experiment has published its first results confirming the disappearance of {nu}{sub {mu}}'s across a 735 km baseline. The forthcoming NO{nu}A experiment will search for the transition {nu}{sub {mu}}{yields}{nu}{sub e} and use this transition to understand the mass heirarchy of neutrinos. These, as well as other conceptual ideas for future experiments using the NuMI beam, will be discussed. The turn-on of the NuMI facility has been positive, with over 310 kW beam power achieved. Plans for increasing the beam intensity once the Main Injector accelerator is fully-dedicated to the neutrino program will be presented.

  4. Baseline ecological risk assessment Salmon Site, Lamar County, Mississippi

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-04-01

    The Salmon Site (SS), formerly the Tatum Dome Test Site, located in Mississippi was the site of two nuclear and two gas explosion tests conducted between 1964 and 1970. A consequence of these testing activities is that radionuclides were released into the salt dome, where they are presently contained. During reentry drilling and other site activities, incidental liquid and solid wastes that contained radioactivity were generated, resulting in some soil, ground water and equipment contamination. As part of the remedial investigation effort, a Baseline Ecological Risk Assessment was conducted at the SS. The purpose is to gauge ecological and other environmental impacts attributable to past activities at the former test facility. The results of this facility-specific baseline risk assessment are presented in this document.

  5. Coral reef baselines: how much macroalgae is natural?

    Science.gov (United States)

    Bruno, John F; Precht, William F; Vroom, Peter S; Aronson, Richard B

    2014-03-15

    Identifying the baseline or natural state of an ecosystem is a critical step in effective conservation and restoration. Like most marine ecosystems, coral reefs are being degraded by human activities: corals and fish have declined in abundance and seaweeds, or macroalgae, have become more prevalent. The challenge for resource managers is to reverse these trends, but by how much? Based on surveys of Caribbean reefs in the 1970s, some reef scientists believe that the average cover of seaweed was very low in the natural state: perhaps less than 3%. On the other hand, evidence from remote Pacific reefs, ecological theory, and impacts of over-harvesting in other systems all suggest that, historically, macroalgal biomass may have been higher than assumed. Uncertainties about the natural state of coral reefs illustrate the difficulty of determining the baseline condition of even well studied systems.

  6. Measurement of baseline and orientation between distributed aerospace platforms.

    Science.gov (United States)

    Wang, Wen-Qin

    2013-01-01

    Distributed platforms play an important role in aerospace remote sensing, radar navigation, and wireless communication applications. However, besides the requirement of high accurate time and frequency synchronization for coherent signal processing, the baseline between the transmitting platform and receiving platform and the orientation of platform towards each other during data recording must be measured in real time. In this paper, we propose an improved pulsed duplex microwave ranging approach, which allows determining the spatial baseline and orientation between distributed aerospace platforms by the proposed high-precision time-interval estimation method. This approach is novel in the sense that it cancels the effect of oscillator frequency synchronization errors due to separate oscillators that are used in the platforms. Several performance specifications are also discussed. The effectiveness of the approach is verified by simulation results.

  7. Fissile materials disposition program plutonium immobilization project baseline formulation

    Energy Technology Data Exchange (ETDEWEB)

    Ebbinghaus, B B; Armantrout, G A; Gray, L; Herman, C C; Shaw, H F; Van Konynenburg, R A

    2000-09-01

    Since 1994 Lawrence Livermore National Laboratory (LLNL), with the help of several other laboratories and university groups, has been the lead laboratory for the Plutonium Immobilization Project (PIP). This involves, among other tasks, the development of a formulation and a fabrication process for a ceramic to be used in the immobilization of excess weapons-usable plutonium. This report reviews the history of the project as it relates to the development of the ceramic form. It describes the sample test plan for the pyrochlore-rich ceramic formulation that was selected, and it specifies the baseline formulation that has been adopted. It also presents compositional specifications (e.g. precursor compositions and mixing recipes) and other form and process specifications that are linked or potentially linked to the baseline formulation.

  8. The Fermilab Short-Baseline Program: MicroBooNE

    Energy Technology Data Exchange (ETDEWEB)

    Schukraft, Anne [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2016-01-01

    The MicroBooNE experiment is the first of three detectors of the Fermilab short-baseline neutrino program that started operation in the Booster Neutrino Beamline in October 2015 [1]. When completed, the three-detector lineup will explore short-baseline neutrino oscillations and will be sensitive to sterile neutrino scenarios. MicroBooNE in itself is now starting its own physics program, with the measurement of neutrino-argon cross sections in the ~1GeV range being one of its main physics goals. These proceedings describe the status of the detector, the start of operation, and the automated reconstruction of the first neutrino events observed with MicroBooNE. Prospects for upcoming cross section measurements are also given.

  9. Degeneracies in long-baseline neutrino experiments from nonstandard interactions

    CERN Document Server

    Liao, Jiajun; Whisnant, Kerry

    2016-01-01

    We study parameter degeneracies that can occur in long-baseline neutrino appearance experiments due to nonstandard interactions (NSI). For a single off-diagonal NSI parameter, and neutrino and antineutrino measurements at a single L/E, there exists a continuous four-fold degeneracy (related to the mass hierarchy and $\\theta_{23}$ octant) that renders the mass hierarchy, octant, and CP phase unknowable. Even with a combination of NO$\

  10. Baseline Gas Turbine Development Program. Fourteenth quarterly progress report

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, F W; Wagner, C E

    1976-04-30

    Progress is reported for a Baseline Gas Turbine Development Program sponsored by the Heat Engine Systems Branch, Division of Transportation Energy Conservation (TEC) of the Energy Research and Development Administration (ERDA). Structurally, this program is made up of three parts: (1) documentation of the existing automotive gas turbine state-of-the-art; (2) conduction of an extensive component improvement program; and (3) utilization of the improvements in the design, and building of an Upgraded Engine capable of demonstrating program goals.

  11. Tools for NEPA compliance: Baseline reports and compliance guides

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, T.A. [Sandia National Labs., Albuquerque, NM (United States); Hansen, R.P. [Hansen Environmental Consultants, Englewood, CO (United States)

    1994-12-31

    Environmental baseline documents and NEPA compliance guides should be carried in every NEPA implementation ``tool kit``. These two indispensable tools can play a major role in avoiding repeated violations of NEPA requirements that have occurred over the past 26 years. This paper describes these tools, discusses their contents, and explains how they are used to prepare better NEPA documents more cost-effectively. Focus is on experience at Sandia Laboratories (NM).

  12. Logistics Operations Management Center: Maintenance Support Baseline (LOMC-MSB)

    Science.gov (United States)

    Kurrus, R.; Stump, F.

    1995-01-01

    The Logistics Operations Management Center Maintenance Support Baseline is defined. A historical record of systems, applied to and deleted from, designs in support of future management and/or technical analysis is provided. All Flight elements, Ground Support Equipment, Facility Systems and Equipment and Test Support Equipment for which LOMC has responsibilities at Kennedy Space Center and other locations are listed. International Space Station Alpha Program documentation is supplemented. The responsibility of the Space Station Launch Site Support Office is established.

  13. GPS dynamic cycle slip detection and correction with baseline constraint

    Institute of Scientific and Technical Information of China (English)

    Liu Zhenkun; Huang Ahunji

    2009-01-01

    When the cycle slips take place in the attitude determination of a moving platform, the precision of the attitude will be impaired badly. A method of cycle slip detection and correction is proposed, which is suitable to the dynamic measurement using GPS carrier phase: the cycle slips detection is first achieved by triple difference observables, then the cycle slips correction is performed with baseline length constraint. The simulation results show that the proposed method is effective to the dynamic cycle slips problem.

  14. Linking solar and long baseline terrestrial neutrino experiments.

    Science.gov (United States)

    Akhmedov, E K; Branco, G C; Rebelo, M N

    2000-04-17

    We show that, in the framework of three light neutrino species with hierarchical masses and assuming no fine tuning between the entries of the neutrino mass matrix, one can use the solar neutrino data to obtain information on the element U(e3) of the lepton mixing matrix. Conversely, a measurement of U(e3) in atmospheric or long baseline accelerator or reactor neutrino experiments would help discriminate between possible oscillation solutions of the solar neutrino problem.

  15. Re-Creating Missing Population Baselines for Pacific Reef Sharks

    OpenAIRE

    Marc O Nadon; Julia K. Baum; Ivor D Williams; Mcpherson, Jana M; Zgliczynski, Brian J.; Richards, Benjamin L.; Schroeder, Robert E.; Russell E Brainard

    2012-01-01

    Summary Abstract Sharks and other large predators are scarce on most coral reefs, but studies of their historical ecology provide qualitative evidence that predators were once numerous in these ecosystems. Quantifying density of sharks in the absence of humans (baseline) is, however, hindered by a paucity of pertinent time-series data. Recently researchers have used underwater visual surveys, primarily of limited spatial extent or nonstandard design, to infer negative associations between ree...

  16. Challenges of collecting baseline data in emergency settings

    Directory of Open Access Journals (Sweden)

    Jennifer Schlecht

    2007-12-01

    Full Text Available Although the humanitarian community acknowledgesthe need for good quality data in programme design andmonitoring, the challenges and demands of field settingshave too often led to the argument that “we just don’thave time” or “it is too difficult”. Yet without the allocationof time and resources to the collection of baseline andmonitoring data, project activities cannot be groundedin strong evidence from programme evaluation.

  17. Integrated Baseline System (IBS) Version 2.0: User guide

    Energy Technology Data Exchange (ETDEWEB)

    Bower, J.C. [Bower Software Services, Kennewick, WA (United States); Burford, M.J.; Downing, T.R.; Matsumoto, S.W.; Schrank, E.E.; Williams, J.R.; Winters, C.; Wood, B.M.

    1994-03-01

    The Integrated Baseline System (IBS) is an emergency management planning and analysis tool being developed under the direction of the Federal Emergency Management Agency. This User Guide explains how to start and use the IBS Program, which is designed to help civilian emergency management personnel to plan for and support their responses to a chemical-releasing event at a military chemical stockpile. The intended audience for this document is all users of the IBS, especially emergency management planners and analysts.

  18. Optimized Two-Baseline Beta-Beam Experiment

    CERN Document Server

    Choubey, Sandhya; Donini, Andrea; Fernandez-Martinez, Enrique

    2009-01-01

    We propose a realistic Beta-Beam experiment with four source ions and two baselines for the best possible sensitivity to theta_{13}, CP violation and mass hierarchy. Neutrinos from 18Ne and 6He with Lorentz boost gamma=350 are detected in a 500 kton water Cerenkov detector at a distance L=650 km (first oscillation peak) from the source. Neutrinos from 8B and 8Li are detected in a 50 kton magnetized iron detector at a distance L=7000 km (magic baseline) from the source. Since the decay ring requires a tilt angle of 34.5 degrees to send the beam to the magic baseline, the far end of the ring has a maximum depth of d=2132 m for magnetic field strength of 8.3 T, if one demands that the fraction of ions that decay along the straight sections of the racetrack geometry decay ring (called livetime) is 0.3. We alleviate this problem by proposing to trade reduction of the livetime of the decay ring with the increase in the boost factor of the ions, such that the number of events at the detector remains almost the same....

  19. Gravity sensing with Very Long Baseline Atom Interferometry

    Science.gov (United States)

    Schlippert, Dennis; Albers, Henning; Richardson, Logan L.; Nath, Dipankar; Meiners, Christian; Wodey, Etienne; Schubert, Christian; Ertmer, Wolfgang; Rasel, Ernst M.

    2016-05-01

    Very Long Baseline Atom Interferometry (VLBAI) has applications in high-accuracy absolute gravimetry, gravity-gradiometry, and for tests of fundamental physics. Extending the baseline of atomic gravimeters from tens of centimeters to meters opens the route towards competition with superconducting gravimeters. The VLBAI-test stand will consist of a 10m-baseline atom interferometer allowing for free fall times of seconds. In order to suppress environmental noise, the facility utilizes a state-of-the-art vibration isolation platform and a three-layer magnetic shield. We envisage a resolution of local gravitational acceleration of 5 .10-10 m/ s2 with sub-ppb inaccuracy. Operation as a gradiometer will allow to resolve the gravity gradient at a resolution of 5 .10-10 1/ s2. The operation of VLBAI as a differential dual-species gravimeter using ultracold mixtures of Yb and Rb atoms enables quantum tests of the universality of free fall (UFF) at an unprecedented level, with the potential to surpass the accuracy of the best experiments to date. We report on a quantum test of the UFF using two different chemical elements, 39 K and 87 Rb, reaching a 100 ppb inaccuracy and show the potential of UFF tests in VLBAI at an inaccuracy of 10-13 and beyond.

