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Article: Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali[Show abstract] [Hide abstract]
ABSTRACT: Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading in that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) sin the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be associated with artemisinin resistance in vivo and in vitro. The prevalence and role of K13-propeller mutations are poorly known in sub-Saharan Africa. K13-propeller mutations were genotyped by direct sequencing of nested polymerase chain reaction (PCR) amplicons from dried blood spots of pre-treatment falciparum malaria infections collected before and after the use of artemisinin-based combination therapy (ACT) as first-line therapy in Mali. Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections. Parasite clearance time was comparable between infections with non-synonymous K13-propeller mutations and infections with the reference allele. These findings suggest that K13-propeller mutations are present in artemisinin-sensitive parasites and that they preceded the wide use of ACTs in Mali. © The American Society of Tropical Medicine and Hygiene.The American journal of tropical medicine and hygiene 04/2015; 92(6). DOI:10.4269/ajtmh.14-0605 · 2.74 Impact Factor
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ABSTRACT: Amodiaquine (AQ) is a 4-aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short-lived quinine-imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar's population regarding the appearance of adverse effects.Tropical Medicine & International Health 05/2012; 17(7):854-7. DOI:10.1111/j.1365-3156.2012.03011.x · 2.30 Impact Factor
Article: Drug resistance associated genetic polymorphisms in Plasmodium falciparum and Plasmodium vivax collected in Honduras, Central America[Show abstract] [Hide abstract]
ABSTRACT: In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras. Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospitals, two health centres and one regional laboratory during 2009. Single nucleotide polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and in P. vivax multidrug resistance 1 (pvmdr1) and dihydrofolate reductase (pvdhfr) genes were detected using PCR based methods. Thirty seven P. falciparum and 64 P. vivax samples were collected. All P. falciparum infections acquired in Honduras carried pfcrt, pfmdr1, pfdhps and pfdhfr alleles associated with chloroquine, amodiaquine and sulphadoxine-pyrimethamine sensitivity only. One patient with parasites acquired on a Pacific Island had pfcrt 76 T and pfmdr1 86Y alleles. That patient and a patient infected in West Africa had pfdhfr 51I, 59 R and 108 N alleles. Pvmdr1 976 F was found in 7/37 and two copies of pvmdr1 were found in 1/37 samples. Pvdhfr 57 L + 58 R was observed in 2/57 samples. The results indicate that P. falciparum from Honduras remain sensitive to chloroquine and sulphadoxine-pyrimethamine. This suggests that chloroquine and sulphadoxine-pyrimethamine should be efficacious for treatment of uncomplicated P. falciparum malaria, supporting current national treatment guidelines. However, genetic polymorphisms associated with chloroquine and sulphadoxine-pyrimethamine tolerance were detected in local P. vivax and imported P. falciparum infections. Continuous monitoring of the prevalence of drug resistant/tolerant P. falciparum and P. vivax is therefore essential also in Honduras.Malaria Journal 12/2011; 10:376. DOI:10.1186/1475-2875-10-376 · 3.49 Impact Factor
Article: Reductions in malaria and anaemia case and death burden at hospitals following scale-up of malaria control in Zanzibar, 1999-2008[Show abstract] [Hide abstract]
ABSTRACT: In Zanzibar, the Ministry of Health and partners accelerated malaria control from September 2003 onwards. The impact of the scale-up of insecticide-treated nets (ITN), indoor-residual spraying (IRS) and artemisinin-combination therapy (ACT) combined on malaria burden was assessed at six out of seven in-patient health facilities. Numbers of outpatient and inpatient cases and deaths were compared between 2008 and the pre-intervention period 1999-2003. Reductions were estimated by segmented log-linear regression, adjusting the effect size for time trends during the pre-intervention period. In 2008, for all age groups combined, malaria deaths had fallen by an estimated 90% (95% confidence interval 55-98%)(p < 0.025), malaria in-patient cases by 78% (48-90%), and parasitologically-confirmed malaria out-patient cases by 99.5% (92-99.9%). Anaemia in-patient cases decreased by 87% (57-96%); anaemia deaths and out-patient cases declined without reaching statistical significance due to small numbers. Reductions were similar for children under-five and older ages. Among under-fives, the proportion of all-cause deaths due to malaria fell from 46% in 1999-2003 to 12% in 2008 (p < 0.01) and that for anaemia from 26% to 4% (p < 0.01). Cases and deaths due to other causes fluctuated or increased over 1999-2008, without consistent difference in the trend before and after 2003. Scaling-up effective malaria interventions reduced malaria-related burden at health facilities by over 75% within 5 years. In high-malaria settings, intensified malaria control can substantially contribute to reaching the Millennium Development Goal 4 target of reducing under-five mortality by two-thirds between 1990 and 2015.Malaria Journal 02/2011; 10(1):46. DOI:10.1186/1475-2875-10-46 · 3.49 Impact Factor
Conference Paper: Molecular genotypes and clearance of different P. falciparum sub populations in children treated with ACTTROPICAL MEDICINE & INTERNATIONAL HEALTH; 01/2011
Article: Impact of training in clinical and microscopy diagnosis of childhood malaria on antimalarial drug prescription and health outcome at primary health care level in Tanzania: A randomized controlled trial[Show abstract] [Hide abstract]
ABSTRACT: Prescribing antimalarial medicines based on parasite confirmed diagnosis of malaria is critical to rational drug use and optimal outcome of febrile illness. The impact of microscopy-based versus clinical-based diagnosis of childhood malaria was assessed at primary health care (PHC) facilities using a cluster randomized controlled training intervention trial. Sixteen PHC facilities in rural Tanzania were randomly allocated to training of health staff in clinical algorithm plus microscopy (Arm-I, n = 5) or clinical algorithm only (Arm-II, n = 5) or no training (Arm-III, n = 6). Febrile under-five children presenting at these facilities were assessed, treated and scheduled for follow up visit after 7 days. Blood smears on day 0 were only done in Arm-I but on Day 7 in all arms. Primary outcome was antimalarial drug prescription. Other outcomes included antibiotic prescription and health outcome. Multilevel regression models were applied with PHC as level of clustering to compare outcomes in the three study arms. A total of 973, 1,058 and 1,100 children were enrolled in arms I, II and III, respectively, during the study period. Antimalarial prescriptions were significantly reduced in Arm-I (61.3%) compared to Arms-II (95.3%) and III (99.5%) (both P < 0.001), whereas antibiotic prescriptions did not vary significantly between the arms (49.9%, 54.8% and 34.2%, respectively). In Arm-I, 99.1% of children with positive blood smear readings received antimalarial prescriptions and so did 11.3% of children with negative readings. Those with positive readings were less likely to be prescribed antibiotics than those with negative (relative risk = 0.66, 95% confidence interval: 0.55, 0.72). On day 7 follow-up, more children reported symptoms in Arm-I compared to Arm-III, but fewer children had malaria parasitaemia (p = 0.049). The overall sensitivity of microscopy reading at PHC compared to reference level was 74.5% and the specificity was 59.0% but both varied widely between PHCs. Microscopy based diagnosis of malaria at PHC facilities reduces prescription of antimalarial drugs, and appears to improve appropriate management of non-malaria fevers, but major variation in accuracy of the microscopy readings was found. Lack of qualified laboratory technicians at PHC facilities and the relatively short training period may have contributed to the shortcomings. This study is registered at Clinicaltrials.gov with the identifier NCT00687895.Malaria Journal 10/2008; 7(1):199. DOI:10.1186/1475-2875-7-199 · 3.49 Impact Factor
