Decreased Prevalence of Plasmodium Falciparum Resistance Markers to Amodiaquine Despite its wide Scale use as ACT Partner Drug in Zanzibar.

Zanzibar has recently undergone a rapid decline in Plasmodium falciparum transmission following combined malaria control interventions with artemisinin-based combination therapy (ACT) and integrated vector control. Artesunate-amodiaquine (ASAQ) was implemented as first-line treatment for uncomplicated P. falciparum malaria in Zanzibar in 2003. Resistance to amodiaquine has been associated with the single nucleotide polymorphism (SNP) alleles pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y. An accumulation of these SNP alleles in the parasite population over time might threaten ASAQ efficacy.The aim of this study was to assess whether prolonged use of ASAQ as first-line anti-malarial treatment selects for P. falciparum SNPs associated with resistance to the ACT partner drug amodiaquine. The individual as well as the combined SNP allele prevalence were compared in pre-treatment blood samples from patients with uncomplicated P. falciparum malaria enrolled in clinical trials conducted just prior to the introduction of ASAQ in 2002-2003 (n = 208) and seven years after wide scale use of ASAQ in 2010 (n = 122). There was a statistically significant decrease of pfcrt 76T (96-63%), pfmdr1 86Y (75-52%), 184Y (83-72%), 1246Y (28-16%) and the most common haplotypes pfcrt/pfmdr1 TYYD (46-26%) and TYYY (17-8%), while an increase of pfcrt/pfmdr1 KNFD (0.4-14%) and KNYD (1-12%). This is the first observation of a decreased prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y in an African setting after several years of extensive ASAQ use as first-line treatment for uncomplicated malaria. This may support sustained efficacy of ASAQ on Zanzibar, although it was unexpected considering that all these SNPs have previously been associated with amodiaquine resistance. The underlying factors of these results are unclear. Genetic dilution by imported P. falciparum parasites from mainland Tanzania, a de-selection by artesunate per se and/or an associated fitness cost might represent contributing factors. More detailed studies on temporal trends of molecular markers associated with amodiaquine resistance are required to improve the understanding of this observation

CYP2C8 status of patients with malaria influences selection of Plasmodium falciparum pfmdr1 Alleles after Amodiaquine-Artesunate treatment

info:eu-repo/semantics/publishedVersio

Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine

Cell phone-supported cognitive behavioural therapy for anxiety disorders: a protocol for effectiveness studies in frontline settings

The resulting protocol (NCT01205191 at clinicaltrials.gov) for use in frontline clinical practice in which effectiveness, adherence, and the role of the therapists are analyzed, provides evidence for what are truly valuable cell phone-supported CBT treatments and guidance for the broader introduction of CBT in health services.Original Publication:Joakim Ekberg, Toomas Timpka, Magnus Bång, Anders Fröberg, Karin Halje and Henrik Eriksson, Cell phone-supported cognitive behavioural therapy for anxiety disorders: a protocol for effectiveness studies in frontline settings., 2011, BMC medical research methodology, (11), 3.http://dx.doi.org/10.1186/1471-2288-11-3Copyright: BioMed Centralhttp://www.biomedcentral.com

Efficient Simulation and Optimal Control for Vehicle Propulsion

Efficient drive cycle simulation of longitudinal vehicle propulsion models is an important aid for design and analysis of power trains. Tools on the market today mainly use two different methods for such simulations, forward dynamic or quasi-static inverse simulation. Here known theory for stable inversion of non linear systems is used in order to combine the fast simulation times of the quasi-static inverse simulation with the ability of including transient dynamics as in the forward dynamic simulation. The stable inversion technique with a new implicit driver model together forms a new concept, inverse dynamic simulation. This technique is demonstrated feasible for vehicle propulsion simulation and specifically on three powertrain applications that include important dynamics that can not be handled using quasi-static inverse simulation. The extensions are engine dynamics, drive line dynamics, and gas flow dynamics for diesel engines, which also are selected to represent important properties such as zero dynamics, resonances, and non-minimum phase systems. It is shown that inverse dynamic simulation is easy to set up, gives short simulation times, and gives consistent results for design space exploration. This make

Vår passion, nyproduktion! : Hur kan nyproduktion av hyresrätter stimuleras?

Sedan två år tillbaka byggs det för fösta gången i Sverige fler bostadsrätter än hyresrätter. Enligt resultatet av Boverkets årliga bostadsmarknadsenkät 2008 råder det bostadsbrist i 50 % av landets kommuner. Trots bostadsbrist i storstadsregioner är nyproduktionen anmärkningsvärt låg. Inte sedan 1920- och 1930-talet har nyproduktionen varit så låg i Sverige.   Hyresrätten är viktig som upplåtelseform. Den tillåter ett flexibelt boende som möjliggör effektiv förflyttning av arbetskraft, ett första boende för unga och ofta enda alternativet för låginkomsttagare.   En anledning till att det produceras så få hyresrätter i dagsläget är att de statliga investerings- och räntebidragen försvann 2006. Höga produktionskostnader har gjort det allt svårare att få lönsamhet i nyproduktion. Det har förts en högljudd infekterad debatt angående det hyresreglerande bruksvärdessystemet. Motståndarna till bruksvärdessystemet vill införa marknadshyror och menar att det skulle förbättra dagens bostadssituation. Andra röster menar att ett återinförande av statliga subventioner är rätt väg att gå för att stimulera nyproduktion av hyresrätter. Andra säger att det krävs en förändring och effektivisering av själva byggprocessen och därigenom åstadkomma sänkta produktionskostnader. Energipriserna stiger och förväntas bli allt högre i framtiden. Därför kan det löna sig att bygga energieffektivt och sänka sina driftkostnader på hyreshus.   Vi vill med denna uppsats undersöka vilka möjligheter det finns för att stimulera nyproduktion av hyresrätter i Sverige. Vi valde att undersöka tre mycket olika fastighetsmarknader för att kunna bilda oss en uppfattning av problemen på olika marknader. Förutom att intervjua nyckelpersoner på de olika marknaderna utförde vi en marknadssimulering samt deltog i ett bostadsseminarium.   Vårt resultat av våra undersökningar visar att problemen vid nyproduktion ser mycket olika ut på de tre marknaderna. Dock finns ett behov av hyresrätter/bostäder på samtliga marknader. Vidare har vi i korthet kunnat dra följande slutsatser.   Statliga subventioner är ingen fungerande långsiktig lösning på problemet. De tenderar att enbart höja produktionskostnaden. Marknadshyror är ingen generell lösning på problemet och skulle förmodligen bara öka nyproduktionen på mycket attraktiva marknader. Omfattande detaljplaner tvingar nyproduktion att se ut på ett visst sätt, som inte alltid är kostnadseffektivt. Vidare krävs en effektivare planprocess. Att bygga med lägre standard resulterar inte i någon nämnvärd besparing och är svårt att administrera. Att bygga energieffektivare hyreshus medför en ökad lönsamhet i ett längre perspektiv på samtliga marknader.

Development of Look-Ahead Controller Concepts for a Wheel Loader Application

This paper presents two conceptual methods, based on dynamic programming, for one-step look-ahead control of a Continuously Variable Transmission (CVT) in a wheel loader. The first method developed, designated Stochastic Dynamic Programming (SDP), uses a statistical load prediction and stochastic dynamic programming for minimizing fuel use. The second method developed, designated Free-Time Dynamic Programming (FTDP), has vehicle speed as a state and introduces a fixed 0.1 s delay in the bucket controls in a combined minimization of fuel and time. The methods are evaluated using a set of 34 measured loading cycles, used in a ‘leave one out’ manner. The evaluation shows that the SDP method requires about 1/10th of the computational effort of FTDP and has a more transparent impact of differences in the cycle prediction. The FTDP method, on the other hand, shows a 10% lower fuel consumption, which is close to the actual optimum, at the same cycle times, and is able to complete a much larger part of the evaluation cycles