  20. COMSATCOM service technical baseline strategy development approach using PPBW concept

    Science.gov (United States)

    Nguyen, Tien M.; Guillen, Andy T.

    2016-05-01

    This paper presents an innovative approach to develop a Commercial Satellite Communications (COMSATCOM) service Technical Baseline (TB) and associated Program Baseline (PB) strategy using Portable Pool Bandwidth (PPBW) concept. The concept involves trading of the purchased commercial transponders' Bandwidths (BWs) with existing commercial satellites' bandwidths participated in a "designated pool bandwidth"3 according to agreed terms and conditions. Space Missile Systems Center (SMC) has been implementing the Better Buying Power (BBP 3.0) directive4 and recommending the System Program Offices (SPO) to own the Program and Technical Baseline (PTB) [1, 2] for the development of flexible acquisition strategy and achieving affordability and increased in competition. This paper defines and describes the critical PTB parameters and associated requirements that are important to the government SPO for "owning" an affordable COMSATCOM services contract using PPBW trading concept. The paper describes a step-by-step approach to optimally perform the PPBW trading to meet DoD and its stakeholders (i) affordability requirement, and (ii) fixed and variable bandwidth requirements by optimizing communications performance, cost and PPBW accessibility in terms of Quality of Services (QoS), Bandwidth Sharing Ratio (BSR), Committed Information Rate (CIR), Burstable Information Rate (BIR), Transponder equivalent bandwidth (TPE) and transponder Net Presence Value (NPV). The affordable optimal solution that meets variable bandwidth requirements will consider the operating and trading terms and conditions described in the Fair Access Policy (FAP).

  1. Wide baseline stereo matching based on double topological relationship consistency

    Science.gov (United States)

    Zou, Xiaohong; Liu, Bin; Song, Xiaoxue; Liu, Yang

    2009-07-01

    Stereo matching is one of the most important branches in computer vision. In this paper, an algorithm is proposed for wide-baseline stereo vision matching. Here, a novel scheme is presented called double topological relationship consistency (DCTR). The combination of double topological configuration includes the consistency of first topological relationship (CFTR) and the consistency of second topological relationship (CSTR). It not only sets up a more advanced model on matching, but discards mismatches by iteratively computing the fitness of the feature matches and overcomes many problems of traditional methods depending on the powerful invariance to changes in the scale, rotation or illumination across large view changes and even occlusions. Experimental examples are shown where the two cameras have been located in very different orientations. Also, epipolar geometry can be recovered using RANSAC by far the most widely method adopted possibly. By the method, we can obtain correspondences with high precision on wide baseline matching problems. Finally, the effectiveness and reliability of this method are demonstrated in wide-baseline experiments on the image pairs.

  2. Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

    Science.gov (United States)

    Beaton, K. H.; Bloomberg, J. J.

    2014-01-01

    One of the greatest challenges surrounding adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. Such knowledge could guide individually customized countermeasures, which would enable more efficient use of crew time, both preflight and inflight, and provide better outcomes. The primary goal of this project is to look for a baseline performance metric that can forecast sensorimotor adaptability without exposure to an adaptive stimulus. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations in motor performance, as a predictor of individual sensorimotor adaptive capabilities. To-date, a strong relationship has been found between baseline inter-trial correlations and adaptability in two oculomotor systems. For this project, we will explore an analogous predictive mechanism in the locomotion system. METHODS: Baseline Inter-trial Correlations: Inter-trial correlations specify the relationships among repeated trials of a given task that transpire as a consequence of correcting for previous performance errors over multiple timescales. We can quantify the strength of inter-trial correlations by measuring the decay of the autocorrelation function (ACF), which describes how rapidly information from past trials is "forgotten." Processes whose ACFs decay more slowly exhibit longer-term inter-trial correlations (longer memory processes), while processes whose ACFs decay more rapidly exhibit shorterterm inter-trial correlations (shorter memory processes). Longer-term correlations reflect low-frequency activity, which is more easily

  3. Technical note: Effect of determining baseline plasma urea nitrogen concentrations on subsequent posttreatment plasma urea nitrogen concentrations in 20- to 50-kilogram pigs.

    Science.gov (United States)

    Waguespack, A M; Powell, S; Roux, M L; Frugé, E D; Bidner, T D; Payne, R L; Southern, L L

    2011-12-01

    Plasma urea N (PUN) has been used as an indicator of AA requirements and efficiency of AA utilization in swine. However, PUN concentrations vary among a population of pigs, even a population with a close range of BW and fed the same diet. Thus, pretreatment or baseline PUN concentrations are used as a covariate to reduce variation of posttreatment PUN. However, this procedure increases experimental costs and stress to the pigs. Data from 14 experiments (26 to 28 d in duration) conducted using PUN as a response variable were compiled into 1 data set. Each experiment had 4 to 6 treatments. The purpose of this technical report was to summarize the effect of determining pretreatment baseline PUN concentrations on subsequent posttreatment PUN concentrations in 20- to 50-kg pigs. In all experiments, pigs were fed corn- and soybean meal-based diets and low-CP diets with various AA additions; pigs were assigned to dietary treatments in a randomized complete block design with a minimum of 4 replicates of 3 to 5 pigs each. Before the start of each experiment, all pigs were fed a common diet for a minimum of 3 d. Blood samples were collected from each pig before allotment to dietary treatments (d 0) and at the end of each experiment. The baseline (d 0) PUN was analyzed as a covariate for posttreatment PUN. Data from each experiment were analyzed without and with baseline PUN in the statistical model. In all experiments combined, there were 768 possible treatment comparisons. The covariate baseline PUN was statistically significant (P < 0.10) in 9 of 14 experiments. However, only 8 treatment differences changed statistical significance as a result of analyzing the data with baseline PUN as a covariate. These 8 treatment differences were in 3 experiments. These results indicate that it is not always necessary to determine baseline PUN concentrations when feeding diets with large differences in AA content.

  4. Report on diagnosis, treatment and management of an imported falciparum malaria case in Xinjiang%新疆一例输入性恶性疟病例的诊治与处理

    Institute of Scientific and Technical Information of China (English)

    何冰; 王晓蓉; 包拉提别克·斯兰木; 陈访贤; 李玉革

    2013-01-01

    Objective To report the diagnosis,treatment and epidemiological analysis of one case of imported falciparum malaria in Xinjiang,to provide reference of monitoring and control for the imported falciparum malaria in Xinjiang region.Methods One case of imported falciparum malaria at Xinjiang International Travel Healthcare Center was diagnosed through clinical and laboratory testing.The patient was timely treated with artesunate 600 mg five days' therapy and follow-up observed.Results The Equatorial Guinea migrant returnee who appeared the typical malaria symptoms after returning 18 days later.The patient was diagnosed with blood smear detection of Plasmodium falciparum and treated with five days of anti-malarial therapy by oral artesunate upon the confirmed diagnosis.Medical observation and propaganda of prevention on malaria were complemented to the patient and his close contacts.Conclusion Propaganda of anti-malaria knowledge to the persons who are going to malaria-endemic nationas and malaria detection on the returned laborers should be strengthened,so that the malaria infected patients can receive standard treatment timely to avoid the spread of malaria.%目的 对新疆一例输入性恶性疟疾进行诊治及流行病学分析,为新疆输入性疟疾的监测和防治提供参考.方法 对新疆国际旅行卫生保健中心收治的一例输入性恶性疟病例进行诊治及流行病学分析,通过临床、实验室检测明确诊断,及时采用青蒿琥酯600 mg 5日疗法进行治疗并追踪观察.对患者及密切接触者进行疟疾防治知识宣传及医学观察.结果 该病例为赤道几内亚务工归国人员,返回后18d出现典型疟疾发作症状,血涂片检出恶性疟原虫.经用口服青蒿琥酯进行5d抗疟而治愈.结论 应加强赴疟疾流行国家的人员防疟知识的宣传及归国劳务人员的疟疾检测,使患者得到规范治疗,避免疟疾的传播.

  5. A baseline algorithm for face detection and tracking in video

    Science.gov (United States)

    Manohar, Vasant; Soundararajan, Padmanabhan; Korzhova, Valentina; Boonstra, Matthew; Goldgof, Dmitry; Kasturi, Rangachar

    2007-10-01

    Establishing benchmark datasets, performance metrics and baseline algorithms have considerable research significance in gauging the progress in any application domain. These primarily allow both users and developers to compare the performance of various algorithms on a common platform. In our earlier works, we focused on developing performance metrics and establishing a substantial dataset with ground truth for object detection and tracking tasks (text and face) in two video domains -- broadcast news and meetings. In this paper, we present the results of a face detection and tracking algorithm on broadcast news videos with the objective of establishing a baseline performance for this task-domain pair. The detection algorithm uses a statistical approach that was originally developed by Viola and Jones and later extended by Lienhart. The algorithm uses a feature set that is Haar-like and a cascade of boosted decision tree classifiers as a statistical model. In this work, we used the Intel Open Source Computer Vision Library (OpenCV) implementation of the Haar face detection algorithm. The optimal values for the tunable parameters of this implementation were found through an experimental design strategy commonly used in statistical analyses of industrial processes. Tracking was accomplished as continuous detection with the detected objects in two frames mapped using a greedy algorithm based on the distances between the centroids of bounding boxes. Results on the evaluation set containing 50 sequences (~ 2.5 mins.) using the developed performance metrics show good performance of the algorithm reflecting the state-of-the-art which makes it an appropriate choice as the baseline algorithm for the problem.

  6. Gravity sensing with Very Long Baseline Atom Interferometry

    Science.gov (United States)

    Schlippert, Dennis; Albers, Henning; Richardson, Logan L.; Nath, Dipankar; Meiners, Christian; Wodey, Étienne; Schubert, Christian; Ertmer, Wolfgang; Rasel, Ernst M.

    2016-04-01

    Very Long Baseline Atom Interferometry (VLBAI) represents a new class of atom optics experiments with applications in high-accuracy absolute gravimetry, gravity-gradiometry, and for tests of fundamental physics. Extending the baseline of atomic gravimeters from tens of centimeters to several meters opens the route towards competition with superconducting gravimeters. The VLBAI-test stand will consist of a 10m-baseline atom interferometer allowing for free fall times on the order of seconds, which will implemented in the Hannover Institut für Technologie (HITec) of the Leibniz Universität Hannover. In order to suppress environmental noise, the facility utilizes a state-of-the-art vibration isolation platform and a three-layer magnetic shield. We envisage a resolution of local gravitational acceleration of 5 ṡ 10-10 m/s2 with an inaccuracy < 10-9 m/s2. Operation as a gravity-gradiometer will allow to resolve the first-order gravity gradient with a resolution of 5 ṡ 10-10 1/s2. The operation of VLBAI as a differential dual-species gravimeter using ultracold mixtures of ytterbium and rubidium atoms enables quantum tests of the universality of free fall (UFF) at an unprecedented level [1], with the potential to surpass the accuracy of the best experiments to date [2]. We report on the first quantum test of the UFF using two different chemical elements, 39K and 87Rb [3], reaching a 100 ppb inaccuracy and show the potential of UFF tests in VLBAI at an inaccuracy of 10-13 and beyond. References J. Hartwig et al., New J. Phys. 17, 035011- (2015) S. Schlamminger et al., Phys. Rev. Lett. 100, 041101- (2008) D. Schlippert et al., Phys. Rev. Lett. 112, 203002 (2014)

  7. Re-creating missing population baselines for Pacific reef sharks.

    Science.gov (United States)

    Nadon, Marc O; Baum, Julia K; Williams, Ivor D; McPherson, Jana M; Zgliczynski, Brian J; Richards, Benjamin L; Schroeder, Robert E; Brainard, Russell E

    2012-06-01

    Sharks and other large predators are scarce on most coral reefs, but studies of their historical ecology provide qualitative evidence that predators were once numerous in these ecosystems. Quantifying density of sharks in the absence of humans (baseline) is, however, hindered by a paucity of pertinent time-series data. Recently researchers have used underwater visual surveys, primarily of limited spatial extent or nonstandard design, to infer negative associations between reef shark abundance and human populations. We analyzed data from 1607 towed-diver surveys (>1 ha transects surveyed by observers towed behind a boat) conducted at 46 reefs in the central-western Pacific Ocean, reefs that included some of the world's most pristine coral reefs. Estimates of shark density from towed-diver surveys were substantially lower (sharks observed in towed-diver surveys and human population in models that accounted for the influence of oceanic primary productivity, sea surface temperature, reef area, and reef physical complexity. We used these models to estimate the density of sharks in the absence of humans. Densities of gray reef sharks (Carcharhinus amblyrhynchos), whitetip reef sharks (Triaenodon obesus), and the group "all reef sharks" increased substantially as human population decreased and as primary productivity and minimum sea surface temperature (or reef area, which was highly correlated with temperature) increased. Simulated baseline densities of reef sharks under the absence of humans were 1.1-2.4/ha for the main Hawaiian Islands, 1.2-2.4/ha for inhabited islands of American Samoa, and 0.9-2.1/ha for inhabited islands in the Mariana Archipelago, which suggests that density of reef sharks has declined to 3-10% of baseline levels in these areas.