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ABSTRACT: The indications for prescribing malaria chemoprophylaxis lack a solid evidence base that results in subjectivity and wide variation of practice across countries and among professionals. European experts in travel medicine, who are members of TropNetEurop, participated in a survey conducted using the Delphi method. This technique aims at evaluating and developing a consensus through iterations of questionnaires, controlled feedback, and statistical group responses. A first questionnaire, including questions about controversial issues in prescribing malaria prophylaxis, required responses on a visual scale between 1 and 10. The questionnaire included issues on problematic prescribing, characteristics of drugs, relevance of geography, and importance of insect bite prevention. The repeat questionnaire with the group response from the first round revealed an increasing consensus on most issues. A second survey considered 14 practical scenarios (including two internal standards) and investigated preferred choice of prophylaxis. A significant consensus was noted in 8 of 14 scenarios, which did not increase after a second round. The analysis revealed a wide variation in prescribing choices with preferences grouped by region of practice, and a greater willingness to prescribe in northern and southern Europe than in central Europe. The second round showed a 9.5% change of opinion. The study shows that improving the evidence base on efficacy and tolerability and risk of malaria for prescribing chemoprophylaxis is needed as is further discussion across Europe to achieve harmonization of prescribing practice.Journal of Travel Medicine 09/2008; 15(5):294-301. DOI:10.1111/j.1708-8305.2008.00226.x · 1.53 Impact Factor
Conference Paper: Pfmdr1 gene expression during all Plasmodium falciparum erythrocyte cycle with mefloquine pressure.INTERNATIONAL JOURNAL FOR PARASITOLOGY; 01/2008
Conference Paper: The sarco/endoplasmic reticulum Ca2+-ATPase orthologue of Plasmodium falciparum (PfATP6) harbours high SNP diversity.INTERNATIONAL JOURNAL FOR PARASITOLOGY; 01/2008
Article: Effect of artesunate plus sulfadoxine-pyrimethamine on haematological recovery and anaemia, in Kenyan children with uncomplicated, Plasmodium falciparum malaria[Show abstract] [Hide abstract]
ABSTRACT: Malaria-associated anaemia is a major public-health problem. Although the treatment of uncomplicated, Plasmodium falciparum malaria aims to clear the parasites, relieve the symptoms and permit haematological recovery, data on the impact of antimalarial treatment on haematological recovery are few. Haematological recovery and the prevalence of anaemia were therefore evaluated in 600 Kenyan children with uncomplicated malaria who were randomly assigned to one of three treatment groups. The children were given sulfadoxine-pyrimethamine (SP) on day 0, SP plus artesunate on day 0 (AS1), or SP on day 0 and artesunate on each of days 0-2 (AS3). Haemoglobin (Hb) concentrations were measured on days 0, 7, 14, 21 and 28, with haematological recovery defined as a day-28 Hb concentration of at least 11 g/dl. Only 96 (18%) of the 543 children who were anaemic (i.e. with <11.0 g Hb/dl) at enrolment achieved haematological recovery. The prevalence of anaemia fell from 91% on day 0 to 74% (252/340) by day 28 (P=0.065). Compared with SP alone, neither artesunate regimen resulted in higher Hb concentrations on day 28 (with means of 10.2, 9.9 and 10.2 g/dl for AS3, AS1 and SP, respectively; P=0.254), a higher frequency of haematological recovery (19%, 14% and 20% for AS3, AS1 and SP, respectively; P=0.301) or a greater reduction in the prevalence of anaemia (prevalences in the AS3, AS1 and SP arms falling from 90%, 89% and 93%, respectively, on day 0, to corresponding values of 71%, 82% and 69% on day 28; P=0.40). In fact, between days 0 and 7, the children in the AS3 arm showed a larger drop in mean Hb than the children in the other two treatment arms. In general, haematological recovery was most likely in older children who had mild anaemia at presentation and were parasitologically cured. Overall, the frequencies of haematological recovery were modest and not influenced by the artesunate treatments. Other factors contributing to anaemia need to be explored more fully.Annals of Tropical Medicine and Parasitology 07/2007; 101(4):281-95. DOI:10.1179/136485907X176337 · 1.20 Impact Factor
Article: Influence of consecutive-day blood sampling on polymerase chain reaction-adjusted parasitological cure rates in an antimalarial-drug trial conducted in Tanzania.[Show abstract] [Hide abstract]
ABSTRACT: We assessed the influence that consecutive-day blood sampling, compared with single-day blood sampling, had on polymerase chain reaction (PCR)-adjusted parasitological cure after stepwise genotyping of merozoite surface proteins 2 (msp2) and 1 (msp1) in 106 children in Tanzania who had uncomplicated falciparum malaria treated with either sulfadoxine-pyrimethamine or artemether-lumefantrine; 78 of these children developed recurrent parasitemia during the 42-day follow-up period. Initial msp2 genotyping identified 27 and 33 recrudescences by use of single- and consecutive-day sampling, respectively; in subsequent msp1 genotyping, 17 and 21 of these episodes, respectively, were still classified as recrudescences; these results indicate a similar sensitivity of the standard single-day PCR protocol--that is, 82% (27/33) and 81% (17/21), in both genotyping steps. Interpretation of PCR-adjusted results will significantly depend on methodology.The Journal of Infectious Diseases 03/2007; 195(4):597-601. DOI:10.1086/510910 · 5.78 Impact Factor
Conference Paper: Polymorphisms of drug metabolising, nuclear receptor and drug transport genes among malaria patients in ZanzibarTROPICAL MEDICINE & INTERNATIONAL HEALTH; 01/2007
Article: Algorithm for the diagnosis of anaemia without laboratory facilities among small children in a malaria endemic area of rural Tanzania.[Show abstract] [Hide abstract]
ABSTRACT: Anaemia among small children in tropical Africa is common and often caused by infection with Plasmodium falciparum. The diagnosis of anaemia is difficult without a laboratory estimation of haemoglobin. The aim of this study was to examine if clinical findings related to malaria and anaemia would help to detect moderate and/or severe anaemia in children in rural Tanzania. Children between 6 and 36 months were examined by health workers in an Out Patient Department (OPD) to detect severe anaemia (packed cell volume, PCV< or =20%) and in a cross sectional survey at village level to identify moderate anaemia (PCV 21-25%). History of recent fever and treatments was recorded and a clinical examination was performed. In the survey, comparison of 65 moderately anaemic children with 373 mild/non anaemic children revealed no differences in history of fever or in the clinical examination. In the OPD comparison of 100 severely anaemic children with 116 non-severely anaemic control children revealed that pallor, respiratory rate, number of fever days last week, deteriorated general condition, heart rate, age, splenomegaly, low body weight and elevated body temperature were all indicators of severe 'anaemia, only pallor, respiratory rate, fever days and palpable spleen however, remained associated with severe anaemia in multiple regression analysis. The combination of any pallor and either respiratory rate >55/min or fever >3 days, could predict severe anaemia with a sensitivity of 96% and a specificity of 71%. This was better than the currently recommended signs of severe pallor or an approximation of the Integrated Management of Childhood Illness (IMCI) criteria's for referral of children. At primary health care level detection of severe anaemia can be improved by information about fever duration and determination of respiratory rate in children with pallor.Acta Tropica 10/2006; 99(2-3):119-25. DOI:10.1016/j.actatropica.2005.12.011 · 2.52 Impact Factor