  8. Baseline Gene Expression Signatures in Monocytes from Multiple Sclerosis Patients Treated with Interferon-beta

    Science.gov (United States)

    Bustamante, Marta F.; Nurtdinov, Ramil N.; Río, Jordi; Montalban, Xavier; Comabella, Manuel

    2013-01-01

    Background A relatively large proportion of relapsing-remitting multiple sclerosis (RRMS) patients do not respond to interferon-beta (IFNb) treatment. In previous studies with peripheral blood mononuclear cells (PBMC), we identified a subgroup of IFNb non-responders that was characterized by a baseline over-expression of type I IFN inducible genes. Additional mechanistic experiments carried out in IFNb non-responders suggested a selective alteration of the type I IFN signaling pathway in the population of blood monocytes. Here, we aimed (i) to investigate whether the type I IFN signaling pathway is up-regulated in isolated monocytes from IFNb non-responders at baseline; and (ii) to search for additional biological pathways in this cell population that may be implicated in the response to IFNb treatment. Methods Twenty RRMS patients classified according to their clinical response to IFNb treatment and 10 healthy controls were included in the study. Monocytes were purified from PBMC obtained before treatment by cell sorting and the gene expression profiling was determined with oligonucleotide microarrays. Results and discussion Purified monocytes from IFNb non-responders were characterized by an over-expression of type I IFN responsive genes, which confirms the type I IFN signature in monocytes suggested from previous studies. Other relevant signaling pathways that were up-regulated in IFNb non-responders were related with the mitochondrial function and processes such as protein synthesis and antigen presentation, and together with the type I IFN signaling pathway, may also be playing roles in the response to IFNb. PMID:23637780

  9. Baseline review of the U.S. LHC Accelerator project

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-01

    The Department of Energy (DOE) Review of the U.S. Large Hadron Collider (LHC) Accelerator project was conducted February 23--26, 1998, at the request of Dr. John R. O`Fallon, Director, Division of High Energy Physics, Office of Energy Research, U.S. DOE. This is the first review of the U.S. LHC Accelerator project. Overall, the Committee found that the U.S. LHC Accelerator project effort is off to a good start and that the proposed scope is very conservative for the funding available. The Committee recommends that the project be initially baselined at a total cost of $110 million, with a scheduled completion data of 2005. The U.S. LHC Accelerator project will supply high technology superconducting magnets for the interaction regions (IRs) and the radio frequency (rf) straight section of the LHC intersecting storage rings. In addition, the project provides the cryogenic support interface boxes to service the magnets and radiation absorbers to protect the IR dipoles and the inner triplet quadrupoles. US scientists will provide support in analyzing some of the detailed aspects of accelerator physics in the two rings. The three laboratories participating in this project are Brookhaven National Laboratory, Fermi National Accelerator Laboratory (Fermilab), and Lawrence Berkeley National Laboratory. The Committee was very impressed by the technical capabilities of the US LHC Accelerator project team. Cost estimates for each subsystem of the US LHC Accelerator project were presented to the Review Committee, with a total cost including contingency of $110 million (then year dollars). The cost estimates were deemed to be conservative. A re-examination of the funding profile, costs, and schedules on a centralized project basis should lead to an increased list of deliverables. The Committee concluded that the proposed scope of US deliverables to CERN can be readily accomplished with the $110 million total cost baseline for the project. The current deliverables should serve as

  10. Integrated Baseline System (IBS) Version 1.03: Utilities guide

    Energy Technology Data Exchange (ETDEWEB)

    Burford, M.J.; Downing, T.R.; Pottier, M.C.; Schrank, E.E.; Williams, J.R.

    1993-01-01

    The Integrated Baseline System (IBS) is an emergency management planning and analysis tool that was developed under the direction of the Federal Emergency Management Agency (FEMA). This Utilities Guide explains how to operate utility programs that are supplied as a part of the IBS. These utility programs are chiefly for managing and manipulating various kinds of IBS data and system administration files. Many of the utilities are for creating, editing, converting, or displaying map data and other data that are related to geographic location.

  11. Integrated Baseline System (IBS) Version 2.0: Utilities Guide

    Energy Technology Data Exchange (ETDEWEB)

    Burford, M.J.; Downing, T.R.; Williams, J.R. [Pacific Northwest Lab., Richland, WA (United States); Bower, J.C. [Bower Software Services, Kennewick, WA (United States)

    1994-03-01

    The Integrated Baseline System (IBS) is an emergency management planning and analysis tool being developed under the direction of the US Army Nuclear and Chemical Agency. This Utilities Guide explains how you can use the IBS utility programs to manage and manipulate various kinds of IBS data. These programs include utilities for creating, editing, and displaying maps and other data that are referenced to geographic location. The intended audience for this document are chiefly data managers but also system managers and some emergency management planners and analysts.

  12. Scanner baseliner monitoring and control in high volume manufacturing

    Science.gov (United States)

    Samudrala, Pavan; Chung, Woong Jae; Aung, Nyan; Subramany, Lokesh; Gao, Haiyong; Gomez, Juan-Manuel

    2016-03-01

    We analyze performance of different customized models on baseliner overlay data and demonstrate the reduction in overlay residuals by ~10%. Smart Sampling sets were assessed and compared with the full wafer measurements. We found that performance of the grid can still be maintained by going to one-third of total sampling points, while reducing metrology time by 60%. We also demonstrate the feasibility of achieving time to time matching using scanner fleet manager and thus identify the tool drifts even when the tool monitoring controls are within spec limits. We also explore the scanner feedback constant variation with illumination sources.

  13. Long baseline accelerator neutrino experiments present and future

    CERN Document Server

    Rubbia, André

    2000-01-01

    A nu /sub mu / disappearance effect has been seen in atmospheric neutrino experiments. This has led to the "evidence for neutrino oscillations". The next problem in neutrino physics is to perform the right experiment(s) to elucidate in a comprehensive way the pattern of neutrino masses and mixings. The long baseline experiments will play a fundamental role at settling definitively the question of flavor oscillation and at measuring with good precision the oscillation parameters. The CERN-NGS beam coupled with the proposed ICANOE and OPERA detectors is the only programme capable of sensitive tau and electron appearance searches. (14 refs).

  14. Project W-320 thermal hydraulic model benchmarking and baselining

    Energy Technology Data Exchange (ETDEWEB)

    Sathyanarayana, K.

    1998-09-28

    Project W-320 will be retrieving waste from Tank 241-C-106 and transferring the waste to Tank 241-AY-102. Waste in both tanks must be maintained below applicable thermal limits during and following the waste transfer. Thermal hydraulic process control models will be used for process control of the thermal limits. This report documents the process control models and presents a benchmarking of the models with data from Tanks 241-C-106 and 241-AY-102. Revision 1 of this report will provide a baselining of the models in preparation for the initiation of sluicing.

  15. Emergency Response Capability Baseline Needs Assessment Compliance Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, John A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-09-16

    This document is the second of a two-part analysis of Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2013 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2009 BNA, the 2012 BNA document, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, fire department training records, and fire department policies and procedures.

  16. A FPGA Implementation of JPEG Baseline Encoder for Wearable Devices.

    Science.gov (United States)

    Li, Yuecheng; Jia, Wenyan; Luan, Bo; Mao, Zhi-Hong; Zhang, Hong; Sun, Mingui

    2015-04-01

    In this paper, an efficient field-programmable gate array (FPGA) implementation of the JPEG baseline image compression encoder is presented for wearable devices in health and wellness applications. In order to gain flexibility in developing FPGA-specific software and balance between real-time performance and resources utilization, A High Level Synthesis (HLS) tool is utilized in our system design. An optimized dataflow configuration with a padding scheme simplifies the timing control for data transfer. Our experiments with a system-on-chip multi-sensor system have verified our FPGA implementation with respect to real-time performance, computational efficiency, and FPGA resource utilization.

  17. Future long-baseline neutrino oscillations: View from Europe

    Energy Technology Data Exchange (ETDEWEB)

    Patzak, T. [APC, AstroParticule et Cosmologie, Université Paris Diderot, CNRS/IN2P3, CEA/Irfu, Observatoire de Paris, Sorbonne Paris Cité, 10, rue Alice Domon et Léonie Duquet, 75205 Paris Cedex 13 (France)

    2015-07-15

    Since about a decade the european physics community interested in neutrino and neutrino-astrophysics develops a plan to conceive the next generation large underground neutrino observatory. Recently, the LAGUNA-LBNO collaboration made the outcome of the FP7 design study public which shows a clear path for the realization of such experiment. In this paper the LAGUNA and LAGUNA-LBNO Design studies, resulting in a proposal for the LBNO experiment, will be discussed. The author will focus on the long baseline neutrino oscillation search, especially on the potential to discover the neutrino mass ordering and the search for CP violation in the lepton sector.

  18. Implications of 3+1 short-baseline neutrino oscillations

    Energy Technology Data Exchange (ETDEWEB)

    Giunti, Carlo, E-mail: giunti@to.infn.it [INFN, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Laveder, Marco, E-mail: laveder@pd.infn.it [Dipartimento di Fisica ' ' G. Galilei' ' , Universita di Padova, and INFN, Sezione di Padova, Via F. Marzolo 8, I-35131 Padova (Italy)

    2011-12-06

    We present an upgrade of the 3+1 global fit of short-baseline neutrino oscillation data obtained with the addition of KARMEN and LSND {nu}{sub e}+{sup 12}C{yields}{sup 12}N{sub g.s.}+e{sup -} scattering data. We discuss the implications for the measurements of the effective neutrino mass in {beta}-decay and neutrinoless double-{beta}-decay experiments. We find respective predicted ranges of about 0.1-0.7 eV and 0.01-0.1 eV.

  19. Organic Contamination Baseline Study on NASA JSC Astromaterial Curation Gloveboxes

    Science.gov (United States)

    Calaway, Michael J.; Allton, J. H.; Allen, C. C.; Burkett, P. J.

    2013-01-01

    Future planned sample return missions to carbon-rich asteroids and Mars in the next two decades will require strict handling and curation protocols as well as new procedures for reducing organic contamination. After the Apollo program, astromaterial collections have mainly been concerned with inorganic contamination [1-4]. However, future isolation containment systems for astromaterials, possibly nitrogen enriched gloveboxes, must be able to reduce organic and inorganic cross-contamination. In 2012, a baseline study was orchestrated to establish the current state of organic cleanliness in gloveboxes used by NASA JSC astromaterials curation labs that could be used as a benchmark for future mission designs.

  20. Amlodipine+benazepril is superior to hydrochlorothiazide+benazepril irrespective of baseline pulse pressure: subanalysis of the ACCOMPLISH trial.

    Science.gov (United States)

    Skoglund, Per H; Svensson, Per; Asp, Joline; Dahlöf, Björn; Kjeldsen, Sverre E; Jamerson, Kenneth A; Weber, Michael A; Jia, Yan; Zappe, Dion H; Östergren, Jan

    2015-02-01

    Pulse pressure (PP) is an independent risk factor for cardiovascular (CV) disease and death but few studies have investigated the effect of antihypertensive treatments in relation to PP levels before treatment. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial showed that the combination of benazepril+amlodipine (B+A) is superior to benazepril+hydrochlorothiazide (B+H) in reducing CV events. We aimed to investigate whether the treatment effects in the ACCOMPLISH trial were dependent on baseline PP. High-risk hypertensive patients (n=11,499) were randomized to double-blinded treatment with single-pill combinations of either B+A or B+H and followed for 36 months. Patients were divided into tertiles according to their baseline PP and events (CV mortality/myocardial infarction or stroke) were compared. Hazard ratios (HRs) for the treatment effect (B+A over B+H) were calculated in a Cox regression model with age, coronary artery disease, and diabetes mellitus as covariates and were compared across the tertiles. The event rate was increased in the high tertile of PP compared with the low tertile (7.2% vs 4.4% P<.01). In the high and medium PP tertiles, HRs were 0.75 (95% confidence interval [CI], 0.60-0.95; P=.018) and 0.74 (CI, 0.56-0.98, P=.034), respectively, in favor of B+A. There was no significant difference between the treatments in the low tertile and no significant differences in treatment effect when comparing the HRs between tertiles of PP. B+A has superior CV protection over B+H in high-risk hypertensive patients independent of baseline PP although the absolute treatment effect is enhanced in the higher tertiles of PP where event rates are higher.

  1. Airborne infection control in India: Baseline assessment of health facilities

    Science.gov (United States)

    Parmar, Malik M.; Sachdeva, K.S.; Rade, Kiran; Ghedia, Mayank; Bansal, Avi; Nagaraja, Sharath Burugina; Willis, Matthew D.; Misquitta, Dyson P.; Nair, Sreenivas A.; Moonan, Patrick K.; Dewan, Puneet K.

    2016-01-01

    Background Tuberculosis transmission in health care settings represents a major public health problem. In 2010, national airborne infection control (AIC) guidelines were adopted in India. These guidelines included specific policies for TB prevention and control in health care settings. However, the feasibility and effectiveness of these guidelines have not been assessed in routine practice. This study aimed to conduct baseline assessments of AIC policies and practices within a convenience sample of 35 health care settings across 3 states in India and to assess the level of implementation at each facility after one year. Method A multi-agency, multidisciplinary panel of experts performed site visits using a standardized risk assessment tool to document current practices and review resource capacity. At the conclusion of each assessment, facility-specific recommendations were provided to improve AIC performance to align with national guidelines. Result Upon initial assessment, AIC systems were found to be poorly developed and implemented. Administrative controls were not commonly practiced and many departments needed renovation to achieve minimum environmental standards. One year after the baseline assessments, there were substantial improvements in both policy and practice. Conclusion A package of capacity building and systems development that followed national guidelines substantially improved implementation of AIC policies and practice. PMID:26970461

  2. Baselines for the Pan-Canadian science curriculum framework.

    Science.gov (United States)

    Liu, Xiufeng

    2013-01-01

    Using a Canadian student achievement assessment database, the Science Achievement Indicators Program (SAIP), and employing the Rasch partial credit measurement model, this study estimated the difficulties of items corresponding to the learning outcomes in the Pan-Canadian science curriculum framework and the latent abilities of students of grades 7, 8, 10, 11, 12 and OAC (Ontario Academic Course). The above estimates serve as baselines for validating the Pan-Canadian science curriculum framework in terms of the learning progression of learning outcomes and expected mastery of learning outcomes by grades. It was found that there was no statistically significant progression in learning outcomes from grades 4-6 to grades 7-9, and from grades 7-9 to grades 10-12; the curriculum framework sets mastery expectation about 2 grades higher than students' potential abilities. In light of the above findings, this paper discusses theoretical issues related to deciding progression of learning outcomes and setting expectation of student mastery of learning outcomes, and highlights the importance of using national assessment data to establish baselines for the above purposes. This paper concludes with recommendations for further validating the Pan-Canadian science curriculum frameworks.

  3. The IUGS/IAGC Task Group on Global Geochemical Baselines

    Science.gov (United States)

    Smith, David B.; Wang, Xueqiu; Reeder, Shaun; Demetriades, Alecos

    2012-01-01

    The Task Group on Global Geochemical Baselines, operating under the auspices of both the International Union of Geological Sciences (IUGS) and the International Association of Geochemistry (IAGC), has the long-term goal of establishing a global geochemical database to document the concentration and distribution of chemical elements in the Earth’s surface or near-surface environment. The database and accompanying element distribution maps represent a geochemical baseline against which future human-induced or natural changes to the chemistry of the land surface may be recognized and quantified. In order to accomplish this long-term goal, the activities of the Task Group include: (1) developing partnerships with countries conducting broad-scale geochemical mapping studies; (2) providing consultation and training in the form of workshops and short courses; (3) organizing periodic international symposia to foster communication among the geochemical mapping community; (4) developing criteria for certifying those projects whose data are acceptable in a global geochemical database; (5) acting as a repository for data collected by those projects meeting the criteria for standardization; (6) preparing complete metadata for the certified projects; and (7) preparing, ultimately, a global geochemical database. This paper summarizes the history and accomplishments of the Task Group since its first predecessor project was established in 1988.

  4. Does Baseline Heart Rate Variability Reflect Stable Positive Emotionality?

    Science.gov (United States)

    Silvia, Paul J; Jackson, Bryonna A; Sopko, Rachel S

    2014-11-01

    Several recent studies have found significant correlations, medium in effect size, between baseline heart rate variability (HRV) and measures of positive functioning, such as extraversion, agreeableness, and trait positive affectivity. Other research, however, has suggested an optimal level of HRV and found nonlinear effects. In the present study, a diverse sample of 239 young adults completed a wide range of measures that reflect positive psychological functioning, including personality traits, an array of positive emotions (measured with the Dispositional Positive Emotions Scale), and depression, anxiety, and stress symptoms (measured with the DASS and CESD). HRV was measured with a 6-minute baseline period and quantified using many common HRV metrics (e.g., respiratory sinus arrhythmia, root mean square of successive differences, and others), and potentially confounding behavioral and lifestyle variables (e.g., BMI, caffeine and nicotine use, sleep quality) were assessed. Neither linear nor non-linear effects were found, and the effect sizes were small and near zero. The findings suggest that the cross-sectional relationship between HRV and positive experience deserves more attention and meta-analytic synthesis.

  5. The IUGS/IAGC Task Group on Global Geochemical Baselines

    Institute of Scientific and Technical Information of China (English)

    David B.Smith; Shaun Reeder; Alecos Demetriades

    2012-01-01

    The Task Group on Global Geochemical Baselines,operating under the auspices of both the International Union of Geological Sciences(IUGS) and the International Association of Geochemistry(IAGC),has the long-term goal of establishing a global geochemical database to document the concentration and distribution of chemical elements in the Earth's surface or near-surface environment.The database and accompanying element distribution maps represent a geochemical baseline against which future human-induced or natural changes to the chemistry of the land surface may be recognized and quantified.In order to accomplish this long-term goal,the activities of the Task Group include:(1) developing partnerships with countries conducting broad-scale geochemical mapping studies;(2) providing consultation and training in the form of workshops and short courses;(3) organizing periodic international symposia to foster communication among the geochemical mapping community;(4) developing criteria for certifying those projects whose data are acceptable in a global geochemical database;(5) acting as a repository for data collected by those projects meeting the criteria for standardization;(6) preparing complete metadata for the certified projects;and(7) preparing,ultimately,a global geochemical database.This paper summarizes the history and accomplishments of the Task Group since its first predecessor project was established in 1988.

  6. EMD-based GPS baseline solution and validation test

    Institute of Scientific and Technical Information of China (English)

    WANG Jian; GAO Jing-xiang; WANG Jin-ling; XU Chang-hui

    2008-01-01

    A GPS baseline solution model is presented, based on the Empirical Mode Decomposition (EMD), which has the advantage of eliminating the error effects outside the model. The EMD technique is a new signal processing method for non-linear time series, which decomposes a time series into a finite and often small number of Intrinsic Mode Functions (IMFs). The decomposition procedure is adaptive and data-driven which is suitable for non-linear data series analysis. A multi-scale decomposition and reconstruction architecture is defined on the basis of the EMD theory and the error mitigation model is demonstrated as well. A standard of the scale selection for the elimination of errors, outside the model, was given in terms of the mean of the accumulated standardized modes. Thereafter, the scheme of the GPS baseline solution based on the EMD is suggested. The float solution residuals of the Double-Difference (DD) observation equation are used to extract the errors outside the model applied to modify the GPS DD measurements. Then the float solution was given again and the fixed solution was obtained by a Lambda algorithm. Three schemes are designed to test the proposed model and the experimental results show that the proposed model dramatically improves the relia- bility of ambiguity resolution after the elimination of errors outside the model.

  7. Study of neutrino oscillations in long-baseline accelerator experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kudenko, Yurii G [Institute for Nuclear Research, Russian Academy of Sciences, Moscow (Russian Federation)

    2011-06-30

    A review of the title subject is given. The phenomenology of neutrino oscillations in the framework of the so-called neutrino Standard Model ({nu}SM) with three active neutrinos is considered. The recently completed long-baseline accelerator experiment K2K and currently in-progress MINOS and OPERA experiments are described in detail. The oscillation parameters obtained from the global analysis of all oscillation data are given. The short-baseline experiment MiniBooNE and its results on the search for light sterile neutrinos are discussed in detail. Considerable attention is given to searching for {nu}{sub {mu}{yields}{nu}e} oscillations and measuring the {theta}{sub 13} angle in muon neutrino experiments. The concept of the off-axis neutrino beam is reviewed. The T2K experiment, collecting statistics since early 2010, is described for its details and objectives. The NO{nu}A experiment under construction and the next-generation beta beam and neutrino factory experiments are also discussed. (reviews of topical problems)

  8. A baseline for the multivariate comparison of resting state networks

    Directory of Open Access Journals (Sweden)

    Elena A Allen

    2011-02-01

    Full Text Available As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting state networks of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12 to 71 years. Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. Resting state networks were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

  9. Verification and optimization of the CFETR baseline scenario

    Science.gov (United States)

    Zhao, D.; Lao, L. L.; Meneghini, O.; Staebler, G. M.; Candy, J.; Smith, S. P.; Snyder, P. B.; Prater, R.; Chen, X.; Chan, V. S.; Li, J.; Chen, J.; Shi, N.; Guo, W.; Pan, C.; Jian, X.

    2016-10-01

    The baseline scenario of China Fusion Engineering Test Reactor (CFETR) was designed starting from 0D calculations. The CFETR baseline scenario satisfies the minimum goal of Fusion Nuclear Science Facility aimed at bridging the gaps between ITER and DEMO. 1.5D calculations are presented to verify the on-going efforts in higher-dimensional modeling of CFETR. Steady-state scenarios are calculated self-consistently by the OMFIT integrated modeling framework that includes EFIT for equilibrium, ONETWO for sources and current, TGYRO for transport. With 68MW of neutral beam power and 8MW of ECH injected to the plasma, the average ion temperature is maintained at 15keV, while 150MW fusion power is produced. The neutral beams also drive 55% of the plasma current. Modest fast ion diffusion will reduce NBCD and affect the profile substantially. Top-launch ECH will increase the current drive and the power absorption rate. EPED model are being included. Work supported by U.S. DOE under DE-FC02-04ER54698 and the USTC CFETR contract.

  10. The mixed waste management facility. Project baseline revision 1.2

    Energy Technology Data Exchange (ETDEWEB)

    Streit, R.D.; Throop, A.L.