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ABSTRACT: Anaemia is a major complication of Plasmodium falciparum malaria among small children in sub-Saharan Africa. We studied the performance of the Integrated Management of Childhood Illness (IMCI) recommended assessment of no/some/severe pallor as predictor of anaemia in health surveys at community level and in clinical practice in an out patient department (OPD) and in a hospital ward in rural Tanzania. The study was undertaken among 6-36 months old children. Pallor was evaluated as a combined assessment of conjunctiva, tongue and palms and categorised as no, some or severe pallor. Packed cell volume (PCV) was measured and related to pallor. A total of 740 examinations were performed at village, OPD and in the hospital ward. The prevalences of severe pallor were 0%, 1.5% and 7% respectively. The prevalences of any pallor were 14%, 41% and 86%. The prevalences of severe anaemia (PCV<21%) were 1%, 5% and 81% and of any anaemia (PCV<33%) 68%, 73% and 98%. Severe pallor could not detect severe anaemia. The sensitivities were only 0%, 0% and 8%. The sensitivities of any pallor to detect severe anaemia were however 86% and 98% for children at the health care facility level, but still of relatively poor predictive values since the specificities were only 61% and 68%. Division of pallor into some or severe degrees was of no use at any health care level. The identification of any pallor was of no use at village level, but it may possibly be of some value as a screening test for severe anaemia at health care facilities, if additional assessment is included in view of the low specificity and positive predictive value of the finding.Acta Tropica 10/2006; 99(2-3):113-8. DOI:10.1016/j.actatropica.2005.12.010 · 2.52 Impact Factor
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ABSTRACT: The determination of the prevalence of the CYP2C8 main alleles in a typical set of malaria patients in Zanzibar, as these patients represent a typical population exposed to amodiaquine, an antimalarial mainly metabolized by CYP2C8. Also, to determine for the first time the frequencies of CYP2C8 alleles in native African populations. Polymerase chain reaction-restriction fragment polymorphism for the identification of CYP2C8*1, CYP2C8*2, CYP2C8*3 and CYP2C8*4 on a random population of 165 unrelated malaria patients. The allele frequencies found were: CYP2C8*1 (wild type, 83.4%), CYP2C8*2 (13.9%), CYP2C8*3 (2.1%) and CYP2C8*4 (0.6%). In terms of genotypes, 70.4% of the patients showed the CYP2C8*1/ CYP2C8*1 genotypes, while heterozygous between the wild type and other minor alleles were seen in 26.0%. Finally, 3.6% of the patients were homozygous for slow metabolizer alleles. The frequencies observed are equivalent to those documented for African-Americans. CYP2C8 non-wild type alleles have a significant prevalence in the East African population studied. The consequent frequency of 3.6% of patients homozygous for slow metabolizer alleles represent a significant fraction of the population potentially in higher risk of adverse effects due to a less efficient metabolism of amodiaquine. As approximately 10(6) first-line treatments are currently performed in Zanzibar per year, this represents a non-negligible absolute number of amodiaquine exposures. This information constitutes a background for the pharmacovigilance programs presently being employed in Zanzibar.European Journal of Clinical Pharmacology 04/2005; 61(1):15-8. DOI:10.1007/s00228-004-0871-8 · 2.70 Impact Factor
Article: High prevalence of double Plasmodium falciparum dhfr mutations at codons 108 and 59 in the Sistan-Baluchistan province, IranThe Journal of Infectious Diseases 07/2003; 187(11):1828-9. DOI:10.1086/375250 · 5.78 Impact Factor
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ABSTRACT: Acute haemolysis associated with clinical episodes of high-level Plasmodium falciparum parasitaemia was studied in 20 children from an holoendemic area (coastal Tanzania). The change in blood haemoglobin (Hb) concentration ranged from -46 to g/L during the 72-h observation period and was linearly related to maximum parasitaemia. Balance studies between loss of blood Hb, increase in plasma Hb and appearance of Hb in the urine indicated that extravascular clearance of red cells was the predominant mode of erythrocyte clearance. Most subjects, however, showed minor signs of intravascular haemolysis. The plasma Hb was < 1% of blood Hb and haemoglobinuria was detected in 14/20 children but the excretion of Hb in urine was < 0.5% of total Hb loss. Haemoglobinuria was, however, a marker of severe haemolysis, since the maximum blood Hb loss in children without haemoglobinuria was 10 g/L. Erythrocyte-bound opsonins known to induce erythrophagocytosis, i.e., complement C3c fragments and autologous IgG, were increased in all patients. In the patients with major haemolysis, the changes correlated to the haemolysis over time. Hence, a similar mechanism for predominantly extravascular erythrocyte clearance may be operative in acute malarial anaemia, normal erythrocyte senescence and other forms of acute haemolysis.Transactions of the Royal Society of Tropical Medicine and Hygiene 11/2001; 95(6):611-7. DOI:10.1016/S0035-9203(01)90095-1 · 1.93 Impact Factor
Article: Daily dynamics of Plasmodium falciparum subpopulations in asymptomatic children in a holoendemic area.[Show abstract] [Hide abstract]
ABSTRACT: Plasmodium falciparum is the major cause of malaria morbidity and mortality in the world. Biologic and antigenic diversity is a characteristic of this parasite and infections can consist of several genetically diverse parasites. The daily dynamics of these parasite subpopulations were investigated in asymptomatic children in rural Tanzania. Fingerprick blood samples were collected on 14 consecutive days from 20 children. Parasite densities were detected by light microscopy and genotyping of P. falciparum was done using a nested polymerase chain reaction (PCR) assay targeting polymorphic regions on the merozoite surface protein-1 (MSP-1), MSP-2, and glutamine-rich protein (GLURP) genes. In the eight children harboring P. falciparum throughout the study period, infections were found to be highly complex with daily changes in both parasite density and genotypic pattern. A nonrandom. 48-hr periodicity in these fluctuations suggests that P. falciparum infections consist of inherently synchronous subpopulations of parasites. These findings have important biologic and epidemiologic implications since one blood sample may only partly reflect the whole parasite population in an infected individual.The American journal of tropical medicine and hygiene 06/1997; 56(5):538-47. · 2.74 Impact Factor
Article: Efficacy of oral and intravenous artesunate in male Tanzanian adults with Plasmodium falciparum malaria and in vitro susceptibility to artemisinin, chloroquine, and mefloquine.[Show abstract] [Hide abstract]
ABSTRACT: The clinical efficacy of oral and intravenous (iv) artesunate was compared in an open randomized trial in 50 male adult patients with uncomplicated Plasmodium falciparum malaria in Kibaha, Tanzania. Oral artesunate treatment was started with 2 x 50 mg initially followed by 50 mg 12 hr later and then 50 mg twice a day for four days (total dose = 550 mg or 9.6 mg/kg). Intravenous artesunate administration began with 2 x 0.8 mg/kg initially followed by 0.8 mg/kg 12 hr later and then 0.8 mg/kg twice a day for four days (total dose = 8.8 mg/kg). The mean +/- SD parasite clearance times (PCTs) were nearly identical at 23.4 +/- 5.9 hr and 24.2 +/- 7.2 hr after oral and iv administration, respectively. Mean +/- SD fever subsidence times (FSTs) were also similar at 18.7 +/- 8.3 hr and 21.0 +/- 4.8 hr, respectively. All patients remained negative for P. falciparum for at least 14 days. Recrudescence/reinfection occurred between days 21 and 28 in five of 25 patients (20%) after oral treatment and in four of 25 patients (16%) after iv treatment. The mean erythrocyte count and hemoglobin concentration were slightly reduced after iv treatment but remained in the normal range. Otherwise, there was no change in blood biochemistry, hematology, and electrocardiograms monitored prior to and during the last dose. It is concluded that treatment with oral and iv artesunate was equally efficacious and well tolerated. A 24-hr in vitro susceptibility test of P. falciparum to artemisinin, chloroquine, and mefloquine was performed in samples from all patients. The three compounds exhibited 100% inhibition with the exception of three isolates, which showed chloroquine resistance. Parameter estimates of a sigmoid Emax model (drug concentration at which 50% of the growth inhibition occurs [EC50]), the sigmoidicity factor s and EC95 fitted to the growth inhibition data differed between compounds and isolates, indicating different sensitivity of P. falciparum isolates. There was no correlation between artemisinin and mefloquine EC50 values, while artemisinin and chloroquine EC50 values showed weak correlation (r2 = 0.223, P = 0.006). There was no correlation between parameters describing clinical outcome (the PCT, the time needed for reduction of the parasite density to 50% and 95% of the initial parasitemia, and the FST) and those describing in vitro susceptibility.The American journal of tropical medicine and hygiene 01/1996; 53(6):639-45. · 2.74 Impact Factor