    1995-04-01

    Revision 1.2 to the Project Baseline (PB) for the Mixed Waste Management Facility (MWMF) is in response to DOE directives and verbal guidance to (1) Collocate the Decontamination and Waste Treatment Facility (DWTF) and MWMF into a single complex, integrate certain and overlapping functions as a cost-saving measure; (2) Meet certain fiscal year (FY) new-BA funding objectives ($15.3M in FY95) with lower and roughly balanced funding for out years; (3) Reduce Total Project Cost (TPC) for the MWMF Project; (4) Include costs for all appropriate permitting activities in the project TPC. This baseline revision also incorporates revisions in the technical baseline design for Molten Salt Oxidation (MSO) and Mediated Electrochemical Oxidation (MEO). Changes in the WBS dictionary that are necessary as a result of this rebaseline, as well as minor title changes, at WBS Level 3 or above (DOE control level) are approved as a separate document. For completeness, the WBS dictionary that reflects these changes is contained in Appendix B. The PB, with revisions as described in this document, were also the basis for the FY97 Validation Process, presented to DOE and their reviewers on March 21-22, 1995. Appendix C lists information related to prior revisions to the PB. Several key changes relate to the integration of functions and sharing of facilities between the portion of the DWTF that will house the MWMF and those portions that are used by the Hazardous Waste Management (HWM) Division at LLNL. This collocation has been directed by DOE as a cost-saving measure and has been implemented in a manner that maintains separate operational elements from a safety and permitting viewpoint. Appendix D provides background information on the decision and implications of collocating the two facilities.

  11. Infrequency of asymptomatic malaria in an endemic area in Amazonas, Brazil

    Directory of Open Access Journals (Sweden)

    Aluizio Prata

    1988-06-01

    Full Text Available A malaria survey was conducted in an area of high transmission (Costa Marques, Rondonia, Brazil to determine the prevalence of asymptomatic parasitemia and its clinical significance. Most of the people surveyed were immigrants who had lived in the endemic area 2 days, 4 had only gametocytes, 1 had taken inadequate anti-malarial treatment, 3 were under treatment and 2 moved. Six asymptomatic patients denied the use of anti-malarial drugs and they developed malaria 3-6 days after the initial parasitological diagnosis. The final patient remained asymptomatic during the 7 day observation period. He had a history of > 40 malaria attacks and denied the use of antimalarial treatment. With the exception of the latter all of the other asymptomatic patients, were either in the incubation period or had been treated It is concluded that asymptomatic malaria is rare in the Costa Marques area and that it is necessary to treat all individuals with plasmodial parasitemia.

  12. CP violation and matter effect for a variable earth density in very long baseline experiments

    Energy Technology Data Exchange (ETDEWEB)

    Brahmachari, Biswajoy; Choubey, Sandhya E-mail: sandhya@he.sissa.it; Roy, Probir

    2003-11-03

    The perturbative treatment of subdominant oscillation and matter effect in neutrino beams/superbeams, propagating over long baselines and being used to look for CP violation, is studied here for a general matter density function varying with distance. New lowest order analytic expressions are given for different flavour transition and survival probabilities in a general neutrino mixing basis and a variable earth matter density profile. It is demonstrated that the matter effect in the muon neutrino (antineutrino) flavour survival probability vanishes to this order, provided the depletion, observed for atmospheric muon neutrinos and antineutrinos at super-Kamiokande, is strictly maximal. This result is independent of the earth density profile and the distance L between the source and the detector. In the general variable density case we show that one cannot separate the matter induced asymmetry from a genuine CP effect by keeping two detectors at distances L{sub 1} and L{sub 2} from the source while maintaining a fixed ratio L{sub 1}/E{sub 1}=L{sub 2}/E{sub 2}. This needs to be done numerically and we estimate the asymmetry generated by the earth matter effect with particular density profiles and some chosen parameters for very long baseline neutrino oscillation experiments.

  13. Improvement during baseline: three case studies encouraging collaborative research when evaluating caregiver training.

    Science.gov (United States)

    Sohlberg, M M; Glang, A; Todis, B

    1998-04-01

    The trend in cognitive rehabilitation toward reduced services, which provide more functionally relevant outcomes and the recognition of limited maintenance and generalization with many existing interventions, challenges current research models. There is a need to develop and evaluate interventions that can be implemented by persons other than rehabilitation professionals and that are well suited to naturalistic settings. The researchers responded to these challenges by designing a series of single subject experiments evaluating the effectiveness of training caregivers to provide appropriate cognitive support to persons with brain injury within their own natural living environments. The goal of the original research project included evaluating a collaborative mode of interaction with the subjects and their support persons (as opposed to traditional directive treatment models) where the caregivers and subjects were instrumental in designing the intervention and collective performance data. This paper presents the data from the initial three subject/caregiver groups all of whom demonstrated improvement in the target behaviours during the baseline period. It appeared that the act of measuring client performance changed the behaviours of the support persons and resulted in positive changes in baseline levels. The research and clinical implications of these findings are discussed.

  14. Adapting a Cryogenic Sapphire Oscillator for Very Long Baseline Interferometry

    CERN Document Server

    Doeleman, Sheperd; Rogers, Alan; Hartnett, John; Tobar, Michael; Nand, Nitin; 10.1086/660156

    2011-01-01

    Extension of very long baseline interferometry (VLBI) to observing wavelengths shorter than 1.3mm provides exceptional angular resolution (~20 micro arcsec) and access to new spectral regimes for the study of astrophysical phenomena. To maintain phase coherence across a global VLBI array at these wavelengths requires that ultrastable frequency references be used for the heterodyne receivers at all participating telescopes. Hydrogen masers have traditionally been used as VLBI references, but atmospheric turbulence typically limits (sub) millimeter VLBI coherence times to ~1-30 s. Cryogenic Sapphire Oscillators (CSO) have better stability than Hydrogen masers on these time scale and are potential alternatives to masers as VLBI references. Here, We describe the design, implementation and tests of a system to produce a 10 MHz VLBI frequency standard from the microwave (11.2 GHz) output of a CSO. To improve long-term stability of the new reference, the CSO was locked to the timing signal from the Global Positionin...

  15. Short-baseline neutrino oscillations, Planck, and IceCube

    CERN Document Server

    Cherry, John F; Shoemaker, Ian M

    2016-01-01

    We examine a framework with light new physics, which couples to the Standard Model only via neutrino mixing. Taking the hints from the short-baseline anomalies seriously and combining them with modern cosmological data and recent IceCube measurements, we obtain surprisingly effective constraints on the hidden force: keV $\\lesssim M \\lesssim0.3$ GeV for the mediator mass and $g_{h}>10^{-6}-10^{-3}$ for the coupling constant. Flavor equilibration between the hidden and active neutrinos can be delayed until temperatures of $\\sim 1$ MeV, but not below $\\sim 100$ keV. This scenario can be tested with next-generation Cosmic Microwave Background, IceCube, and oscillation experiments.

  16. Compression phase study of the HiPER baseline target

    Energy Technology Data Exchange (ETDEWEB)

    Ribeyre, X; Nicolai, Ph; Schurtz, G; Olazabal-Loume, M; Breil, J; Maire, P H; Feugeas, J L; Hallo, L; Tikhonchuk, V T [Centre Lasers Intenses et Applications, Universite Bordeaux 1, CNRS, CEA, Universite Bordeaux 1, 351, cours de la Liberation, 33405 Talence (France)

    2008-02-15

    The European High Power laser Energy Research (HiPER) project aims at demonstrating the feasibility of high gain inertial confinement fusion using the fast ignitor approach. A baseline target has been recently developed by Atzeni et al (2007 Phys. Plasmas 14 052702). We study here the robustness of this target during the compression phase and define pulse shape tolerances for a successful fuel assembly. The comparison between a standard and a relaxation pulse shows that the latter allows one to reduce both the laser power contrast and the growth of perturbations due to Rayleigh-Taylor instability. We have found that with 95 kJ of absorbed laser energy one can assemble the fuel with a peak density around 500 g cm{sup -2} and a peak areal density of 1.2 g cm{sup -2}. This implies a total target gain of about 60.

  17. Numerical simulations of the HiPER baseline target

    Energy Technology Data Exchange (ETDEWEB)

    Ribeyre, X; Nicolai, P; Schurtz, G; Olazabal-Loume, M; Breil, J; Maire, P H; Feugeas, J L; Hallo, L; Tikhonchuk, V T [Centre Lasers Intenses et Applications, Universite Bordeaux 1, CNRS, CEA, Universite Bordeaux 1, 351, cours de la Liberation, 33405 Talence (France)], E-mail: ribeyre@celia.u-bordeaux1

    2008-05-15

    The European High Power laser Energy Research (HiPER) project aims at demonstrating the feasibility of high gain inertial confinement fusion (ICF) using the fast ignitor approach. A baseline target has been recently developed by Atzeni et al. [Phys. Plasmas 14, 052702 (2007)]. The comparison between a standard and a relaxation pulse shows that the latter one allows to reduce both the laser power contrast and the growth of perturbation under Rayleigh-Taylor instability. We have found that with 95 kJ of absorbed laser energy one can assemble the fuel with to a peak density around 500 g/cm{sup 3} and to a peak areal density of 1.2 g/cm{sup 2}. This implies a total target gain of about 55.

  18. Numerical simulations of the HiPER baseline target

    Energy Technology Data Exchange (ETDEWEB)

    Ribeyre, X.; Nicolai, Ph.; Schurtz, G.; Olazabal-Loume, M.; Breil, J.; Maire, P.H.; Feugeas, J.M.; Hallo, L.; Tikhonchuk, V.T. [Bordeaux-1 Univ., Centre Lasers Intenses et Applications, CNRS, CEA, 33 - Talence (France)

    2009-08-15

    The European High Power laser Energy Research (HiPER) project aims at demonstrating the feasibility of high gain inertial confinement fusion using the fast ignitor approach. A baseline target has been recently developed by Atzeni et al. [Phys. Plasmas 14, 052702 (2007)]. The radiative transport have a minor effect on the peak areal density but decreased by 20% the peak density. We have found that with 95 kJ of absorbed laser energy one can assemble the fuel with a peak density around 500 g/cm{sup 3} and a peak areal density of 1.2 g/cm{sup 2}. This implies a total target gain of about 60. (authors)

  19. Emergency Response Capability Baseline Needs Assessment - Compliance Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, John A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-09-01

    This document was prepared by John A. Sharry, LLNL Fire Marshal and Division Leader for Fire Protection and was reviewed by LLNL Emergency Management Department Head, James Colson. This document is the second of a two-part analysis on Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2016 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2016 BNA, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, fire department training records, and fire department policies and procedures. The 2013 BNA was approved by NNSA’s Livermore Field Office on January 22, 2014.

  20. Electricity End Uses, Energy Efficiency, and Distributed Energy Resources Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Lisa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wei, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Morrow, William [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Deason, Jeff [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schiller, Steven R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Leventis, Greg [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Smith, Sarah [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Leow, Woei Ling [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Levin, Todd [Argonne National Lab. (ANL), Argonne, IL (United States); Plotkin, Steven [Argonne National Lab. (ANL), Argonne, IL (United States); Zhou, Yan [Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)

    2017-01-01

    This report was developed by a team of analysts at Lawrence Berkeley National Laboratory, with Argonne National Laboratory contributing the transportation section, and is a DOE EPSA product and part of a series of “baseline” reports intended to inform the second installment of the Quadrennial Energy Review (QER 1.2). QER 1.2 provides a comprehensive review of the nation’s electricity system and cover the current state and key trends related to the electricity system, including generation, transmission, distribution, grid operations and planning, and end use. The baseline reports provide an overview of elements of the electricity system. This report focuses on end uses, electricity consumption, electric energy efficiency, distributed energy resources (DERs) (such as demand response, distributed generation, and distributed storage), and evaluation, measurement, and verification (EM&V) methods for energy efficiency and DERs.

  1. Laser-Ranging Long Baseline Differential Atom Interferometers for Space

    CERN Document Server

    Chiow, Sheng-wey; Yu, Nan

    2015-01-01

    High sensitivity differential atom interferometers are promising for precision measurements in science frontiers in space, including gravity field mapping for Earth science studies and gravitational wave detection. We propose a new configuration of twin atom interferometers connected by a laser ranging interferometer (LRI-AI) to provide precise information of the displacements between the two AI reference mirrors and a means to phase-lock the two independent interferometer lasers over long distances, thereby further enhancing the feasibility of long baseline differential atom interferometers. We show that a properly implemented LRI-AI can achieve equivalent functionality to the conventional differential atom interferometer measurement system. LRI-AI isolates the laser requirements for atom interferometers and for optical phase readout between distant locations, thus enabling optimized allocation of available laser power within a limited physical size and resource budget. A unique aspect of LRI-AI also enables...

  2. Baseline projections of transportation energy consumption by mode: 1981 update

    Energy Technology Data Exchange (ETDEWEB)

    Millar, M; Bunch, J; Vyas, A; Kaplan, M; Knorr, R; Mendiratta, V; Saricks, C

    1982-04-01

    A comprehensive set of activity and energy-demand projections for each of the major transportation modes and submodes is presented. Projections are developed for a business-as-usual scenario, which provides a benchmark for assessing the effects of potential conservation strategies. This baseline scenario assumes a continuation of present trends, including fuel-efficiency improvements likely to result from current efforts of vehicle manufacturers. Because of anticipated changes in fuel efficiency, fuel price, modal shifts, and a lower-than-historic rate of economic growth, projected growth rates in transportation activity and energy consumption depart from historic patterns. The text discusses the factors responsible for this departure, documents the assumptions and methodologies used to develop the modal projections, and compares the projections with other efforts.

  3. Baseline Requirements and Architecture for Cloud Computing Services

    Directory of Open Access Journals (Sweden)

    Abdur Rahim Choudhary

    2012-12-01

    Full Text Available Government initiatives such as the “Cloud First” policy are bringing the cloud computing services into Federal Agencies. Further, many of the sectors in the Critical Infrastructure of the nation already use cloud computing. Although cloud computing services are slowly coming to age, many issues remain. This paper therefore takes a closer look at the cloud computing services. First it establishes a baseline by specifying high level requirements for cloud computing services. Next it improves upon the current architecture for the cloud computing services by adding new modules to the current architecture. The new modules are gleaned from an analysis of the telecommunications cloud and security in distributed systems. The new modules include a management and control network, a set of trust domains, and a set of proxies. The improved architecture is more ready for primetime use and supports a richer operational model.

  4. Waste Assessment Baseline for the IPOC Second Floor, West Wing

    Energy Technology Data Exchange (ETDEWEB)

    McCord, Samuel A [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Waste Management and Pollution Prevention

    2015-04-01

    Following a building-wide waste assessment in September, 2014, and subsequent presentation to Sandia leadership regarding the goal of Zero Waste by 2025, the occupants of the IPOC Second Floor, West Wing contacted the Materials Sustainability and Pollution Prevention (MSP2) team to guide them to Zero Waste in advance of the rest of the site. The occupants are from Center 3600, Public Relations and Communications , and Center 800, Independent Audit, Ethics and Business Conduct . To accomplish this, MSP2 conducted a new limited waste assessment from March 2-6, 2015 to compare the second floor, west wing to the building as a whole. The assessment also serves as a baseline with which to mark improvements in diversion in approximately 6 months.

  5. Baseline patient characteristics and mortality associated with longitudinal intervention compliance.

    Science.gov (United States)

    Lin, Julia Y; Ten Have, Thomas R; Bogner, Hillary R; Elliott, Michael R

    2007-12-10

    Lin et al. (http://www.biostatsresearch.com/upennbiostat/papers/, 2006) proposed a nested Markov compliance class model in the Imbens and Rubin compliance class model framework to account for time-varying subject noncompliance in longitudinal randomized intervention studies. We use superclasses, or latent compliance class principal strata, to describe longitudinal compliance patterns, and time-varying compliance classes are assumed to depend on the history of compliance. In this paper, we search for good subject-level baseline predictors of these superclasses and also examine the relationship between these superclasses and all-cause mortality. Since the superclasses are completely latent in all subjects, we utilize multiple imputation techniques to draw inferences. We apply this approach to a randomized intervention study for elderly primary care patients with depression.

  6. Precise geodesy with the Very Long Baseline Array

    CERN Document Server

    Petrov, Leonid; Gipson, John; MacMillan, Dan; Ma, Chopo; Fomalont, Ed; Walker, R Craig; Carabajal, Claudia

    2008-01-01

    We report on a program of regular measurements between 1994 and 2007 which used the Very Long Baseline Array and up to 10 additional stations. One of the goals of these sessions was to monitor positions of the array at 1 millimeter level of accuracy and to tie the VLBA into the International Terrestrial Reference Frame. The large number of stations and the many competing goals made scheduling these sessions manually difficult, and lead to advances in scheduling software. We describe the analysis of these data, which is non-standard, and involves translating the data into a form useful for geodetic VLBI. We also describe several interesting geophysical results including measured station displacement due to crustal motion, earthquakes, and antenna tilt. In terms of both formal errors and observed scatter, these sessions are among the very best geodetic VLBI sessions.

  7. Report of the US long baseline neutrino experiment study

    CERN Document Server

    Barger, V; Bogert, D; Bromberg, C; Curioni, A; Dierckxsens, M; Diwan, M; Dufour, F; Finley, D; Fleming, B T; Gallardo, J; Heim, J; Huber, P; Jung, C K; Kahn, S; Kearns, E; Kirk, H; Kirk, T; Lande, K; Laughton, C; Lee, W Y; Lesko, K; Lewis, C; Litchfield, P J; Mann, A K; Marchionni, A; Marciano, W; Marfatia, D; Marino, A D; Marshak, M; Menary, S; McDonald, K; Messier, M; Pariseau, W; Parsa, Z; Pordes, S; Potenza, R; Rameika, R; Saoulidou, N; Simos, N; Van Berg, R; Viren, B; Whisnant, K; Wilson, R; Winter, W; Yanagisawa, C; Yumiceva, F; Zimmerman, E D; Zwaska, R

    2007-01-01

    This report provides the results of an extensive and important study of the potential for a U.S. scientific program that will extend our knowledge of neutrino oscillations well beyond what can be anticipated from ongoing and planned experiments worldwide. The program examined here has the potential to provide the U.S. particle physics community with world leading experimental capability in this intensely interesting and active field of fundamental research. Furthermore, this capability could be unique compared to anywhere else in the world because of the available beam intensity and baseline distances. The present study was initially commissioned in April 2006 by top research officers of Brookhaven National Laboratory and Fermi National Accelerator Laboratory and, as the study evolved, it also provided responses to questions formulated and addressed to the study group by the Neutrino Scientific Advisory Committee (NuSAG) of the U.S. DOE and NSF. The participants in the study, its Charge and history, plus the ...

  8. Direct coal liquefaction baseline design and system analysis

    Energy Technology Data Exchange (ETDEWEB)

    1991-04-01

    The primary objective of the study is to develop a computer model for a base line direct coal liquefaction design based on two stage direct coupled catalytic reactors. This primary objective is to be accomplished by completing the following: a base line design based on previous DOE/PETC results from Wilsonville pilot plant and other engineering evaluations; a cost estimate and economic analysis; a computer model incorporating the above two steps over a wide range of capacities and selected process alternatives; a comprehensive training program for DOE/PETC Staff to understand and use the computer model; a thorough documentation of all underlying assumptions for baseline economics; and a user manual and training material which will facilitate updating of the model in the future.

  9. Sandia National Laboratories, California proposed CREATE facility environmental baseline survey.

    Energy Technology Data Exchange (ETDEWEB)

    Catechis, Christopher Spyros

    2013-10-01

    Sandia National Laboratories, Environmental Programs completed an environmental baseline survey (EBS) of 12.6 acres located at Sandia National Laboratories/California (SNL/CA) in support of the proposed Collaboration in Research and Engineering for Advanced Technology and Education (CREATE) Facility. The survey area is comprised of several parcels of land within SNL/CA, County of Alameda, California. The survey area is located within T 3S, R 2E, Section 13. The purpose of this EBS is to document the nature, magnitude, and extent of any environmental contamination of the property; identify potential environmental contamination liabilities associated with the property; develop sufficient information to assess the health and safety risks; and ensure adequate protection for human health and the environment related to a specific property.

  10. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

    Science.gov (United States)