Article: Concentration and time dependency of artemisinin efficacy against Plasmodium falciparum in vitro[Show abstract] [Hide abstract]
ABSTRACT: A chloroquine-sensitive strain of Plasmodium falciparum, F32, from Tanzania was exposed during continuous culture to concentrations of artemisinin, 10(-8)-10(-5) M, with exposure times ranging from 1 to 96 hr. After drug exposure, the cultures were washed and the incubation was continued for one or two parasite cycles to assess the remaining viability of the parasites. Artemisinin at a concentration of 10(-6) M inhibited parasite growth by 63% within 3 hr of drug exposure. The parasitemia then continued to decrease after removing the drug by washing the cultures. A 95% inhibition was thus observed 48 hr later. For 100% inhibition, at least 12 hr of exposure to 10(-6) M artemisinin was required. The compound at a concentration of 10(-7) M inhibited growth by 86% within 24 hr of drug exposure and by 98% 48 hours after removing the drug. A concentration of 3 x 10(-8) M exhibited 97-100% inhibition only after 72 or 96 hr of drug exposure, while 10(-8) M did not have any appreciable effect on the growth of the parasites even after 96 hr. It is concluded that artemisinin at high concentrations has a significant rapid in vitro effect that appears to be highly parasitocidal. The compound appears to have a broad spectrum of action, not only schizontocidal as reported earlier, but also against the asexual blood stages of P. falciparum.The American journal of tropical medicine and hygiene 07/1994; 50(6):771-6. · 2.74 Impact Factor
Top Journals
Karolinska University Hospital
Tukholma, Stockholm, Sweden
- Department of Infectious Diseases
Karolinska Institutet
Solna, Stockholm, Sweden
- Department of Infectious Diseases
Pasteur Institute of Iran (IPI)Teheran, Tehrān, Iran
Uppsala University
Uppsala, Uppsala, Sweden
- Department of Pharmacy


text:
An Unlikely Match
by Sarah M. Eden
Product Description
It isn't every day an impoverished young gentleman inherits a sizable fortune and an estate. Nickolas Pritchard, not only impoverished and young, but a gentleman as well, felt his luck acutely the day just such a remarkable inheritance fell upon him.
The future has never looked brighter for once penniless Nickolas Pritchard. Now in possession of an unforeseen legacy from a distant cousin, he can finally woo the exquisite Miss Castleton, belle of the London Season. What better setting for matchmaking than Ty Mynydd, his ancestral home nestled in the untamed hills of Wales? Ideal, indeed . . . except for the ghost.
For nearly four hundred years, Gwen has walked the halls of the home in which she lived — and died a mysterious death. But despite centuries as the reigning force within her ancient residence, nothing prepares her for the charm and unexpected appeal of Englishman Nickolas.
A deep and abiding affection grows between the two, tempered by the unbreakable barrier that separates them. They cannot possibly hope for a happily ever after. there can be no future between a man yet living and a woman long dead.
But how can Nickolas possibly give Gwen up? And how can Gwen face an eternity without Nickolas?
Product Details
By Gelise , Submitted on 2015-02-25
Sarah M Eden has created a story unlike any other she's ever written. It's magical and fantastic how she added the supernatual in the regency era. I love it. I love it.
By Tonya W., Submitted on 2015-02-25
This is a very interesting book. I thought it a little odd to begin with, but couldn't put it down and finished it breathless. I read it in one day! Don't miss this one!!
By Shauna, Submitted on 2015-02-25
WOW! This book is AMAZING!
Nickolas has gone from being impoverished to inheriting~ Y Castell.
A castle where 400 years ago a battle was waged between the Welsh and the English
Only there is a situation in the castle...it is haunted...
Haunted by Gwen, the girl who died during that battle.
As in ALL romance stories...Nickolas and Gwen fall in love...
Can a ghost and a human who is 400 years younger make it work?
Only Sarah Eden can pull a twist that is so tender and so suspenseful and so...
If you like Regency Romances you really need to read this one :)

subset: commoncrawl


text:
Wednesday, March 03 15 / htm
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Lovers whose relationship is doomed to fail are said to be "star-crossed" (frustrated by the stars), because those who believe in astrology claim that the stars control human destiny. William Shakespeare used the phrase to describe the lovers in Romeo and Juliet.
A phrase from the play Romeo and Juliet, by William Shakespeare; Romeo and Juliet are so described in the prologue to the play.
Note: "Star-crossed lovers" refers to any lovers whose affection for each other is doomed to end in tragedy.
Amid the chaos and carnage, star-crossed lovers Jon Snow (Kit Harington) and Ygritte (Rose Leslie) meet on the battlefield.
star-crossed lovers of Verona, young victims of an ancient family feud, doomed to die tragically—we all know how it goes.


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Who can do Gay Pride 2015 better than underwear models? We always catch them in little-to-no clothing, and always with a body that's made to be exposed.Read More
Who can do Gay Pride 2015 better than underwear models? We always catch them in little-to-no clothing, and always with a body that's made to be exposed.
Even men who prefer a classic look struggle to find the right pairs of white underwear. Most men opt out of white underwear because it doesn't stay white.
Walter Delmar took his body to the L.A. River for a photoshoot with Himsight Photography. It wasn't the brightest summer day, but moody skies suit his look.Read More
We'd probably all like to go on a date or two with an AC man, but for those of us lacking our own model boyfriend, there's the Andrew Christian Dating Game.Read More
The Blue Code attitude is all about masculinity and freedom. Chema Trezze is photographed by Sergi Jasanada in the current collection of Blue Code swimwear.Read More
Renowned photographer Pedro Virgil's Cocksox Editorial for S/S15 if finally here. You've already seen the bright summer colors and the CXSH Sheer Range.Read More
Alex is buff and ready for battle in his Xtremen boxers. The new photoshoot by Armando Adajar captures the athlete in six of the brand's boxer designs.Read More
The talented Adrian C. Martin photographed newcomer Gianni Reyes modeling Aware Soho briefs. Gianni Reyes also models running shorts and a sexy mesh trunk.Read More
The Underwear Expert is here to remind you – with our latest Jerrad Matthew exclusive photoshoot – that there's underwear designed for well-endowed men.
Model Andre Costa wears several pairs of Papi underwear for the brand's latest lifestyle shots. The photoshoot is part of the brand's current rebranding.Read More


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- Chicago Bulls introduce first round pick Bobby Portis Updated: Jun-29-15 5:48 pm
CHICAGO - Growing up, Bobby Portis got accustomed to being the last player picked. So he prided himself on being the one who out-worked everyone else.
- Chicago Bulls take Arkansas' Bobby Portis with 22nd pick Updated: Jun-26-15 12:39 am
CHICAGO - The Chicago Bulls figured Arkansas power forward Bobby Portis would be gone by the time they picked. Once their turn came, the decision was easy.


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Keeler in the Morning
A Utica area native who has worked in Albany, Syracuse, Providence and of course, Utica.
Thursday, April 2nd, 2015
Today we talk Education Reform with Assemblyman Anthony Brindisi and Senator Joe Griffo. Also, the Utica Comets are going to the playoffs and we'll drink some craft beer with John Naegele.