    McMurray, John J.V.; Anand, Inder S.; Diaz, Rafael; Maggioni, Aldo P.; O'Connor, Christopher; Pfeffer, Marc A.; Solomon, Scott D.; Tendera, Michal; van Veldhuisen, Dirk J.; Albizem, Moetaz; Cheng, Sunfa; Scarlata, Debra; Swedberg, Karl; Young, James B.; Amuchastegui, M.; Belziti, C.; Bluguermann, J.; Caccavo, M.; Cartasegna, L.; Colque, R.; Cuneo, C.; Fernandez, A.; Gabito, A.; Goicochea, R.; Gonzalez, M.; Gorosito, V.; Grinfeld, L.; Hominal, M.; Kevorkian, R.; Litvak Bruno, M.; Llanos, J.; Mackinnon, I.; Manuale, O.; Marzetti, E.; Nul, D.; Perna, E.; Riccitelli, M.; Sanchez, A.; Santos, D.; Schygiel, P.; Toblli, J.; Vogel, D.; Aggarwal, A.; Amerena, J.; De Looze, F.; Fletcher, P.; Hare, D.; Ireland, M.; Krum, H.; Lattimore, J.; Marwick, T.; Sindone, A.; Thompson, P.; Waites, J.; Altenberger, J.; Ebner, C.; Lenz, K.; Pacher, R.; Poelzl, G.; Charlier, F.; de Ceuninck, M.; De Keulenaer, G.; Dendale, P.; Maréchal, P.; Mullens, W.; Thoeng, J.; Vanderheyden, M.; Vanhaecke, J.; Weytjens, C.; Wollaert, B.; Albuquerque, D.; Almeida, D.; Aspe y Rosas, J.; Bocchi, E.; Bordignon, S.; Clausell, N.; Kaiser, S.; Leaes, P.; Martins Alves, S.; Montera, M.; Moura, L.; Pereira de Castro, R.; Rassi, S.; Reis, A.; Saraiva, J.; Simões, M.; Souza Neto, J.; Teixeira, M.; Benov, H.; Chompalova, B.; Donova, T.; Georgiev, P.; Gotchev, D.; Goudev, A.; Grigorov, M.; Guenova, D.; Hergeldjieva, V.; Ivanov, D.; Kostova, E.; Manolova, A.; Marchev, S.; Nikolov, F.; Popov, A.; Raev, D.; Tzekova, M.; Czarnecki, W.; Giannetti, N.; Haddad, H.; Heath, J.; Huynh, T.; Lepage, S.; Liu, P.; Lonn, E.; Ma, P.; Manyari, D.; Moe, G.; Parker, J.; Pesant, Y.; Rajda, M.; Ricci, J.; Roth, S.; Sestier, F.; Sluzar, V.; Sussex, B.; Vizel, S.; Antezana, G.; Bugueno, C.; Castro, P.; Conejeros, C.; Manriquez, L.; Martinez, D.; Potthoff, S.; Stockins, B.; Vukasovic, J.; Gregor, P.; Herold, M.; Jerabek, O.; Jirmar, R.; Kuchar, R.; Linhart, A.; Podzemska, B.; Soucek, M.; Spac, J.; Spacek, R.; Vodnansky, P.; Bronnum-Schou, J.; Clemmensen, K.; Egstrup, K.; Jensen, G.; Kjoller-Hansen, L.; Kober, L.; Markenvard, J.; Rokkedal, J.; Skagen, K.; Torp-Pedersen, C.; Tuxen, C.; Videbak, L.; Laks, T.; Vahula, V.; Harjola, V.; Kettunen, R.; Kotila, M.; Bauer, F.; Cohen Solal, A.; Coisne, D.; Davy, J.; De Groote, P.; Dos Santos, P.; Funck, F.; Galinier, M.; Gibelin, P.; Isnard, R.; Neuder, Y.; Roul, G.; Sabatier, R.; Trochu, J.; Anker, S.; Denny, S.; Dreykluft, T.; Flesch, M.; Genth-Zotz, S.; Hambrecht, R.; Hein, J.; Jeserich, M.; John, M.; Kreider-Stempfle, H.; Laufs, U.; Muellerleile, K.; Natour, M.; Sandri, M.; Schäufele, T.; von Hodenberg, E.; Weyland, K.; Winkelmann, B.; Tse, H.; Yan, B.; Barsi, B.; Csikasz, J.; Dezsi, C.; Edes, I.; Forster, T.; Karpati, P.; Kerekes, C.; Kis, E.; Kosa, I.; Lupkovics, G.; Nagy, A.; Preda, I.; Ronaszeki, A.; Tomcsanyi, J.; Zamolyi, K.; Agarwal, D.; Bahl, V.; Bordoloi, A.; Chockalingam, K.; Chopda, M.; Chopra, V.; Dugal, J.; Ghaisas, N.; Ghosh, S.; Grant, P.; Hiremath, S.; Iyengar, S.; Jagadeesa Subramania, B.; Jain, P.; Joshi, A.; Khan, A.; Mullasari, A.; Naik, S.; Oomman, A.; Pai, V.; Pareppally Gopal, R.; Parikh, K.; Patel, T.; Prakash, V.; Sastry, B.; Sathe, S.; Sinha, N.; Srikanthan, V.; Subburamakrishnan, P.; Thacker, H.; Wander, G.; Admon, D.; Katz, A.; Klainman, E.; Lewis, B.; Marmor, A.; Moriel, M.; Mosseri, M.; Shotan, A.; Weinstein, J.; Zimlichman, R.; Agostoni, P.; Albanese, M.; Alunni, G.; Bini, R.; Boccanelli, A.; Bolognese, L.; Campana, C.; Carbonieri, E.; Carpino, C.; Checco, L.; Cosmi, F.; D'Angelo, G.; De Cristofaro, M.; Floresta, A.; Fucili, A.; Galvani, M.; Ivleva, A.; Marra, S.; Musca, G.; Peccerillo, N.; Perrone Filardi, P.; Picchio, E.; Russo, T.; Scelsi, L.; Senni, M.; Tavazzi, L.; Erglis, A.; Jasinkevica, I.; Kakurina, N.; Veze, I.; Volans, E.; Bagdonas, A.; Berukstis, E.; Celutkiene, J.; Dambrauskaite, A.; Jarasuniene, D.; Luksiene, D.; Rudys, A.; Sakalyte, G.; Sliaziene, S.; Aguilar-Romero, R.; Cardona-Muñoz, E.; Castro-Jimenez, J.; Chavez-Herrera, J.; Chuquiure Valenzuela, E.; De la Pena, G.; Herrera, E.; Leiva-Pons, J.; Lopez Alvarado, A.; Mendez Machado, G.; Ramos-Lopez, G.; Basart, D.; Buijs, E.; Cornel, J.; de Leeuw, M.; Dijkgraaf, R.; Dunselman, P.; Freericks, M.; Hamraoui, K.; Lenderlink, T.; Linssen, G.; Lodewick, P.; Lodewijks, C.; Lok, D.; Nierop, P.; Ronner, E.; Somsen, A.; van Dantzig, J.; van der Burgh, P.; van Kempen, L.; van Vlies, B.; Voors, A.; Wardeh, A.; Willems, F.; Dickstein, K.; Gundersen, T.; Hole, T.; Thalamus, J.; Westheim, A.; Dabrowski, M.; Gorski, J.; Korewicki, J.; Kuc, K.; Miekus, P.; Musial, W.; Niegowska, J.; Piotrowski, W.; Podolec, P.; Polonski, L.; Ponikowski, P.; Rynkiewicz, A.; Szelemej, R.; Trusz-Gluza, M.; Ujda, M.; Wojciechowski, D; Wysokinski, A.; Camacho, A.; Fonseca, C.; Monteiro, P.; Apetrei, E.; Bruckner, I.; Carasca, E.; Coman, I.; Datcu, M.; Dragulescu, S.; Ionescu, P.; Iordachescu-Petica, D.; Manitiu, I.; Popa, V.; Pop-Moldovan, A.; Radoi, M.; Stamate, S.; Tomescu, M.; Vita, I.; Aroutiounov, G.; Ballyuzek, M.; Bart, B.; Churina, S.; Glezer, M.; Goloshchekin, B.; Ivleva, A.; Kobalava, Z.; Kostenko, V.; Lopatin, Y.; Martynov, A.; Orlov, V.; Semernin, E.; Shogenov, Z.; Sidorenko, B.; Skvortsov, A.; Storzhakov, G.; Sulimov, V.; Talibov, O.; Tereshenko, S.; Tsyrline, V.; Zadionchenko, V.; Zateyshchikov, D.; Dzupina, A.; Hranai, M.; Kmec, J.; Micko, K.; Murin, J.; Pella, D.; Sojka, G.; Spisak, V.; Vahala, P.; Vinanska, D.; Badat, A.; Bayat, J.; Dawood, S.; Delport, E.; Ellis, G.; Garda, R.; Klug, E.; Mabin, T.; Naidoo, D.; Pretorius, M.; Ranjith, N.; Van Zyl, L.; Weich, H.; Anguita, M.; Berrazueta, J.; Bruguera i Cortada, J.; de Teresa, E.; Gómez Sánchez, M.; González Juanatey, J.; Gonzalez-Maqueda, I.; Jordana, R.; Lupon, J.; Manzano, L.; Pascual Figal, D.; Pulpón, L.; Recio, J.; Ridocci Soriano, F.; Rodríguez Lambert, J.; Roig Minguell, E.; Roig Minguell, E.; Romero, J.; Valdovinos, P.; Klintberg, L.; Kronvall, T.; Lycksell, M.; Morner, S.; Rydberg, E.; Swedberg, K.; Timberg, I.; Wikstrom, G.; Moccetti, T.4; Ashok, J.; Banerjee, P.; Carr-White, G.; Cleland, J.; Connolly, E.; Francis, M.; Greenbaum, R.; Kadr, H.; Lindsay, S.; McMurray, J.; Megarry, S.; Memon, A.; Murdoch, D.; Senior, R.; Squire, I.; Tan, L.; Witte, K.; Adams, K.; Adamson, P.; Adler, A.; Altschul, L.; Altschuller, A.; Amirani, H.; Anand, I.; Andreou, C.; Ansari, M.; Antonishen, M.; Banchs, H.; Banerjee, S.; Banish, D.; Bank, A.; Barbagelata, A.; Barnard, D.; Bellinger, R.; Benn, A.; Berk, M.; Berry, B.; Bethala, V.; Bilazarian, S.; Bisognano, J.; Bleyer, F.; Blum, M.; Boehmer, J.; Bouchard, A.; Boyle, A.; Bozkurt, B.; Brown, C.; Burlew, B.; Burnham, K.; Butler, J.; Call, J.; Cambier, P.; Cappola, T.; Carlson, R.; Chandler, B.; Chandra, R.; Chandraratna, P.; Chernick, R.; Colan, D.; Colfer, H.; Colucci, W.; Connelly, T.; Costantini, O.; Dadkhah, S.; Dauber, I.; Davis, J.; Davis, S.; Denning, S.; Drazner, M.; Dunlap, S.; Egbujiobi, L.; Elkayam, U.; Elliott, J.; El-Shahawy, M.; Essandoh, L.; Ewald, G.; Fang, J.; Farhoud, H.; Felker, G.; Fernandez, J.; Festin, R.; Fishbein, G.; Florea, V.; Flores, E.; Floro, J.; Gabris, M.; Garg, M.; Gatewood, R.; Geller, M.; Ghali, J.; Ghumman, W.; Gibbs, G.; Gillespie, E.; Gilmore, R.; Gogia, H.; Goldberg, L.; Gradus-Pizlo, I.; Grainger, T.; Gudmundsson, G.; Gunawardena, D.; Gupta, D.; Hack, T.; Hall, S.; Hamroff, G.; Hankins, S.; Hanna, M.; Hargrove, J.; Haught, W.; Hauptman, P.; Hazelrigg, M.; Herzog, C.; Heywood, J.; Hill, T.; Hilton, T.; Hirsch, H.; Hunter, J.; Ibrahim, H.; Imburgia, M.; Iteld, B.; Jackson, B.; Jaffrani, N.; Jain, D.; Jain, A.; James, M.; Jimenez, J.; Johnson, E.; Kale, P.; Kaneshige, A.; Kapadia, S.; Karia, D.; Karlsberg, R.; Katholi, R.; Kerut, E.; Khoury, W.; Kipperman, R.; Klapholz, M.; Kosinski, E.; Kozinn, M.; Kraus, D.; Krueger, S.; Krum, H.; Kumar, S.; Lader, E.; Lee, C.; Levy, W.; Lewis, E.; Light-McGroary, K.; Loh, I.; Lombardi, W.; Machado, C.; Maislos, F.; Mancini, D.; Markus, T.; Mather, P.; McCants, K.; McGrew, F.; McLaurin, B.; McMillan, E.; McNamara, D.; Meyer, T.; Meymandi, S.; Miller, A.; Minami, E.; Modi, M.; Mody, F.; Mohanty, P.; Moscoso, R.; Moskowitz, R.; Moustafa, M.; Mullen, M.; Naz, T.; Noonan, T.; O'Brien, T.; Oellerich, W.; Oren, R.; Pamboukian, S.; Pereira, N.; Pitt, W.; Porter, C.; Prabhu, S.; Promisloff, S.; Ratkovec, R.; Richardson, R.; Ross, A.; Saleh, N.; Saltzberg, M.; Sarkar, S.; Schmedtje, J.; Schneider, R.; Schuyler, G.; Shanes, J.; Sharma, A.; Siegel, C.; Siegel, R.; Silber, D.; Singh, V.; Singh, N.; Singh, J.; Sklar, J.; Small, R.; Smith, A.; Smith, E.; Smith, E.; Smull, D.; Sotolongo, R.; Staniloae, C.; Stapleton, D.; Steele, P.; Stehlik, J.; Stein, M.; Tang, W.; Thadani, U.; Torre-Amoine, G.; Trichon, B.; Tsai, C.; Tummala, R.; Van Bakel, A.; Vicari, R.; Vijay, N.; Vijayaraghavan, K.; Vittorio, T.; Vossler, M.; Wagoner, L.; Wallis, D.; Ward, N.; Widmer, M.; Wight, J.; Wilkins, C.; Williams, C.; Williams, G.; Winchester, M.; Winkel, E.; Wittmer, B.; Wood, D.; Wormer, D.; Wright, R.; Xu, Z.; Yasin, M.; Zolty, R.

    2013-01-01

    Aims This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. Methods and results Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L. Conclusion The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity. PMID:23329651

  11. Probing Neutrino Properties with Long-Baseline Neutrino Beams

    Energy Technology Data Exchange (ETDEWEB)

    Marino, Alysia [Univ. of Colorado, Boulder, CO (United States)

    2015-06-29

    This final report on an Early Career Award grant began in April 15, 2010 and concluded on April 14, 2015. Alysia Marino's research is focussed on making precise measurements of neutrino properties using intense accelerator-generated neutrino beams. As a part of this grant, she is collaborating on the Tokai-to-Kamioka (T2K) long-baseline neutrino experiment, currently taking data in Japan, and on the Deep Underground Neutrino Experiment (DUNE) design effort for a future Long-Baseline Neutrino Facility (LBNF) in the US. She is also a member of the NA61/SHINE particle production experiment at CERN, but as that effort is supported by other funds, it will not be discussed further here. T2K was designed to search for the disappearance of muon neutrinos (νμ) and the appearance of electron neutrinos (νe), using a beam of muon neutrino beam that travels 295 km across Japan towards the Super-Kamiokande detector. In 2011 T2K first reported indications of νe appearance, a previously unobserved mode of neutrino oscillations. In the past year, T2K has published a combined analysis of νμ disappearance and νe appearance, and began collecting taking data with a beam of anti-neutrinos, instead of neutrinos, to search for hints of violation of the CP symmetry of the universe. The proposed DUNE experiment has similar physics goals to T2K, but will be much more sensitive due to its more massive detectors and new higher-intensity neutrino beam. This effort will be very high-priority particle physics project in the US over the next decade.