The Utica Comets (42-19-6-1) came one step closer to clinching a berth in the AHL playoffs on Wednesday night in front of a near capacity crowd at the Utica Memorial Auditorium. The Comets, first place in the Northern division of the Western Conference, skated past rival Rochester 5-1 to come ever so close to clinching a playoff spot
The New York Jets are playing it closer to home this summer.
There's certainly been a lot of talk in New York State about our failing schools; so, how bad is it really? The answer might just surprise you, especially after all of the rhetoric coming over the last several months from Governor Andrew Cuomo who is on a mission to fix New York's broken schools.
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Results from a flirting test on Queendom.com reveal that men and women not only enjoy flirting, but many do it in order to get what they want. Their data showed that while women did have a slightly higher tendency to flirt, it was men who fared slightly better in terms of flirting expertise and techniques.
"Men aren't as cavemen-ish when they flirt as some women may think," said Vrat Jerabek, president of the company. "For instance, 11 percent of men who took our test would easily and shamelessly flirt with a female officer to get out of a ticket, compared to 8 percent of women. Men also used their flirting skills to get a deal on a car (20 percent), and a surprising 6 percent of them would actually date her in order to get a deal later on."
"We are certainly hot-wired to flirt by our genetics, and the best flirts have had the best chances of propagating. The body language used in flirting in various cultures has the same basic components intense eye contact, smile, hair toss and coy glances for the ladies, chest puffing in men... So there is certainly a genetic component," Jerabek said in a release about the survey. "Flirting is more than genes dictating our movements. It's also a skill based on social learning and learning by observing adult subject matter experts."
The study also revealed that men's most popular flirting gestures when chatting with a woman are to smile and to lean in to show interest, while women smile and look deep into a man's eyes.
Other interesting tidbits:
45 percent of men would converse with someone they found hot at a funeral
36 percent would ask that person out, while still at the funeral (55 percent and 19 percent respectively for women).
Only 10 percent of women would flirt with a male car salesman in order to get a better deal.
Apparently, both men and women love to flirt. It's fun and relatively harmless. But, does flirting with an ulterior motive cross the line?


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|HF with office in FrankfurtHi guys and girls, which hedge funds/alternative investment managers do you know with an office in Frankfurt. Here is my list so far - Apollo - Fortress - LoneStar - Oaktree Would say, they are all first tier. Do you know any second tier? Thanks Anira
|2 years 4 months
|Hudson Advisors => Distressed HFHi, How good are your chances to move from Hudson Advisors (NPL underwriting) to a Distressed HF? Thanks Anira
|2 years 7 months
|Hudson AdvisorsHi together, first of all: I was not sure where to post this, so hope PE is right. Does anyone know anything about Hudson Advsiors regarding lifestyle and culture? Thanks! Anira
|2 years 7 months
|What strategies do (prop) traders useHi everyone, I know a little bit about trading strategies e.g. using Momentum. But what do the prop traders use? Ìs it basically the same just more sophisticated? And how do floor traders place their trades? do they use any strategy or do they just pass through the trades? Thanks Anira
|5 years 10 months
|Trading: Hot topics for my thesis?Hi together, First of all happy new year to all of you. I am currently looking for a subject for my thesis and I would love to do something trading related. It is not so much the research focus of my prof but he is fine with me suggesting him a topic for my "trading-thesis". So, now it is up to...
|6 years 6 months
|Trading simualtionHi together, does anyone of you know a trading game that simulates everyday´s traders work realistically, so you can try whether I am have the ability to trade or not and if it´s fun... Many thanks!
|8 years 1 week
|MBA or MSc Quant FinanceHello together, what would you recommend someone who wants the opportunity/possibility to work for a HF (and is currently working in consulting)? Many thanks, AniraX
|8 years 2 weeks
|next stupid question: does a CAIA help in S&T?Or do you know any other similar qualification that might help?
|8 years 1 month
|MBA for S&THello together, would a mba help to do a career change towards S&T or would a msc in finance better? have a nice day AniraX
|8 years 1 month
|CFA - usefull for structuring?Hello together, how much does a CFA exam helps you if you (want to) work in structuring derivatives? Have a nice day, AniraX
|8 years 1 month
|Hudson AdvisorsAsking as potential employee.
|2 years 4 months
|HF with office in FrankfurtThanks a lot, Kenny, for the confirmation. Any chance you know some more funds with office in Frankfurt?
|2 years 4 months
|Planning for Exit OppsPE: Best would be to work in the PE group doing a lot of DDs. However, you only see the commercial part. CFA is nice but not soo important if you have a decent financial knowledge anyway. HF: Here I am just guessing. If you build knowledge in an industry that might help, if a HF is looking for...
|2 years 4 months
|HF with office in FrankfurtThat's a good point. Based on their focus on distressed opportunities rather than classical LBO/buy-outs, I thougt they are more HF than PE (but I know that they also have PE teams).
|2 years 4 months
|Hudson Advisors => Distressed HFThat's true. My research so far shows that these moves happen from time to time... Thanks for your answer!
|2 years 6 months
|What's worse for Consulting: Audit or...From a European perspective I would go for JPM as internship to have the brand on your CV
|2 years 7 months
|Best Major(s) for MBB Consulting?Engineering or science like maths, physics,... are sought after due to their analytical skills, but in general, it doesn't really matter.
|2 years 7 months
|Watches for the ladies?I am a girl and into watches :-) Don't know if it helps as I asume they are not that popular in the US, but for me, the best value for money you get at Sinn: http://www.sinnwatch.com/
|4 years 9 months
|What strategies do (prop) traders use[quote=artmonkey]Do you really think anyone divulge this information so easily?[/quote] Thanks for your answers and the link. Of corse I am not hoping for someone explaining ther strategy in detail. I know some books wirtten for private day traders like e.g. "High Probability Trading...
|5 years 10 months
|Trading: Hot topics for my thesis?The topic should be for my master thesis. Ideally it could also be used for a PHD, which I hope to do directly after the master/after an internship in S...
|6 years 6 months


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http://www.adventuresofgeorgiapotter.com Georgia's adventures in Lightning Ridge. The adventures of a real girl in Outback Australia. Produced by http://www.authenticholidayfilms.com


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1965 Chevrolet Corvair Monza Sport Sedan 4dr. hardtop. Corvair made no cars with center B pillar door posts from 1965-1969 and this is one... More
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1972 Chevrolet Camaro Z-28, original unrestored example, original paint & interior. 21,000 actual miles, 350 LT-1, #'s match, TH400 Auto, 3:73 Posi, original build... More
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Women's bantamweight fighter Roxanne Modafferi recently attended the 2013 World MMA Awards in Las Vegas, and put together a vlog that includes a good-natured send up of Wanderlei Silva, set to the tune of What Does the Fox Say.
Related MMA gear from the UG Store
Recent Comments »
2/10/14 6:39 PM by tecknowledge
2/10/14 3:24 PM by deadlysyn
2/10/14 3:08 PM by get ya tits out
dana white won best mma fighter
2/10/14 3:00 PM by House Boru
Roxy was having a great time and i had a great time watching her have it
2/10/14 2:32 PM by Kirik
Try again. The embed was switched.
2/10/14 1:29 PM by Krypstonite
You are right. Sir.
2/10/14 1:24 PM by austinjames427
Wouldn't it?
2/10/14 1:21 PM by I0thCatchJitsu
Would be nice if link worked...


text:
Originally written on WhoDeyFans | Last updated 4/1/13
I'm happy to report that I've finally emerged from a bout of seclusion that would have made a hermit cringe. For the past year, I've been busy writing a book about the NFL Draft that should be published later this month. And because I bleed orange and black, it will feature a healthy amount of Bengals content. Now I'm finally free to write about the upcoming draft and share some of my thoughts on the best moves for the Bengals this year. But I'll also be sharing some of the information from the book that I found interesting. And I'llbe doing it for the next 25 days to get Bengal Nation ready for the draft on Thursday, April 25th. Did you know? The first draft pick ever, Jay Berwanger, a halfback from the University of Chicago, never played pro football. Bengals Thought: I'd like to see Cincinnati go after another halfback this year, Tavon Austin, but early estimations have him getting selected before the Bengals draft pick at No. 21. Thus, I'll explore some contigency plans in future posts.
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Alzada M. Hagins
North Carolina's long-running academic fraud scandal now includes five NCAA charges, including a lack of institutional control for poor oversight of an academic department popular with athletes and the counselors who advised them.
WASHINGTON - A majority of Americans support allowing immigrants living in the country illegally to stay and be granted legal status, according to a new poll released Thursday.
GREENVILLE, Ga. - Ghost hunters tell stories of gruesome crimes. Former guards remember an underground dungeon. A crowd is said to have gathered to witness the hanging of a prisoner. So is the lore of the old Meriwether County jail, a 119-year-old relic that is being renovated into a home and museum.
DUBLIN, Ohio - Hideki Matsuyama was bracing for a rough day at the Memorial and wound up with a share of the lead Thursday.
NEW YORK (AP) - How much scandal is too much scandal?
Mr. Jason Grant Meeks
As former WNBA player Coretta Brown walked through the halls of Southeast Bulloch High School, she noticed a few changes.
PHOENIX - A.J. Pollock homered for the second consecutive game, and the Arizona Diamondbacks rallied for a wild 9-8 win over the Atlanta Braves on Wednesday.
Charles Winfield Morel Jr.
MACON, - Georgia coach Mark Richt hopes there is room for "discretion" in the SEC's new rule which blocks schools from accepting transfers who have had "serious misconduct" problems.
Benita Palmer officially achieved her lifelong dream of home ownership with a simple signature.
According to Bulloch County Chief Deputy Jared Akins, runaway juvenile Lauryn Carswell, 15, has been located and is in custody and safe.
A train struck a truck Friday afternoon on Old River Road at Maria Sorrell Road, and the driver had to be cut from the wreckage.
Diane Green Allmond
WASHINGTON - Doug Fister said he really hadn't heard about the scoreless innings streak being crafted by his fellow Washington Nationals starters.
OTTAWA, Ontario - The last time the United States played China in the Women's World Cup was in the 1999 final at the Rose Bowl, when the Americans won on penalty kicks for their second title and Brandi Chastain famously ripped off her jersey.
NEW YORK - The Minnesota Timberwolves got their man in the middle. The Lakers got a playmaking partner for Kobe Bryant.
OMAHA, Neb. - Winning, and winning big, has been the standard for theVirginia baseball program since coach Brian O'Connor took over in 2004, and no excuses were allowed when the most trying circumstances cropped up.
More than 35,000 college athletes and cadets at U.S. service academies are helping researchers write a new, extensive and groundbreaking chapter in the study and tracking ofconcussions.
Note: All information included in this report is taken from law enforcement incident reports and arrest records, which are public records and available for review at any and all local law enforcement agencies. Not every arrest leads to a conviction. Guilt or innocence is determined by the court system.
WASHINGTON - Alexander H. Stephens, onetime vice president of the Confederacy, sits memorialized in stone, right leg crossed over left, staring sternly into the distance as summer-clad tourists mill about him in the U.S. Capitol's Statuary Hall. Solemn and cold, he looks like he could sit there for eternity.
ATLANTA - More than 412,000 Georgians can receive tax subsidies designed to make health insurance affordable after the U.S. Supreme Court upheld the nationwide assistance in a ruling Thursday.
WASHINGTON - The Supreme Court sent a clear message Thursday that President Barack Obama's health care overhaul is here to stay, rejecting a major challenge that would have imperiled the landmark law and health insurance for millions of Americans.
Mr. Harold "Round Man" Lowery
WASHINGTON - Ian Desmond hit a sacrifice fly with the bases loaded in the bottom of the 11th inning to lift Washington to a 2-1 victory over the Atlanta Braves on Wednesday night for the Nationals' fifth straight victory.
In just five short years, the South Georgia Fury softball organization grew from humble beginnings to a powerhouse travel team organization on the rise.
They poach officers from nearby police departments. They entice recruits by playing up the drama and heroism of policing through video close-ups of flashing lights and holstered guns. They wrestle with how to offer better pay.
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Simon Ramsden signs two-year Motherwell deal
Simon Ramsden has signed a new two-year deal with Scottish Premier League runners-up Motherwell.
The defender joined the Steelmen from Bradford last summer and has made 30 league and European appearances.
The 31-year-old Englishman said: "I'm very happy here. We've settled here nicely. It's just a pleasure to be involved with this team."
Ramsden's new deal will be welcome news for Motherwell fans who fear an exodus of key players from Fir Park.
Motherwell's performances this season have attracted suitors, with manager Stuart McCall being linked with Sheffield United , midfielder Nicky Law a target for Rangers, among others, and players' player of the year Michael Higdon very likely to be the subject of offers.
Simon Ramsden
"Some of the lads have had incredible seasons and there is going to be interest in them"
Goalkeeper Darren Randolph will join Birmingham on 1 July , and Well could also lose forward James McFadden and defender Tom Hateley.
As McCall's men prepare for the trip to Europa League-chasing St Johnstone, Ramsden says he is determined that the team should end the season, and possibly an era, on a high.
But he is not too despondent at the thought of the team being broken up, as long as McCall is there for the rebuild.
"Some of the lads have had incredible seasons and there is going to be interest in them," he said.
"From the club's point of view, it is a shame that we can't hang on to two or three more of them and build again for next season.
"But, as the manager has proven over the last couple of years, if a few go he will bring in a few more and we'll try and do well again next season."
Ramsden's first match in claret and amber last summer was against Panathinaikos and he can look forward to a further taste of European football, when Motherwell play in next season's Europa League qualifiers.
"To be able to make my debut in the Champions League was absolutely brilliant," he said.
"To finish second this season and be a major part of that - I've been very happy."
The versatile defender, who can also play in midfield, does not accept that the talk of players leaving the club has had a negative effect on performances.
He said: "I don't think it has distracted us. When there is interest in lads, they know they have to be at their best so it might have benefited us slightly. It's not something we talk about in the changing room.
"We'll get the game over on Sunday and see what happens with the squad."
Describing Higdon as "a handful" when the pair play against one another in training every day, Ramsden says he hopes that McCall is not poached from Fir Park.
He continued: "Personally it would be a huge loss [if he left] because this is the second time I have played under the manager.
"He signed me for Bradford and brought me up here.
"From the club's and the fans' point of view it would be a loss after what he has done over the last few seasons.
"But on the other hand the manager has just been given manager of the year in the SPL and clubs will be noticing how well he has done with such a small squad, so there is bound to be interest.
"We will all be hoping that he stays."
Comment number 14. Posted by NHSnurseon 18 May 2013 09:06
You have to love some or the more challenged posters on here. "What a waste of time and SPACE opening up this pos"t. So I will take up my time and use the SPACE to rant about it, talk about irony. As for somewhere on earth I find it sad that all you do is troll posts all day but hey if that's all you have to do in life batter in.
Comment number 13. Posted by The Acute Angleron 17 May 2013 23:42
So the re-signing of a potentially key defender by one of the very few Scottish clubs who will be playing in Europe is a "nothing" story? If that's true then the possible relegation of Hearts (because they're "only" bottom 6) or absolutely anything to do with Rangers (because they're lower league) has no place in any Scottish sports news coverage. Talk sense people. @7 you're a shocker.
Comment number 12. Posted by The BBC is Anti Scotlandon 17 May 2013 23:36
@7 your mum is the worst league in europe
Comment number 11. Posted by APon 17 May 2013 20:50
Certainly improved over the course of the season and worthy of a new deal. A few months into the season I would have been happy to let Cummins get the experience but Ramsden developed a good understanding with Hutchinson in the second half of the campaign.
Comment number 10. Posted by The Cloaking Device Has Malfunctionedon 17 May 2013 19:37
Fish supper blah blah blah.. I'm really funny...
Comment number 9. Posted by d23on 17 May 2013 19:20
so my initial comment seems to be valid - 8/9 comments on here so far have been derogatory towards the story.
Please think more about which threads you open up - use some common sense!
Comment number 8. Posted by djh222on 17 May 2013 19:02
@7 you're a disgraceful waste of space
@6 Simon Ramsden
Comment number 7. Posted by U15702244on 17 May 2013 18:35
All this user's posts have been removed. Why?
Comment number 6. Posted by _mitch_on 17 May 2013 18:33
Comment number 5. Posted by G_K___on 17 May 2013 17:49
Is he any relation of Harry?
I like a good fish supper, me.
Comment number 4. Posted by chin furyon 17 May 2013 17:09
I wasn't convinced by Ramsden at first but he has improved as the year has gone on. Getting regular games playing in a stable defence instead of being dropped for Cummins from time to time has really helped him.
It might not be a big name signing but considering before this our team for next year was Lasley and Hammell standing in a field, I'll take it.
Comment number 3. Posted by The BBC is Anti Scotlandon 17 May 2013 16:34
@2 totally agree. Nothing story let them comment. How long before it becomes a free for all on how rubbish scottish football is?
Why didn't they open comments on lomas statement that its ok to elbow an opponent in jaw once you looked at him to see where he is and make sure you get it right? Will be interesting to see if he wants cameras used when something goes against his side
Comment number 2. Posted by d23on 17 May 2013 16:18
BBC - why have you opened up a comment on this story, It is hardly a major story (no offence to Motherwell fans)?
There seem to have been many football related threads opened up today, with most other sports having no articles open to comment on (rugby hasn't had a thread open for a couple of days).
Regarding the story, good luck to the lad, and Motherwell next season.
Comment number 1. Posted by The BBC is Anti Scotlandon 17 May 2013 14:48
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Fantastic perspective on the tower, wonderful composition. All Best Wishes, from Rome and Merry Christmas, Luka
Thank you very much for your nice comments Luka!
Beautiful shot Tomas: fantastic sharp image. Excellent...
Best Regards,
Thanks for your visit Séan!
In this case I have to admit that I used the smart sharpen filter in Photoshop to boost the sharpness a bit... I'm glad that you like the result though.
Cheers, Tomas
No issues there Tomas: that's digital photography.
Keep up the good work.
Very good the perspective chosen for this tower, Tomas. It highlights the beauty of the top part that is the most beautiful. Congratulation.
Regards, Arturo.
Thanks for your nice words Arturo!
Cheers, Tomas
Photo taken in 53100 Siena, Province of Siena, Italy


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2004 Ford Explorer Q&A
2004 Ford Explorer Question: car vibrates
everytime i make a turn when going slow me car vibrates - j1828
Answer 1
Is your Ford Explorer 4wd or all wheel drive? Making sharp turns on dry pavement with the 4 wheel drive engaged will cause the drive line to bind up which could be described as a vibration. 4 wheel drive systems are not designed to operate in 4 wheel drive mode on dry pavement. They do not have a center differential which will allow for the different wheel speeds between the front and rear wheels. All wheel drive systems are designed with a center differential which will compensate for the different wheel speeds. If your Explorer is 2 wheel drive this should not be a problem. IF your Explorer is 4 wheel drive your transfer case may be in the 4 wheel drive mode. If your Explorer is All wheel drive you may have in internal problem with your transfer case. - Russ
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I was so excited to receive this wonderful account of Adelie Filippi's visit to Aztecs: Conquest and glory. In the following Adelie shares her thoughts on her visit and best of all gives Te Papa the big thumbs up. Thanks Adelie! Recently I went to Te Papa with my aunt and uncle, they were taking… Read more »
Posts categorized as Exhibitions
Wearable of the Week # 7
As October is Breast Cancer Month this week's fabulous wearable takes the form a bizarre but very thoughtful bra – its Lynn Christiansen's The Abbey of St Brassiere. The witty and outrageous Bizarre Bra™ section has been a firm favourite with WOW® entrants and audiences since it was established in 1995. Since then, more than 400… Read more »
Wearable of the Week # 6
Over 100 WOW® fans crammed into Te Papa's Eyelight's Gallery last Saturday to hear the maker of this week's wearable speak. Its Bells for Her by Sean Purucker. Sean Purucker lives in LA where he works as a costume fabricator. He grew up, however in Alaska. Bells For Her harks back to his Alaskan childhood – to… Read more »
Bridging the gap: Monet and American artists at Giverny
In 1883, Monet moved to the village of Giverny, downstream along the Seine from Vétheuil, retreating further from the hustle and bustle of modern life in Paris. In the late 1880s increased sales of his work through the dealer Paul Durand-Ruel's gallery enabled him to purchase a house and modest estate. There, in a plot… Read more »
Colour my World!
Over the past six weeks we have been having some serious problems with StoryPlace…. Before every session, it would miraculously lose all its colour!! Luckily, our young visitors and their caregivers were kind enough to help to collect enough red, blue and yellow to remedy the situation. Did you know that red and blue can… Read more »
Wearable of the Week # 5
Wellington has moved into full WOW® mode this week, and Te Papa is in the midst of the whirlwind. Yesterday morning we welcomed 50 international WOW® designers onto Te Papa's marae, and hosted 250 designers, would-be entrants, fans and creatives at a Design Forum in the afternoon. Lynn Christiansen, the creator of this week's spikey 'wearable', was the afternoon's… Read more »
WearableArt™ Windows: Hannah – Wellington High School
For the final of our WearableArt™ themed windows we take a look at Wellington High School's Hannah who was inspired by a close up photo of seaweed. My name is Hannah van Seventer, I am currently taking Fashion Technology at Wellington High School. I am excited to have been given the opportunity to be a… Read more »
WearableArt™ Windows: Lia – Queen Margaret College
Our second to last of the WearableArt™ themed windows series features Lia of Queen Margaret College and her take on the Kowhai flower. My name is Lia Penny and I am currently in Year 13 studying Materials Technology at Queen Margaret College. I am thrilled to have been given the opportunity to make a wearable… Read more »
WearableArt™ Windows: Maia – Wellington High School
Our WearableArt™ themed windows series continues with Maia from Wellington High School and another take on the Longhorn Beetle image from yesterday. My name is Maia Holder-Monk and I am in Year 13 student studying Fashion Technology at Wellington High School. The photo of the Longhorn Beetle jumped out at me with its vivid colours… Read more »
WearableArt™ Windows: Rosie – Queen Margaret College
Our WearableArt™ themed windows series continues today with Rosie from Queen Margaret College and her take on a black bumblebee. My name is Rosie Reid and I am a year 13 student, studying materials technology at Queen Margret College. I enjoy the innovation and creativity associated with this subject, so being given the opportunity to… Read more »


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Huntsville and Green Bay airports and terminals
Airports in Huntsville AL, US
Huntsville Int'l (HSV)
Distance from City Center: 12.2 miles
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Austin-Straubel Field (GRB)
Distance from City Center: 7.8 miles
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The Huntsville International Airport services Huntsville, Alabama. The airport offers flights from Huntsville aboard multiple airlines, both domestically and internationally. Reservations can be made using Orbitz.com on airlines including American, AirTran, Delta, and United, among others. The airport, which served over 1.2 million passengers in 2011, is located at 1000 Glenn Hearn Blvd., about nine miles from the city's central business district.
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Visitors to Green Bay will find a wide variety of interesting things to do. Lambeau Field is home to the Green Bay Packers football team. It also houses a pro shop, The Packers Hall of Fame, Curly's Pub and Atrium dining. Events are held at the stadium year round. Green Bay Botanical Gardens are open all year, and it features flowers and plants from around the region. Orbitz.com can help you locate cheap flights to Green Bay.
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Tabletop & Bar
- Milady 5-Piece Flatware Place Setting $69.95 – $279.80
- Milady 4-Piece Hostess Set $179.95
Ordered these wine glasses, and then saw some at a competitor substantially less in cost, which made me consider my email purchase. However, when they arrived, I was highly impressed with the quality for the price. These are outstanding, ...
I have been shopping WS flatware for years, and this is the one I wanted, not made in China. FYI any rust spots are from neighboring steel in the dishwasher. Rinse agents will help. Stainless actually doesn't produce rust, ...
We used these to toast for our wedding pictures. They are great! Modern but traditional. They looked great in pictures too!


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Secondary menu
Everything you need to know about France's coolest treehouse/church.... READ ON
"It never dawned on me that I had any shot at being an artist."... READ ON
Laughter may be a universal language, but not every country chuckles at the same jokes. Here are a few international knee-slappers to bring down the house the next time you address the United Nations.... READ ON
Your next birthday might have you feeling old, but it's nothing compared compared to these senior citizens.... READ ON
Want to make a worker astonishingly more efficient? Give him the right tool? ... READ ON
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Use these tips to say hello like a local.... READ ON
Most plants are sweet, sunlight-chugging citizens. These carnivorous kingpins are not. ... READ ON
Once upon a time, fairy tales were dark fables designed to scare children into good behavior. This author thought kids deserved better.... READ ON
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- Hotel Management & Chef Traineeships at Vineyard Hotel & SpaPosted July 18, 2013
- Standard Bank Group Shared Services Learnership ProgrammePosted August 22, 2013
- John Thompson Apprenticeships (Boilermaking & Welding)Posted September 25, 2013
- Trainee Accountant Opportunities at eThekwini MunicipalityPosted July 15, 2014
- Conservation Worker Opportunities at SANBIPosted August 28, 2014
- Iemas Learnership Programme: Short Term InsurancePosted October 7, 2014
- Sales Learnership Opportunity at Auto & GeneralPosted November 6, 2014
- Basic Police Development Learning Programme (Gauteng) 2015Posted December 8, 2014
- Financial Services Learnership Programme at Sanlam 2015Posted January 13, 2015
- Nampak Apprenticeship ProgrammePosted March 6, 2015
Learnerships and Internships
Creative Learnership Programme at Umuzi Academy
DO YOU WANT TO BE PART OF THE CREATIVE ECONOMY? Umuzi Academy, an initiative by Umuzi, in partnership with Investec Bank, the Da Vinci Institute and The Creative Circle, are offering a one-year, paid learnership programme to...
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Sales Learnership Opportunity at SA Breweries (SAB)
South African Breweries is offering Sales Learmerships in Wadeville, Isando, Thohoyando, Polokwane, Tzaneen & Garankuwa. The key purpose is to provide people with an opportunity to enrol for a Further Education and Training Certificate (NQF 4) with...
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Internal Audit Learnership Programme at Iemas
Iemas, an authorized financial services provider, invites unemployed candidates from designated groups to participate in Internal Audit learnership at the head office in Centurion. The Learnership offers: An 18 month employment contract, with a monthly allowance of...
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Fashion Studio Internship at Zando
Online fashion retailer Zando, is looking for a Studio Intern in Cape Town, Western Cape. This opportunity is for an individual with a love for fashion that wants to do a paid internship to get great exposure...
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Sand Laboratory Technician Internship at Chem Systems
ChemSystems is looking to recruit a Sand Laboratory Technician Intern to work in Chloorkop. ChemSystems provides a diverse range of chemical products, chemical services and chemical solutions to a wide customer base in several industries. Requirements Matric/Grade...
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Welding Apprenticeship Programme at Stefanutti Stocks
The Oil and Gas Division at Stefanutti Stocks is currently recruiting five candidates to be selected for an Welding Apprenticeship in Secunda/ Sasolburg. The successful candidates will be placed on a full-time apprenticeship program and will be...
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Business Intelligence Learnership at AfriGIS
AfriGIS is looking for eager young individuals with a passion for technology to take part in our Business Intelligence Learnership Programme. The Learnership is based in Pretoria and offers an Advanced Certificate in IT Database Development (SAQA...
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Phlebotomy Technician Learnership Programme at Ampath
Excellent Learnership opportunity exists within Ampath to become a Phlebotomy Technician. Ampath has vacancies for a Phlebotomy Technician Learnership Programme in these areas: Gauteng/KZN/CAPE. Purpose of Position: To collect blood and non-blood specimens within a learning environment...
- Posted 10 days ago
Packaging Learnerships at SA Breweries (10 Positions)
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- Posted 11 days ago
Plant Operator Learnership ar Eskom (15 Posts)
Eskom has 15 Plant Operator Learnership opportunities at Kusile Power Station in Witbank, Mpumalanga. Requirements Grade 12/N3 with Physical Science and Mathematics Language include English as second language (50%) No experience required Skills and Competencies Computer literacy...
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Learnership Programme at FNB 2015
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- Posted 13 days ago
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Construction Operator/Driver Learnership at Raubex
Raubex, a well established construction company is providing leaners the opportunity to be part of a 12 month Construction Operator/Driver NQF2 learnership presented at their training centre in Bloemfontein. If you are serious about education and your...
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Surveying Learnership Opportuinty at Raubex
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- Posted 14 days ago
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- Posted 17 days ago


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The first issue of The Invisibles introduces us to Dane McGowan and his isolated rebellion. Dane's background as a teenager from a British industrial town, raised in a single parent household sets him up to be a young nihilist, our favorite kind. Fittingly, by the end of this issue, he has stolen a car, burned a library and a school, and seen the ghosts of two of the Beatles and a demon. The above panel takes its sequential place after Dane has assaulted his teacher, who is trying to stop him from burning the school. Earlier that day, the teacher had asked the class, "Can anyone tell me the name of the anarchist writer of 'Mutual Aid' who denounced the Bolshevik Revolution?'
It is appropriate that artist Steve Yeowell captures enraged Dane looking down on us from a skewed angle while yelling about Kropotkin, not only because it ties into that earlier question, but also because of the foundational Russian Anarchists' popularization of 'propaganda by the deed.' Often misunderstood as a political strategy of using property destruction and violence as a scare tactic, more recent works like Benedict Anderson's Under Three Flags: Anarchism and the Anti-colonial Imagination have argued that these acts were used to create media around anarchist ideas. The anarchists on trial would use their court time and final statements before execution to give speeches about their beliefs that were carried around the world by the increasingly global, news media.
Though Dane is being built up as a smart kid who is lashing out, this moment feeds well into the relations of the sign system Morrison built with the series. The Invisibles is well-known for its abundance of cultural references that resonate into the strange meta-physics he was proposing. And though I read this work as metaphor, giving it less power than the realism Morrison has attributed to it in his interviews, one would be hard to argue that the series did not gain a significant depth from its use of affective cultural undercurrents.
Colette Carr "Static" (video) (Premiere) // Music
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