  12. Automated baseline change detection -- Phases 1 and 2. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Byler, E.

    1997-10-31

    The primary objective of this project is to apply robotic and optical sensor technology to the operational inspection of mixed toxic and radioactive waste stored in barrels, using Automated Baseline Change Detection (ABCD), based on image subtraction. Absolute change detection is based on detecting any visible physical changes, regardless of cause, between a current inspection image of a barrel and an archived baseline image of the same barrel. Thus, in addition to rust, the ABCD system can also detect corrosion, leaks, dents, and bulges. The ABCD approach and method rely on precise camera positioning and repositioning relative to the barrel and on feature recognition in images. The ABCD image processing software was installed on a robotic vehicle developed under a related DOE/FETC contract DE-AC21-92MC29112 Intelligent Mobile Sensor System (IMSS) and integrated with the electronics and software. This vehicle was designed especially to navigate in DOE Waste Storage Facilities. Initial system testing was performed at Fernald in June 1996. After some further development and more extensive integration the prototype integrated system was installed and tested at the Radioactive Waste Management Facility (RWMC) at INEEL beginning in April 1997 through the present (November 1997). The integrated system, composed of ABCD imaging software and IMSS mobility base, is called MISS EVE (Mobile Intelligent Sensor System--Environmental Validation Expert). Evaluation of the integrated system in RWMC Building 628, containing approximately 10,000 drums, demonstrated an easy to use system with the ability to properly navigate through the facility, image all the defined drums, and process the results into a report delivered to the operator on a GUI interface and on hard copy. Further work is needed to make the brassboard system more operationally robust.

  13. Probing Neutrino Properties with Long-Baseline Neutrino Beams

    Energy Technology Data Exchange (ETDEWEB)

    Marino, Alysia [Univ. of Colorado, Boulder, CO (United States)

    2015-06-29

    This is nal report on an Early Career Award grant began in April 15, 2010 and concluded on April 14, 2015. Alysia Marino's research is fo- cussed on making precise measurements of neutrino properties using in- tense accelerator-generated neutrino beams. As a part of this grant, she is collaborating on the Tokai-to-Kamioka (T2K) long-baseline neutrino exper- iment [6], currently taking data in Japan, and on the Deep Underground Neutrino Experiment (DUNE) design e ort for a future Long-Baseline Neu- trino Facility (LBNF) in the US.1 She is also a member of the NA61/SHINE particle production experiment at CERN, but as that e ort is supported by other funds, it will not be discussed further here. T2K was designed to search for the disappearance of muon neutrinos ( ) and the appearance of electron neutrinos ( e), using a beam of muon neu- trino beam that travels 295 km across Japan towards the Super-Kamiokande detector. In 2011 T2K rst reported indications of e appearance [2], a pre- viously unobserved mode of neutrino oscillations. In the past year, T2K has published a combined analysis of disappearance and e appearance [1], and began collecting taking data with a beam of anti-neutrinos, instead of neutrinos, to search for hints of violation of the CP symmetry of the uni- verse. The proposed DUNE experiment has similar physics goals to T2K, but will be much more sensitive due to its more massive detectors and new higher-intensity neutrino beam. This e ort will be very high-priority particle physics project in the US over the next decade.

  14. Baseline Gas Turbine Development Program seventh quarterly progress report

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, F.W.

    1974-07-30

    Progress is reported for a program to demonstrate by 1976 an experimental gas turbine powered automobile which meets the 1976 Federal Emissions Standards, has significantly improved fuel economy, and is competitive in performance, reliability, and potential manufacturing cost with the conventional piston engine powered, standard size American automobile. All of the baseline vehicles are now operational and are performing Program tests. Vehicle tests completed in this quarter include noise reduction, heater, air conditioning, and underhood temperature evaluations. Testing was completed on the original endurance engine. Test cell evaluation of the government furnished combustor (Solar) has commenced. Vendor A and Vendor B ceramic regenerator cores were rig tested with an improved elastomeric drive. Vendor A cores with the elastomeric drive are being engine tested. Ceramic regenerator seal wear test rig results are showing promise of achieving a low friction, non-nickel-oxide rubbing surface. The first preprototype integrated control system was delivered and placed in operation on a baseline engine in a test cell. Six ribbed compressor turbine wheels made of IN 792/Hf by the AiResearch Airefrac process were received. Rig testing of the variable inlet guide Vanes was completed and engine testing initiated. Vehicle evaluations of the torque converter lock-up were completed . Specifications for the Upgraded Engine aerodymanic components were made. A subcontract is currently being arranged with Mechanical Technology Inc. (MTI) for design and development of the upgraded engine gas generator bearings and shaft system. An initial feasibility study for gas bearings was completed. Analytical design of the upgraded engine power turbine reduction gears and bearings has commenced. Engine and vehicle accessory drive studies for the upgraded engine are well underway.

  15. Baseline Gas Turbine Development Program eighth quarterly progress report

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, C.E.

    1974-10-31

    Progress is reported for a program to demonstrate by 1976 an experimental gas turbine powered automobile which meets the 1978 Federal Emissions Standards, has significantly improved fuel economy, and is competitive in performance, reliability, and potential manufacturing cost with the conventional piston engine powered, standard size American automobile. Major preparations for engine heat balance tests by NASA were completed. EPA laboratories completed Baseline vehicle emissions, noise, and odor tests. Assembly of the program endurance engine is nearing completion. Test cell evaluation of the government furnished combustor (Solar) verified steady state emissions to be extremely low. Initial engine tests of Vendor A ceramic regenerator cores with an elastomeric drive verified performance predictions. Efforts towards developing a non-nickel oxide regenerator seal show extreme sensitivity to porosity differences between cores of different suppliers. All three preprototype integrated control systems were built. Modifications are being worked out to achieve a stable low speed operation. Two prototype compressor turbine wheels made from the reuseable pattern process are being inspected and processed for testing. The engine housing modified for operation at higher cycle temperatures and pressures was received. The baseline engine converted to free rotor is completing test cell check out. The modified vehicle is ready for engine installation. The upgraded engine characterization was updated to include the latest information on V.I.G.V., rotors, and bearings. The upgraded engine housing is being modeled physically and analytically for design and stress studies. An accessory drive system for the upgraded engine was selected, and a final layout is in process.

  16. Predictive modeling of respiratory tumor motion for real-time prediction of baseline shifts

    Science.gov (United States)

    Balasubramanian, A.; Shamsuddin, R.; Prabhakaran, B.; Sawant, A.

    2017-03-01

    prediction performance. The ability to predict a baseline shift with a sufficient look-ahead window will enable clinical systems or even human users to hold the treatment beam in such situations, thereby reducing the probability of serious geometric and dosimetric errors.

  17. Gcg-XTEN: an improved glucagon capable of preventing hypoglycemia without increasing baseline blood glucose.

    Directory of Open Access Journals (Sweden)

    Nathan C Geething

    Full Text Available OBJECTIVE: While the majority of current diabetes treatments focus on reducing blood glucose levels, hypoglycemia represents a significant risk associated with insulin treatment. Glucagon plays a major regulatory role in controlling hypoglycemia in vivo, but its short half-life and hyperglycemic effects prevent its therapeutic use for non-acute applications. The goal of this study was to identify a modified form of glucagon suitable for prophylactic treatment of hypoglycemia without increasing baseline blood glucose levels. METHODOLOGY/PRINCIPAL FINDINGS: Through application of the XTEN technology, we report the construction of a glucagon fusion protein with an extended exposure profile (Gcg-XTEN. The in vivo half-life of the construct was tuned to support nightly dosing through design and testing in cynomolgus monkeys. Efficacy of the construct was assessed in beagle dogs using an insulin challenge to induce hypoglycemia. Dose ranging of Gcg-XTEN in fasted beagle dogs demonstrated that the compound was biologically active with a pharmacodynamic profile consistent with the designed half-life. Prophylactic administration of 0.6 nmol/kg Gcg-XTEN to dogs conferred resistance to a hypoglycemic challenge at 6 hours post-dose without affecting baseline blood glucose levels. Consistent with the designed pharmacokinetic profile, hypoglycemia resistance was not observed at 12 hours post-dose. Importantly, the solubility and stability of the glucagon peptide were also significantly improved by fusion to XTEN. CONCLUSIONS/SIGNIFICANCE: The data show that Gcg-XTEN is effective in preventing hypoglycemia without the associated hyperglycemia expected for unmodified glucagon. While the plasma clearance of this Gcg-XTEN has been optimized for overnight dosing, specifically for the treatment of nocturnal hypoglycemia, constructs with significantly longer exposure profiles are feasible. Such constructs may have multiple applications such as allowing for more

  18. GLoBES: General Long Baseline Experiment Simulator

    Science.gov (United States)

    Huber, Patrick; Kopp, Joachim; Lindner, Manfred; Rolinec, Mark; Winter, Walter

    2007-09-01

    GLoBES (General Long Baseline Experiment Simulator) is a flexible software package to simulate neutrino oscillation long baseline and reactor experiments. On the one hand, it contains a comprehensive abstract experiment definition language (AEDL), which allows to describe most classes of long baseline experiments at an abstract level. On the other hand, it provides a C-library to process the experiment information in order to obtain oscillation probabilities, rate vectors, and Δχ-values. Currently, GLoBES is available for GNU/Linux. Since the source code is included, the port to other operating systems is in principle possible. GLoBES is an open source code that has previously been described in Computer Physics Communications 167 (2005) 195 and in Ref. [7]). The source code and a comprehensive User Manual for GLoBES v3.0.8 is now available from the CPC Program Library as described in the Program Summary below. The home of GLobES is http://www.mpi-hd.mpg.de/~globes/. Program summaryProgram title: GLoBES version 3.0.8 Catalogue identifier: ADZI_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADZI_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 145 295 No. of bytes in distributed program, including test data, etc.: 1 811 892 Distribution format: tar.gz Programming language: C Computer: GLoBES builds and installs on 32bit and 64bit Linux systems Operating system: 32bit or 64bit Linux RAM: Typically a few MBs Classification: 11.1, 11.7, 11.10 External routines: GSL—The GNU Scientific Library, www.gnu.org/software/gsl/ Nature of problem: Neutrino oscillations are now established as the leading flavor transition mechanism for neutrinos. In a long history of many experiments, see, e.g., [1], two oscillation frequencies have been identified: The fast atmospheric

  19. 75 FR 38802 - DCP Raptor Pipeline, LLC; Notice of Baseline Filing

    Science.gov (United States)

    2010-07-06

    ...] DCP Raptor Pipeline, LLC; Notice of Baseline Filing June 28, 2010. Take notice that on June 22, 2010, DCP Raptor Pipeline, LLC submitted a baseline filing of its Statement of Operating Conditions...

  20. Baseline (1961-1990) average air temperature (degree C) for Alaska and Western Canada.

    Data.gov (United States)

    Arctic Landscape Conservation Cooperative — Baseline (1961-1990) average air temperature (degree C) for Alaska and Western Canada. Baseline results for 1961-1990 are derived from Climate Research Unit (CRU)...

  1. Baseline (1961-1990) average air temperature (degree F) for Alaska and Western Canada.

    Data.gov (United States)

    Arctic Landscape Conservation Cooperative — Baseline (1961-1990) average air temperature (degree F) for Alaska and Western Canada. Baseline results for 1961-1990 are derived from Climate Research Unit (CRU) TS...

  2. Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control

    Directory of Open Access Journals (Sweden)

    Bays HE

    2015-02-01

    Full Text Available Harold E Bays,1 Eliot A Brinton,2 Joseph Triscari,3 Erluo Chen,3 Darbie Maccubbin,3 Alexandra A MacLean,3 Kendra L Gibson,3 Rae Ann Ruck,3 Amy O Johnson-Levonas,3 Edward A O’Neill,3 Yale B Mitchel3 1Louisville Metabolic & Atherosclerosis Research Center (L-MARC, Louisville, KY, USA; 2Utah Foundation for Biomedical Research, Salt Lake City, UT, USA; 3Merck & Co, Inc., Whitehouse Station, NJ, USA Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM may alter lipid levels and may alter the efficacy of lipid-modifying agents. Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant