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Publications (34)90.32 Total impact
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ABSTRACT: Resistance analysis from viral RNA is restricted to detectable viral load. Therefore, analysis from proviral DNA could help in cases with low-level or suppressed viremia. Viral plasma RNA and the corresponding cellular proviral DNA of 78 EDTA samples from 48 therapy-naïve (TN) and 30 therapy-experienced (TE) HIV-1-infected patients were isolated and analyzed for their resistance profiles in the protease and reverse transcriptase genes. Overall, 175 drug-resistance mutations (DRMs) were detected in 25/30 TE (83.3%) and 5/48 TN (10.4%) samples. The TE patients displayed a mean number of 6.68 DRMs in RNA and 5.20 in DNA. In the TN patients, a mean of 0.8 DRMs was found in RNA and 1.0 in DNA; 75% of the DRMs were detected in RNA and DNA simultaneously. In the TE samples, 76% of the DRMs were detected simultaneously in RNA and DNA, 23% exclusively in RNA and 1% in DNA only. The TN samples revealed a significantly higher frequency of DRMs in DNA than in RNA. Proviral DNA resistance testing provides additional resistance information for TN patients. It is also a reliable alternative for TE patients with unsuccessful RNA testing and can provide valuable information when no records are available. © 2015 S. Karger AG, Basel.Intervirology 06/2015; 58(3):184-189. DOI:10.1159/000431093 · 1.68 Impact Factor
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ABSTRACT: Introduction The health condition of HIV-1 infected patients has improved during the last years, but lifelong antiretroviral treatment is still needed. However resistance, multiple side effects and drug to drug interactions of antiretrovirals challenge the establishment of a long lasting regimen. The average running time of each antiretroviral drug composing the therapy episodes combination antiretroviral therapy (cART) may be seen as an indicator of effectiveness and tolerability. Materials and Methods To evaluate the running time of each drug used in HIV-1 treatment, we extracted therapy episodes from the latest release of the EuResist database (www.euresist.org). The evaluation period was from Oct 2006 to Oct 2012. Inclusion criteria for this analysis were continuous patient monitoring for at least two years (i.e. latest therapy start in Oct 2010), and the extraction of at least 100 cases per drug analyzed. Drug intake interruptions of less than a month were ignored. Results At the time of data extraction (Feb 2013), the EuResist database contained data from 61,953 patients of which 11,499 fulfilled the inclusion criteria. We obtained 37,035 drug treatment lines from 38,153 cARTs and the overall average length of drug intake was 18.7 months. For each single drug these average durations measured in months were: 18.3 (3TC); 20.8 (ABC); 12.3 (d4T); 14.3 (ddI); 23.2 (FTC); 23.0 (TDF); 13.4 (ZDV); 19.8 (EFV); 21.9 (ETR); 17.7 (NVP); 19.2 (ATV); 22.7 (DRV); 18.7 (FPV); 17.9 (LPV); 15.2 (SQV); 14.6 (TPV); 22.6 (RAL); 21.9 (MVC) and 8.9 (T20). Overall drug discontinuation rates at one, two and three years were 35.0, 48.8 and 95.8%, respectively. Average discontinuation rates for the different drug classes at two years these were: 46.2% for NRTIs; 49.7% for NNRTIs; 55.4% for PIs and 37.6% for Raltegravir/Maraviroc. Conclusions In this cohort the overall frequency of therapy changes is high. After two years of treatment, on average 49% of the patients change at least one drug in their cART. Thus, we have to expect numerous changes in the long term perspective of treatments. The observed differences in durations suggest that newer drugs might have advantages over older ones. However possible reasons and confounding factors (such as number of past treatment lines, co-medication, risk group, etc.) were not addressed at this time of the analysis.Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19790. DOI:10.7448/IAS.17.4.19790 · 5.09 Impact Factor
Article: Estimating Trends in the Proportion of Transmitted and Acquired HIV Drug Resistance in a Long Term Observational Cohort in Germany[Show abstract] [Hide abstract]
ABSTRACT: Objective We assessed trends in the proportion of transmitted (TDR) and acquired (ADR) HIV drug resistance and associated mutations between 2001 and 2011 in the German ClinSurv-HIV Drug Resistance Study. Method The German ClinSurv-HIV Drug Resistance Study is a subset of the German ClinSurv-HIV Cohort. For the ClinSurv-HIV Drug Resistance Study all available sequences isolated from patients in five study centres of the long term observational ClinSurv-HIV Cohort were included. TDR was estimated using the first viral sequence of antiretroviral treatment (ART) naïve patients. One HIV sequence/patient/year of ART experienced patients was considered to estimate the proportion of ADR. Trends in the proportion of HIV drug resistance were calculated by logistic regression. Results 9,528 patients were included into the analysis. HIV-sequences of antiretroviral naïve and treatment experienced patients were available from 34% (3,267/9,528) of patients. The proportion of TDR over time was stable at 10.4% (95% CI 9.1–11.8; p for trend = 0.6; 2001–2011). The proportion of ADR among all treated patients was 16%, whereas it was high among those with available HIV genotypic resistance test (64%; 1,310/2,049 sequences; 95% CI 62–66) but declined significantly over time (OR 0.8; 95% CI 0.77–0.83; p for trend<0.001; 2001–2011). Viral load monitoring subsequent to resistance testing was performed in the majority of treated patients (96%) and most of them (67%) were treated successfully. Conclusions The proportion of TDR was stable in this study population. ADR declined significantly over time. This decline might have been influenced by broader resistance testing, resistance test guided therapy and the availability of more therapeutic options and not by a decline in the proportion of TDR within the study population.PLoS ONE 08/2014; 9(8):e104474. DOI:10.1371/journal.pone.0104474 · 3.23 Impact Factor
Article: Novel tetra-peptide insertion in Gag-p6 ALIX-binding motif in HIV-1 subtype C associated with protease inhibitor failure in Indian patients[Show abstract] [Hide abstract]
ABSTRACT: A novel tetra-peptide insertion was identified in Gag-p6 ALIX-binding region, which appeared in protease inhibitor failure Indian HIV-1C sequences (odds ratio 17.1, P < 0.001) but was naturally present in half of untreated Ethiopian HIV-1C sequences. The insertion is predicted to restore ALIX-mediated virus release pathway, which is lacking in HIV-1C. The clinical importance of the insertion needs to be evaluated in HIV-1C dominating regions wherein the use of protease inhibitor drugs are being scaled up.AIDS (London, England) 08/2014; 28(15). DOI:10.1097/QAD.0000000000000419 · 5.55 Impact Factor
Conference Paper: Novel roles for Gag mutations in HIV-1 PI resistanceThe 20th International AIDS Conference (AIDS 2014), Melbourne, Australia; 07/2014
Article: Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort[Show abstract] [Hide abstract]
ABSTRACT: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients. We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples. 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching. Drug resistance increased in this single patient. Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation. Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route. We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment.BMC Infectious Diseases 11/2013; 13(1):537. DOI:10.1186/1471-2334-13-537 · 2.61 Impact Factor
Article: HIV-1 subtype is an independent predictor of reverse transcriptase mutation K65R in HIV-1 patients treated with combination antiretroviral therapy including tenofovir[Show abstract] [Hide abstract]
ABSTRACT: Subtype-dependent selection of HIV-1 reverse transcriptase resistance mutation K65R was previously observed in cell culture and small clinical investigations. We compared K65R prevalence across subtypes A, B, C, F, G and CRF02_AG separately in a cohort of 3076 patients on combination therapy including tenofovir. K65R selection was significantly higher in HIV-1 subtype C. This could not be explained by clinical and demographic factors in multivariate analysis suggesting subtype sequence-specific K65R pathways.Antimicrobial Agents and Chemotherapy 11/2012; 57(2). DOI:10.1128/AAC.01668-12 · 4.48 Impact Factor
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ABSTRACT: Etravirine (ETR) is a next generation non-nucleoside reverse transcriptase inhibitor (NNRTI). The studies for ETR EMA approval were almost exclusively performed together with the protease inhibitor (PI) darunavir. However the fact that ETR can be active against NNRTI-pretreated HIV variants and that it is well tolerated suggests its application in PI-free antiretroviral combination therapies. Although approved only for PI-containing therapies, a number of ETR treatments without PIs are performed currently. To evaluate the performance of ETR in PI-free regimens, we analyzed the EURESIST database. We observed a total of 70 therapy switches to a PI-free, ETR containing antiretroviral combination with detectable baseline viral load. 50/70 switches were in male patients and 20/70 in females. The median of previous treatments was 10. The following combinations were detected in the EURESIST database: ETR+MVC+RAL (20.0%); ETR+FTC+TDF (18.6%); 3TC+ETR+RAL (7.1%); 3TC+ABC+ETR (5.7%); other combinations (31.4%). A switch was defined as successful when either ≤50 copies/mL or a decline of the viral load of 2 log10, both at week 24 (range 18-30) were achieved. The overall success rate (SR) was 77% (54/70), and for the different combinations: ETR+MVC+RAL=78.6% (11/14); ETR+FTC+TDF=92.3% (12/13); 3TC+ETR+RAL =80.0% (4/5), 3TC+ABC+ETR=100% (SR 4/4); and for other combinations=67.6% (23/34). These SR values are comparable to those for other therapy combinations in such pretreated patients.Journal of the International AIDS Society 11/2012; 15(6):18260. DOI:10.7448/IAS.15.6.18260 · 5.09 Impact Factor
Article: Endogenous or exogenous spreading of HIV-1 in Nordrhein-Westfalen, Germany, investigated by phylodynamic analysis of the RESINA Study cohort[Show abstract] [Hide abstract]
ABSTRACT: HIV's genetic instability means that sequence similarity can illuminate the underlying transmission network. Previous application of such methods to samples from the United Kingdom has suggested that as many as 86% of UK infections arose outside of the country, a conclusion contrary to usual patterns of disease spread. We investigated transmission networks in the Resina cohort, a 2,747 member sample from Nordrhein-Westfalen, Germany, sequenced at therapy start. Transmission networks were determined by thresholding the pairwise genetic distance in the pol gene at 96.8% identity. At first blush the results concurred with the UK studies. Closer examination revealed four large and growing transmission networks that encompassed all major transmission groups. One of these formed a supercluster containing 71% of the sex with men (MSM) subjects when the network was thresholded at levels roughly equivalent to those used in the UK studies, though methodological differences suggest that this threshold may be too generous in the current data. Examination of the endo- versus exogenesis hypothesis by testing whether infections that were exogenous to Cologne or to Dusseldorf were endogenous to the greater region supported endogenous spread in MSM subjects and exogenous spread in the endemic transmission group. In intravenous drug using group subjects, it depended on viral strain, with subtype B sequences appearing to have origin exogenous to the Resina data, while non-B sequences (primarily subtype A) were almost completely endogenous to their local community. These results suggest that, at least in Germany, the question of endogenous versus exogenous linkages depends on subject group.Medical Microbiology and Immunology 01/2012; 201(3):259-69. DOI:10.1007/s00430-011-0228-8 · 3.04 Impact Factor
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ABSTRACT: For a long time, the clinical management of antiretroviral drug resistance was based on sequence analysis of the HIV genome followed by estimating drug susceptibility from the mutational pattern that was detected. The large number of anti-HIV drugs and HIV drug resistance mutations has prompted the development of computer-aided genotype interpretation systems, typically comprising rules handcrafted by experts via careful examination of in vitro and in vivo resistance data. More recently, machine learning approaches have been applied to establish data-driven engines able to indicate the most effective treatments for any patient and virus combination. Systems of this kind, currently including the Resistance Response Database Initiative and the EuResist engine, must learn from the large data sets of patient histories and can provide an objective and accurate estimate of the virological response to different antiretroviral regimens. The EuResist engine was developed by a European consortium of HIV and bioinformatics experts and compares favorably with the most commonly used genotype interpretation systems and HIV drug resistance experts. Next-generation treatment response prediction engines may valuably assist the HIV specialist in the challenging task of establishing effective regimens for patients harboring drug-resistant virus strains. The extensive collection and accurate processing of increasingly large patient data sets are eagerly awaited to further train and translate these systems from prototype engines into real-life treatment decision support tools.Intervirology 01/2012; 55(2):123-7. DOI:10.1159/000332008 · 1.68 Impact Factor
Article: Efficacy of Antiretroviral Therapy Switch in HIV-Infected Patients: A 10-Year Analysis of the EuResist Cohort[Show abstract] [Hide abstract]
ABSTRACT: Highly active antiretroviral therapy (HAART) has been shown to be effective in many recent trials. However, there is limited data on time trends of HAART efficacy after treatment change. Data from different European cohorts were compiled within the EuResist Project. The efficacy of HAART defined by suppression of viral replication at 24 weeks after therapy switch was analyzed considering previous treatment modifications from 1999 to 2008. Results: Altogether, 12,323 treatment change episodes in 7,342 patients were included in the analysis. In 1999, HAART after treatment switch was effective in 38.0% of the patients who had previously undergone 1-5 therapies. This figure rose to 85.0% in 2008. In patients with more than 5 previous therapies, efficacy rose from 23.9 to 76.2% in the same time period. In patients with detectable viral load at therapy switch, the efficacy rose from 23.3 to 66.7% with 1-5 previous treatments and from 14.4 to 55.6% with more than 5 previous treatments. The results of this large cohort show that the outcome of HAART switch has improved considerably over the last years. This result was particularly observed in the context after viral rebound. Thus, changing HAART is no longer associated with a high risk of treatment failure.Intervirology 01/2012; 55(2):160-6. DOI:10.1159/000332018 · 1.68 Impact Factor
Article: Mutational patterns in the frameshift-regulating site of HIV-1 selected by protease inhibitors[Show abstract] [Hide abstract]
ABSTRACT: Sustained suppression of viral replication in HIV-1 infected patients is especially hampered by the emergence of HIV-1 drug resistance. The mechanisms of drug resistance mainly involve mutations directly altering the interaction of viral enzymes and inhibitors. However, protease inhibitors do not only select for mutations in the protease but also for mutations in the precursor Gag and Pol proteins. In this study, we analysed the frameshift-regulating site of HIV-1 subtype B isolates, which also encodes for Gag and Pol proteins, classified as either treatment-naïve (TN) or protease inhibitor resistant (PI-R). HIV-1 Gag cleavage site mutations (G435E, K436N, I437V, L449F/V) especially correlated with protease inhibitor resistance mutations, but also Pol cleavage site mutations (D05G, D05S) could be assigned to specific protease resistance profiles. Additionally, two Gag non-cleavage site mutations (S440F, H441P) were observed more often in HIV-1 isolates carrying protease resistance mutations. However, in dual luciferase assays, the frameshift efficiencies of specific clones did not reveal any effect from these mutations. Nevertheless, two patterns of mutations modestly increased the frameshift rates in vitro, but were not specifically accumulating in PI-resistant HIV-1 isolates. In summary, HIV-1 Gag cleavage site mutations were dominantly selected in PI-resistant HIV-1 isolates but also Pol cleavage site mutations influenced resistance profiles in the protease. Additionally, Gag non-cleavage site mutations accumulated in PI-resistant HIV-1 isolates, but were not related to an increased frameshift efficiency.Medical Microbiology and Immunology 12/2011; 201(2):213-8. DOI:10.1007/s00430-011-0224-z · 3.04 Impact Factor
Article: Correction: Antiretroviral Therapy Optimisation without Genotype Resistance Testing: A Perspective on Treatment History Based Models[Show abstract] [Hide abstract]
ABSTRACT: [This corrects the article on p. e13753 in vol. 5.].PLoS ONE 04/2011; 6(4). DOI:10.1371/annotation/d0254103-21b9-4078-836b-57ba5bd1c26a · 3.23 Impact Factor
Article: The SnoB study: frequency of baseline raltegravir resistance mutations prevalence in different non-B subtypes[Show abstract] [Hide abstract]
ABSTRACT: The SnoB study analysed the variability of the integrase (IN) gene of non-B viruses from treatment-naïve patients to determine whether non-B subtypes carry natural resistance mutations to raltegravir (RAL). Plasma viral RNA from 427 patients was gained, and IN sequences were subtyped and screened for subtype-specific highly-variable residues. Seven viruses of different subtypes were phenotypically tested for RAL susceptibility; 359/427 samples could be sequenced. One hundred and seventy samples (47%) were classified as non-B subtypes. No primary RAL resistance-associated mutations (RRAMs) were detected. Certain secondary mutations were found, mostly related to specific non-B subtypes. L74 M was significantly more prevalent in subtype 02_AG, T97A in A and 06_cpx, V151I in 06_cpx, and G163R in 12_BF. Various additional mutations were also detected and could be associated with the subtype too. While K156 N and S230 N were correlated with B subtype, V72I, L74I, T112I, T125A, V201I and T206S were more frequent in certain non-B subtypes. The resistance factors (RF) of 7 viral strains of different subtypes ranged from 1.0 to 1.9. No primary or secondary but subtype-associated additional RRAMs were present. No correlation between RF and additional RRAMs was found. The prevalence of RRAMs was higher in non-B samples. However, the RFs for the analysed non-B subtypes showed lower values to those reported relevant to clinical failure. As the role of baseline secondary and additional mutations on RAL therapy failure is actually not known, baseline IN screening is necessary.Medical Microbiology and Immunology 04/2011; 200(4):225-32. DOI:10.1007/s00430-011-0194-1 · 3.04 Impact Factor
Article: Prediction of response to antiretroviral therapy by human experts and by the EuResist data-driven expert system (the EVE study)[Show abstract] [Hide abstract]
ABSTRACT: The EuResist expert system is a novel data-driven online system for computing the probability of 8-week success for any given pair of HIV-1 genotype and combination antiretroviral therapy regimen plus optional patient information. The objective of this study was to compare the EuResist system vs. human experts (EVE) for the ability to predict response to treatment. The EuResist system was compared with 10 HIV-1 drug resistance experts for the ability to predict 8-week response to 25 treatment cases derived from the EuResist database validation data set. All current and past patient data were made available to simulate clinical practice. The experts were asked to provide a qualitative and quantitative estimate of the probability of treatment success. There were 15 treatment successes and 10 treatment failures. In the classification task, the number of mislabelled cases was six for EuResist and 6-13 for the human experts [mean±standard deviation (SD) 9.1±1.9]. The accuracy of EuResist was higher than the average for the experts (0.76 vs. 0.64, respectively). The quantitative estimates computed by EuResist were significantly correlated (Pearson r=0.695, P<0.0001) with the mean quantitative estimates provided by the experts. However, the agreement among experts was only moderate (for the classification task, inter-rater κ=0.355; for the quantitative estimation, mean±SD coefficient of variation=55.9±22.4%). With this limited data set, the EuResist engine performed comparably to or better than human experts. The system warrants further investigation as a treatment-decision support tool in clinical practice.HIV Medicine 04/2011; 12(4):211-8. DOI:10.1111/j.1468-1293.2010.00871.x · 3.99 Impact Factor
Article: HIV prevalence and route of transmission in Turkish immigrants living in North-Rhine Westphalia, Germany[Show abstract] [Hide abstract]
ABSTRACT: The high number of Turkish immigrants in the German state North-Rhine Westphalia (NRW) compelled us to look for HIV-infected patients with Turkish nationality. In the AREVIR database, we found 127 (107 men, 20 women) Turkish HIV patients living in NRW. In order to investigate transmission clusters and their correlation to gender, nationality and self-reported transmission mode, a phylogenetic analysis including pol gene sequences was performed. Subtype distribution and the number of HIV drug resistance mutations in the Turkish patient group were found to be similar to the proportion in the non-Turkish patients. Great differences were observed in self-reported mode of transmission in the heterosexual Turkish male subgroup. Neighbour-joining tree of pol gene sequences gave indication that 59% of these reported heterosexual transmissions cluster with those of men having sex with men in the database. This is the first study analysing HIV type distribution, drug resistance mutations and transmission mode in a Turkish immigrant population.Medical Microbiology and Immunology 04/2011; 200(4):219-23. DOI:10.1007/s00430-011-0193-2 · 3.04 Impact Factor
Article: Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach[Show abstract] [Hide abstract]
ABSTRACT: Maraviroc (MVC) is the first licensed antiretroviral drug from the class of coreceptor antagonists. It binds to the host coreceptor CCR5, which is used by the majority of HIV strains in order to infect the human immune cells (Fig. 1). Other HIV isolates use a different coreceptor, the CXCR4. Which receptor is used, is determined in the virus by the Env protein (Fig. 2). Depending on the coreceptor used, the viruses are classified as R5 or X4, respectively. MVC binds to the CCR5 receptor inhibiting the entry of R5 viruses into the target cell. During the course of disease, X4 viruses may emerge and outgrow the R5 viruses. Determination of coreceptor usage (also called tropism) is therefore mandatory prior to administration of MVC, as demanded by EMA and FDA. The studies for MVC efficiency MOTIVATE, MERIT and 1029 have been performed with the Trofile assay from Monogram, San Francisco, U.S.A. This is a high quality assay based on sophisticated recombinant tests. The acceptance for this test for daily routine is rather low outside of the U.S.A., since the European physicians rather tend to work with decentralized expert laboratories, which also provide concomitant resistance testing. These laboratories have undergone several quality assurance evaluations, the last one being presented in 2011. For several years now, we have performed tropism determinations based on sequence analysis from the HIV env-V3 gene region (V3). This region carries enough information to perform a reliable prediction. The genotypic determination of coreceptor usage presents advantages such as: shorter turnover time (equivalent to resistance testing), lower costs, possibility to adapt the results to the patients' needs and possibility of analysing clinical samples with very low or even undetectable viral load (VL), particularly since the number of samples analysed with VL < 1000 copies/μl roughly increased in the last years (Fig. 3). The main steps for tropism testing (Fig. 4) demonstrated in this video: Collection of a blood sample Isolation of the HIV RNA from the plasma and/or HIV proviral DNA from blood mononuclear cells Amplification of the env region Amplification of the V3 region Sequence reaction of the V3 amplicon Purification of the sequencing samples Sequencing the purified samples Sequence editing Sequencing data interpretation and tropism prediction.Journal of Visualized Experiments 01/2011; 58(58). DOI:10.3791/3264 · 1.33 Impact Factor
Article: Antiretroviral Therapy Optimisation without Genotype Resistance Testing: A Perspective on Treatment History Based Models[Show abstract] [Hide abstract]
ABSTRACT: Although genotypic resistance testing (GRT) is recommended to guide combination antiretroviral therapy (cART), funding and/or facilities to perform GRT may not be available in low to middle income countries. Since treatment history (TH) impacts response to subsequent therapy, we investigated a set of statistical learning models to optimise cART in the absence of GRT information. The EuResist database was used to extract 8-week and 24-week treatment change episodes (TCE) with GRT and additional clinical, demographic and TH information. Random Forest (RF) classification was used to predict 8- and 24-week success, defined as undetectable HIV-1 RNA, comparing nested models including (i) GRT+TH and (ii) TH without GRT, using multiple cross-validation and area under the receiver operating characteristic curve (AUC). Virological success was achieved in 68.2% and 68.0% of TCE at 8- and 24-weeks (n = 2,831 and 2,579), respectively. RF (i) and (ii) showed comparable performances, with an average (st.dev.) AUC 0.77 (0.031) vs. 0.757 (0.035) at 8-weeks, 0.834 (0.027) vs. 0.821 (0.025) at 24-weeks. Sensitivity analyses, carried out on a data subset that included antiretroviral regimens commonly used in low to middle income countries, confirmed our findings. Training on subtype B and validation on non-B isolates resulted in a decline of performance for models (i) and (ii). Treatment history-based RF prediction models are comparable to GRT-based for classification of virological outcome. These results may be relevant for therapy optimisation in areas where availability of GRT is limited. Further investigations are required in order to account for different demographics, subtypes and different therapy switching strategies.PLoS ONE 10/2010; 5(10):e13753. DOI:10.1371/journal.pone.0013753 · 3.23 Impact Factor
Article: Evolution of protease inhibitor resistance in the gag and pol genes of HIV subtype G isolates[Show abstract] [Hide abstract]
ABSTRACT: To analyse HIV Gag cleavage site (CS) and non-CS mutations in HIV non-B isolates from patients failing antiretroviral therapy. Twenty-one HIV isolates were obtained from patients infected with HIV subtype G during an outbreak in Russia 20 years ago. Most patients were failing antiretroviral therapy when genotyping was performed. HIV Gag CS mutations accumulated in protease inhibitor (PI)-resistant HIV isolates and were correlated with the presence of three or more PI resistance mutations. Only 1 of 11 HIV isolates carrying major protease mutations did not harbour treatment-associated CS mutations. Natural polymorphism 453T, often found in HIV non-B subtypes, seems to favour the selection of CS mutation 453I rather than treatment-associated CS mutation 453L. Resistance-associated non-CS mutations (123E and 200I) were also observed in PI-resistant clinical isolates. Non-CS mutations in the frameshift-regulating site, which controls the synthesis of Gag-Pol, did not affect frameshift efficiency in dual luciferase assays. Of note, one of four HIV isolates from patients failing PI therapies without protease mutations harboured Gag mutations associated with PI resistance (123E and 436R) and reverse transcriptase inhibitor mutations conferring resistance to the backbone drug. HIV Gag CS mutations commonly occurred in HIV isolates from patients failing PI therapies and natural polymorphisms at the same position influence their emergence. Non-CS mutations previously associated with PI resistance were also observed in clinical isolates. Gag mutations might indicate the evolution of PI resistance even in the absence of protease mutations.Journal of Antimicrobial Chemotherapy 07/2010; 65(7):1472-6. DOI:10.1093/jac/dkq129 · 5.31 Impact Factor
Article: Transmission of Human Immunodeficiency Virus I Drug Resistance - a Case Report. What are the Clinical Implications?[Show abstract] [Hide abstract]
ABSTRACT: The success of first-line antiretroviral therapy can be challenged by the acquisition of primary drug resistance. Here we report a case where baseline genotypic resistance testing detected resistance conferring nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-associated mutations, but no primary mutations for protease inhibitor (PI). Subsequent PI-based HAART with boosted saquinavir led to virological treatment success with persistently undetectable viral load. After treatment simplification from saquinavir to an atazanavir based PI-therapy and no change in backbone therapy rapid virological breakthrough occurred. Retrospective analysis displayed preexisting gag cleavage site mutations which may have reduced the genetic barrier in a clinical relevant manner in combination with the already existing NRTI resistance mutations. Alternatively, this effect could be explained with a different antiviral potency for the respective PIs used.European journal of medical research 05/2010; 15(5):225-30. DOI:10.1186/2047-783X-15-5-225 · 1.50 Impact Factor
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University of Cologne
Köln, North Rhine-Westphalia, Germany
- Institute of Virology
Center of Advanced European Studies and ResearchBonn, North Rhine-Westphalia, Germany


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Honda CB 1100
Mixing naked and classic Honda style with thoroughly modern and engaging performance, the exquisitely built four-cylinder CB1100 has a presence, and personality, all of its own.
The Honda CB1100 mixes originality with a timeless sense of design, and substantial character. It represents a finely balanced blend of performance, with broad capacity, ability and adaptability.
Unmistakably Honda, the CB1100's clean lines elegantly echo the past. The large round headlight, scalloped fuel tank (proudly detailed with the Honda Wing) and silver painted sidepanels add style and substance, while familiar analog dials, slim seat, side-swept 4-2-1 exhaust pipe and chromed front and rear mudguards provide the finishing touches, gently stirring memories of how motorcycles used to look and, as importantly, feel.
Perhaps it's what you don't see that matters more with the CB1100; this is the motorcycle at its most elemental. A steel double cradle frame houses the engine, with 41mm conventional telescopic forks and twin rear shocks providing compliant and finely tuned suspension. The CB1100's riding position is upright and relaxed, a perfect platform from which to watch the world slide by.
From the outset of the project, the CB1100's development engineers decided to use the word 'design' rather than 'styling' for their new bike. Utilising the characteristics of many materials - metal, plastic, leather and rubber - they created individual parts that are both beautiful and functional, and bought them together to stunning effect.
Honda, as a company, looks to the future; yet always with one eye on, and great respect, for the past. To that end, the Honda CB1100 mixes originality with a timeless sense of design, and substantial character. It represents a finely balanced blend of performance, with broad capacity, ability and adaptability.
But it also has something else, almost an intangible - a small part of the soul of a true original: the Honda CB750 Four.
The CB750 Four has cast a long and influential shadow over motorcycling since its debut in 1969. Soichiro Honda, ever the engineer, leading an engineering company, wanted to prove that there was more to the two-wheeled formula than small and medium capacity twin-cylinder motorcycles, and did just that with the ground-breaking 749cc, 67bhp air-cooled, SOHC four-cylinder four-stroke power unit.
A competent chassis - with another first, a single disc brake up front - provided handling and stopping power to match the engine, and the CB750 Four was an instant success. The mass-production superbike had been born, the blueprint drawn for the future.
Motorcycling has changed a great deal over the last 5 decades since the very first CB - the Benly CB92 - was introduced. Motorcyclists themselves have changed too: while many still aspire to the ultimate performance available, just as many today perhaps have other reasons to own a motorcycle.
Some are looking back, at the bike they wanted when they were young but simply couldn't afford. Others want something that performs like a new machine, but with a certain, classic look that lends retro-heritage to a contemporary lifestyle.
And some riders just want an
exquisitely engineered motorcycle that blends real-world usability with an
honest sense of history. The common factor is fun.
Mr Mitsuyoshi Kohama, Chief Designer, CB1100
"It just had to be an air-cooled
There is something about an air-cooled engine - a feeling you simply can't get from the liquid-cooled engine in a high-performance bike. To me, a bike rider and a bike fan, a future without air-cooled engines just didn't seem right. And I was certain I wasn't the only one who felt this way!
Based on my sketch, this 'bike that defies logic and just demands to be ridden' became a reality. We displayed the CB Four concept model at the Tokyo Motor Show in 1999, and I was extremely thankful for the enthusiastic response it received there. In 2007, aiming to create a bike that fulfilled fans' vision even more fully, we displayed a new concept model at the Tokyo Motor Show, the CB1100F. Eventually, this concept model became the production model known as the CB1100.
That period from the late 1960s through the '70s was
the golden age of motorcycling in America, an era characterized by simpler bikes
and a market far less fragmented and specialized. Modern motorcycles are
categorized into so many different niches—and have become so tailored to a
singular purpose—that it makes you wonder what happened to the good ol'
Universal Japanese Motorcycle, like Honda's CB550-1100s of yesteryear.
Source Cycle World


text:
StartUpHire is the place to find JAVA DEVELOPER (SERVER SIDE) jobs. Review the list of JAVA DEVELOPER (SERVER SIDE) career opportunities to the left. These JAVA DEVELOPER (SERVER SIDE) jobs represent some of the most rewarding careers available.
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Responsibilities: ---No boundaries with this position?if hired, you can be located in San Diego or remote--- This role will write code and make stuff work at a company built around delivering quality software in the emergency notification and IT alerting9/1/2015 San Diego, CA Save This Job
Job Type: Full-Time Location: Belmont, CA Department: Engineering RingCentral provides cloud computing based business phone systems designed for today's mobile and distributed business world. The RingCentral technology platform eliminates the need for expensive and8/17/2015 Belmont, CA Save This Job
Responsibilities 1. Design and implement server-side code for mobile-based applications. 2. Design and develop technical foundation for robust high-volume production applications. Requirements 1. BS or MS in Computer Science or related technical discipline. 2. Extensive8/25/2015 San Francisco, CA Save This Job
Engineering New York, NY, United States THE POSITION This is a highly-visible role for a Scala or Java developer on our core engineering team. Our client-facing web apps -- Servo -- will be your primary focus, and you'll be part of a team with tremendous company support8/11/2015 New York, NY Save This Job
ID 2015-1933 Job Location US-CA-Sunnyvale Category Engineering Type Regular Full-Time More information about this job: Qualifications: You will be a great fit if you: Are tenacious, curious and collaborative Are a quick learner and have excellent communication skills Enjoy9/28/2015 Sunnyvale, CA Save This Job
Background Tradingscreen is the leading global provider of multi-broker, multi-asset class electronic trading solutions. An essential part of our business involves developing reliable and efficient trading connections between our trading systems and those of our buy-side and8/23/2015 New York, NY Save This Job
As a Java Server developer for Shaker, you will design and develop server-side code for web-based applications and the Shaker Platform. We are looking for experienced developer with a proven track record of delivering scalable and robust applications using web technologies. You9/1/2015 San Francisco, CA Save This Job
Redwood City, CA Company Description Are you an ambitious, competitive go-getter with a positive attitude? If so, we want to talk to you! Headquartered in Silicon Valley, Satmetrix develops software used by businesses of all sizes to measure and manage the Customer Experience8/25/2015 Redwood City, CA Save This Job
Full-Stack Developer: With interest in workflow and collaboration tools Engineering - San Mateo, California We are seeking a full stack developer with awareness and appreciation for all technologies related to the web. We value a keen excitement for the potential and the9/5/2015 San Mateo, CA Save This Job
Location:Irvine, CA Department:Research and Development Job Description Looking for an eager iOS developer, you will be part of a small team developing a suite of iOS apps that are an important component in the next generation of mobile communication products. You will interact9/1/2015 Irvine, CA Save This Job
Tracking Code 1993 Job Description At Silver Spring Networks, software engineering is the backbone of our Smart Grid and Internet of Things initiatives. Silver Spring Networks? enterprise software manages millions of devices for some of the biggest cities and utilities in the9/5/2015 Redwood City, CA Save This Job
Network Operations Campbell, California APPLY Description The Senior ServiceNow Administrator will be responsible for architecting, implementing and managing the ServiceNow instance for 24/7. Post Implementation, this includes being the first point of escalation within the8/25/2015 Campbell, CA Save This Job
Department Engineering Job Overview This position will work as a member of the Software Engineering team to develop and maintain all parts of the Pentaho Open Source Business Intelligence software suite. Qualified individuals must have a solid background in the fundamentals of8/3/2015 Orlando, FL Save This Job
Essential Duties and Responsibilities: Full lifecycle application development Designing, coding and debugging applications in various software languages Object-oriented Design and Analysis (OOA and OOD) Support, maintain and document software functionality Evaluate and identify8/23/2015 Mentor, OH Save This Job
"Local candidates only" Minerva is a leading provider of service and subscriber management solutions for the delivery of pay television and video entertainment services. By supporting a best of breed open ecosystem, the Minerva platform has been deployed by over 2909/17/2015 Alviso, CA Save This Job
Engineering Foster City, CA, United States As an UI focused Web Application Developer, your work will elegantly visualize the real-time performance of billions of online video streams per month, helping to improve the viewing experience for millions of viewers watching9/1/2015 Foster City, CA Save This Job
Engineering Foster City, CA, United States As an UI focused Web Application Developer, your work will elegantly visualize the real-time performance of billions of online video streams per month, helping to improve the viewing experience for millions of viewers watching9/1/2015 Foster City, CA Save This Job
Description MarkMonitor, the world leader in enterprise brand protection and a Thomson Reuters Intellectual Property & Science business, uses a SaaS delivery model to provide advanced technology and expertise that protects the revenues and reputations of the world's leading9/6/2015 San Francisco, CA Save This Job
Location:Irvine, CA Department:Research and Development Job Description You will be part of a small team developing a suite of Android apps that are an important component in the next generation of mobile communication products. You will interact with other app developers, as9/1/2015 Irvine, CA Save This Job


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StartUpHire is the place to find EXECUTIVE PROJECT MANAGER jobs. Review the list of EXECUTIVE PROJECT MANAGER career opportunities to the left. These EXECUTIVE PROJECT MANAGER jobs represent some of the most rewarding careers available.
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The Senior Project Manager is responsible for accomplishing project objectives by planning and evaluating project procedures and activities.10/12/2015 Ithaca, NY Save This Job
Noesis is looking for a Senior Agile Project Manager to help build a world-class lending platform that our partners and lenders use to promote, sell, and finance commercial building improvement projects.10/7/2015 Austin, TX Save This Job
Overview GlobeSherpa is a Portland, Oregon based software company that specializes in making mobile payments easy. We provide a secure, mobile payment and mobile ticketing platform for transit customers interested in moving to open payments, open data, and mobile fare collection8/11/2015 Portland, OR Save This Job
Boulder, CO LogRhythm is looking for an IS Project Manager that will be responsible for planning, requirements gathering and transitioning business needs to technical needs in conjunction with stakeholders to ensure delivery of technology solutions that meet the needs of our8/30/2015 Boulder, CO Save This Job
The Cradlepoint R&D team has built a world class, extensible router and cloud management solution platform for distributed enterprises and have an immediate need for an experienced R&D project manager to transform the API into an SDK and work with 3rd party partners to deliver10/5/2015 Boise, ID Save This Job
Job Type: Full-Time Employee Posting Date: September 2, 2015 Summary Lead the deployment of a results-driven, enterprise-wide scheduling initiative, which will provide visibility into program status, work in progress, and resource utilization. Drive comprehensive and continuous9/30/2015 Apple Valley, MN Save This Job
Job Type: Full-Time Employee Posting Date: September 2, 2015 Summary Lead the deployment of a results-driven, enterprise-wide scheduling initiative, which will provide visibility into program status, work in progress, and resource utilization. Drive comprehensive and continuous9/30/2015 Apple Valley, MN Save This Job
Summary The Enterprise Project Manager is responsible for aligning the Newmarket global services organizations with the needs of the customer. Role includes supporting the planning, managing and reporting for one or more corporate projects and is ultimately responsible for the9/28/2015 Portsmouth, NH Save This Job
Department:Corporate Strategy Location:CA - Pleasanton WD # / Job Code:864 Description Ellie Mae (NYSE:ELLI) is a leading provider of enterprise on-demand solutions, including an online network, software and services for the residential mortgage industry. Ellie Mae is leading9/18/2015 Pleasanton, CA Save This Job
Tracking Code 2096 Job Description SUMMARY: The Senior Project Manager manages internal and external development projects as well as commercial product support where needed. This position will provide project management oversight for all stages of projects, including9/5/2015 Menlo Park, CA Save This Job
At eHarmony, we've never shied away from big challenges. We came together in 2000 believing that with a mix of psychology and some cutting edge technology, we could create relationships that were happier, more fulfilling and enduring.9/19/2015 Los Angeles, CA Save This Job
Tracking Code 2042 Job Description This individual will lead all planning and deployment aspects of customer projects in a particular geographic area with focus on one or more clients. The PM may be the principal customer liaison and must be able to manage concurrent projects10/5/2015 Redwood City, CA Save This Job
Role Alianza is the leading provider of cloud voice platforms for cable MSOs, ISPs and telcos. We have helped over 50 service providers launch new services or dramatically improve their existing services. It's a new way to deliver voice service that untangles operators from the9/14/2015 Lindon, UT Save This Job
Client Services Petaluma, CA, United States Since 1995, MarketLive, Inc. (www.marketlive.com) has been the leading provider of eCommerce technology and services that help fast-growing companies successfully sell goods and services online. With MarketLive Customer Driven8/29/2015 Petaluma, CA Save This Job
Portland, ME Full Time Engineering Mid Level SHARE Who We Are Vets First Choice (VFC) is the nation's largest veterinary-partner pharmacy, providing vets and their clients with cost effective home delivery service of medications and food. VFC is licensed in all 508/9/2015 Portland, ME Save This Job
Portland, ME Full Time Software Engineering Mid Level SHARE Who We Are Vets First Choice (VFC) is the nation's largest veterinary-partner pharmacy, providing vets and their clients with cost effective home delivery service of medications and food. VFC is licensed in8/9/2015 Portland, ME Save This Job
Share this page Facebook!FacebookShare this page LinkedIn!LinkedInShare this page on Twitter!Twitter Location: Farmington Hills, Michigan The Delivery Project Manager will be responsible for planning, executing and delivering Redbend?s solution to its customers on schedule,9/15/2015 Detroit, MI Save This Job
Position Description The Project Manager/Instructional Designer (PM/ID) is responsible for managing individual and multiple projects from conception to completed approved courseware. The PM/ID is also responsible for the design, development, and production of innovative and8/23/2015 Tallahassee, FL Save This Job
ID 2015-2125 Job Location US-NY-Manhattan Posted Date 9/11/2015 More information about this job: About Everyday Health, Inc.: Everyday Health, Inc. (NYSE: EVDY) is a leading provider of digital health and wellness solutions. Everyday Health attracts a large and engaged10/1/2015 Manhattan, NY Save This Job
Date Posted6/3/2015 Job TypeContract Full-Time Position Id22356 Job Description Project Manager ? Direct Sales Business (New Residential Customers) Our Direct Sales Operations Team is seeking a Project Manager contractor to join us in our El Segundo, California location. This9/7/2015 El Segundo, CA Save This Job


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Memory Test by GRuV Memory Test - is a logic game for memory. Remember the sequence of lamps switching and try to repeat it! The sequence … 1,000+ downloads, Rating 3.29 (14) Free
BertoBlog by Berto Aplicación de #BertoBlog. Aquí encontraréis el mismo contenido que en la versión Web pero en su versión para móvil. Con … 500+ downloads, Rating 4.70 (37) $1.10
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Droid Talk by Akshat Kumar This fun application introduces a new concept that fools the human eyes to see letters in thin air.This app uses a pheno … 1,000+ downloads, Rating 2.40 (15) Free
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"la Caixa" by "la Caixa" A personalised app to suit your needs and which combines the "la Caixa" services for mobiles: - Access to Línea Abierta … 1,000,000+ downloads, Rating 3.85 (26204) Free
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I am a Senior Lecturer in Biomedical Ethics and Law at the Centre for Ethics in Medicine at the University of Bristol. From 2005- 2013 I worked at the University of Manchester's Centre for Social Ethics and Policy in the School of Law where I was a Lecturer in Bioethics and before that a Research Fellow in Bioethics and Law.
Here you will find details of the various aspects of my work, including my teaching, research, publications, and other related activities.
The main focus of my research has been the philosophical analysis of law and policy in medicine and the biosciences. This often includes elements of doctrinal legal analysis combined with matters of practical ethics, with an eye on the regulatory and social context in which scientific and medical innovation takes place. There is an explicit interdisciplinary influence on this which draws on insights gained from law and philosophy, as well as science and medicine.
One theme which recurs in my research is that of the human body. As such, much of my research has been at the intersection of the law, political and legal philosophy, and ethics as it pertains to property in the body and human biomaterials. The core of the research is an analysis of arguments pertaining to self-ownership and property rights in separated biomaterials, and how these fit within the common law as it currently stands.
Other research focuses on the idea of nudging. In particular I am interested in how research from the behavioural science is being (and could be) used in the legal, regulatory, and policy contexts; broadly construed this work involves looking at the regulation of health at state level and examining the normative legitimacy of a variety of health-affecting strategies and interventions.
My research interests are unified by a curiosity in biotechnological advances and innovations, especially how these can be and ought to be dealt with by society. As such, other research interests include the law and ethics of reproduction and the reproductive technologies, organ transplantation, rights, and public (health) policy. I have been involved in projects, organised and participated in conferences, and published papers on the law and ethics of organ donation, reproductive rights, enhancement, property and human tissue, public health, and the use of animals in research. You can find detailed information on my research activities here and my publications here.
A short interview about the ethical issues in synthetic biology for the SYBHEL project.


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National Security Threats
Generals James Mattis (Ret.), General John Keane (Ret.), and Admiral William Fallon (Ret.) testified at a Senate Armed Services committee hearing on threats to U.S. national…6,722 views
Generals James Mattis (Ret.), General John Keane (Ret.), and Admiral William Fallon (Ret.) testified at a Senate Armed Services committee hearing on threats to U.S. national…6,722 views
Former Ambassador to Iraq Ryan Crocker, former Marine Corps General Jim Mattis, and Dafna Rand testified on the ISIS* terrorist threat to the U.S. and other countries, and the stability of…2,306 views
Central and Special Operations Commands leaders testified on funding for 2014 military programs. General James Mattis, the head of military operations in the Middle East and Central…771 views
Witnesses testified on the U.S. Central and Special Operations Command fiscal year 2013 budget. They focused on political unrest and violence in Syria, Iran's nuclear program and…723 views
General James Mattis spoke at the 2012 Ottawa Conference on Defense and Security. He discussed the role of allied forces.545 views
General James Mattis, commander of the U.S. Central Command, gave the keynote address at the American Veterans Center Conference. He talked about the qualities of a good leader, the…1,351 views
General Mattis spoke about U.S. national security interests and challenges to national security in the Middle East. Among the topics he addressed were plans for troop withdrawals from…1,118 views
The commanders of U.S. Central Command and Special Operations testified before the House Armed Services Committee on the proposed fiscal year 2012 budget for military operation of the…315 views
Military leaders testified about U.S. military operations in Iraq and Afghanistan, as well as about conflict between government and anti-government forces in Libya. They said any…478 views


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Hyalite Equipment Classic AC
Where to Buy
sponsored links
Retailers' Descriptions
Here's what other sites are saying:
CLOSEOUTS . For the minimalist backpacker who doesnand#39;t like to sacrifice comfort, the Hyalite Equipment Classic AC sleeping pad is the durable top choice. Its small pack size fits easily into your bag and expands to a full-size sleeping mat to cradle you in comfort in the backcountry. Available Colors: DEEP WATER.
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For the budget conscious customer, the Classic AC sleeping pads fit the bill. Classic rectangle shaped Air Fill pad with a durable plastic valve Oversized outside tubes cradle user in the saddle to keep from shifting off the pad in the night 75D polyester top fabric and ripstop bottom for maximum durability DWR finish to help protect from stains and make pad water resistant Stuff sack, repair kit, and wrap strap included Item Specifications Color Light Blue Weight 535g Dimensions 20 x 66 x 2.5"
- Mountains Plus
Hyalite Equipment Classic AC
currently retails for:


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Mantra Mooloolaba Beach Resort
No prices found through our partners. Please contact the business directly or check some of our recommended alternatives.
How has this hotel rated in the past?
- Drycleaning onsite
- Meeting rooms/conference facilities
- Spa
- Laundry facilities (self serve)
- High-speed internet in room
- Heated pool
Travelers also recommend:
TripAdvisor Reviews Mantra Mooloolaba Beach Resort
Travel Blogs from Mooloolaba
More Glitz & Wind
... solar panels, bounced off the kayaks and ended up back in the ocean. Crazy.
Moreton Bay must be closed to ships with the strong wind as many ships are anchored alongside the shipping channel and there is no shipping movements. The closer we get to land the smoother the seas become and our speed picks up, mind you we have been travelling at 7.5knots since Cape Moreton. An hour out from Mooloolaba we are in the lee of the land and wind decreases, sea flattens ...
Day #13 (Sunday)
... were all on our own. Wanna guess what we did? Shopping! We walked around the town and entered nearly every store. Many backpackers stay over at Noosa so the area is surrounded with young people (and families). The weather has really spoiled us today since it had been pouring earlier this week and now it was perfect. We first went to a more "private" are of the beach which was we're all the surfers were. The shore area here was covered with rocks. Not long after did ...
Australia Zoo
... was fed by 16year old Bindi and Terri.
Overall the show was amazing and finished with a fantastic song/rap by Steve himself (trying to get a you tube link to it now). Superb.
After the show we made our way through the Roo and wallabies to the wetlands where various birds were enjoying themselves. We did the koala walk, getting good at spotting koalas sleeping in trees, stroked some red kangaroos and went through the rainforest aviary. The wombats ...
Day off tomorrow yipeee
Just as our 8th working day and getting up at 5 (4.30 today!) was coming to a close we received the wonderful news that we have tomorrow off as the plants aren't going to arrive in time for us to put in. So, no alarms are to be set, we are going to sit, have a glass of wine, then relax tomorrow before our Sunday roast with Gregg and the family. Beautiful! ...
Entering paradise / The Schoolie Experience
On the Saturday morning of our trip we ate a few items out of the interesting boxed breakfast that had been on the counter in our townhouses. The previous night when we were on our way to dinner, Carolyn reminded us to put the milk into the fridge so it would be nice and cool for the morning. To which the Canadians replied "why ISN'T IT in the fridge?"... interesting how different food regulations can be. Not saying it's wrong, just different! Speaking of which, we also saw ...


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Browsing Evidence Based Practice, 2012 (MU) by Title
Now showing items 131-150 of 205
Now showing items 131-150 of 205
|Should a 6-week-old infant exposed to chicken pox in a sibling receive varicella-zoster immune globulin (VZIG) or acyclovir? [1]
|Should a Cytobrush be used for Pap smears in pregnant patients? [1]
|Should all patients with type 2 diabetes be offered a statin medication? [1]
|Should caffeine be restricted during pregnancy? [1]
|Should we give anti-D immunoglobulin to Rh-negative women with first trimester bleeding? [1]
|Small effects [1]
|Solar advice [1]
|Under what circumstances should a patient with an anterior cruciate ligament tear undergo surgical repair? [1]
|Understanding GI issues [1]
|What antibody studies are helpful in the diagnosis of Hashimoto's thyroiditis? [1]
|What are the benefits and harms for chlamydia screening in asymptomatic men and women? [1]
|What are the benefits and harms of bedrest for complications of pregnancy? [1]
|What are the benefits of omega-3 fatty acid supplementation during pregnancy? [1]
|What are the benefits of treating subclinical hypothyroidism? [1]
|What are the causes of chronic perianal dermatitis in kids? [1]
|What are the long-term benefits of giving metformin to a patient with metabolic syndrome? [1]
|What are the long-term health consequences of childhood sexual abuse? [1]
|What are the most effective therapies for bronchiolitis? [1]
|What are the options for treating presumed benign ovarian cysts? [1]
|What are the risks of using atypical antipsychotic drugs in treating patients with neuropsychiatric symptoms of dementia? [1]


text:
A very old domain with great potential
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3 to 6 days
Free delivery when you spend over £75 (GBP).
Will be calculated at checkout
Little Black Dresses - Black
You must select a size
Lace dress by NOTION 1.3. Long sleeves and rounded neckline. Detailing in contrast material to top. Defined waist and concealed zipper with hook and eye to reverse. Hand wash recommended.
Made of 85% Polyester and 15% Spandex. Lining of 100% Polyester.
With simple, clean lines and a sophisticated color palette, NLY Designs ranks high on the trend meter. Scandinavia meets Paris and the result is minimalism with a hint of rock n' roll.
Free delivery when you spend over £75. Standard shipping £3.95. Delivery time: 3-6 days. We deliver with UPS.
No reviews have been written yet.


text:
Batman Jigsaw Puzzle Game
I Like This Game ( Liked by 7 people )
How to play Jigsaw Puzzle?
- Click and drag pieces to place them in the puzzle.
- Correct pieces when placed together will join together.
- Continue dragging pieces until the puzzle is finished.
- The faster you finish the puzzle, the higher your score will be.
Batman Jigsaw Puzzle Game DescriptionBatman, originally referred to as the Bat-Man and still referred to at times as the Batman , is a fictional character, a comic book superhero co-created by artist Bob Kane and writer Bill Finger (although only Kane receives official credit), appearing in publications by DC Comics. The character first appeared in Detective Comics #27 in May 1939.
Related Jigsaw Puzzle Games
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try it\r\n
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This is when Batman has to face all of his worst villains yet.
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Batman The Dark Knight Rises Jigsaw Puzzle
can you having high score
Difficulty: Hard


text:
Is not life a hundred times too short for us to bore ourselves?
Friedrich Nietzsche (1844 - 1900)
Contributed by: Zaady
My time has not yet come either; some are born posthumously.
Source: Ecce Homo, 1888
Wisdom sets bounds even to knowledge.
Before the effect one believes in different causes than one does afterward.
I tell you: one must have chaos in one to give birth to a dancing star. I tell you: you still have chaos in you.
It is certainly not the least charm of a theory that it is refutable.
People who have given us their complete confidence believe that they have a right to ours. The inference is false, a gift confers no rights.
Contentment preserves one from catching cold. Has a woman who knew that she was well dressed ever caught a cold? No, not even when she had scarcely a rag on her back.
Convictions are more dangerous enemies of the truth than lies.
As an artist, a man has no home in Europe save in Paris.
Copyright © 2015 Gaiam, Inc.


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4 bed detached house for sale
£695,000 Guide Price
Guide Price £695,000
15 bedroom hotel for sale Cley Hall High Street, Spalding, PE11Prominently located award winning 15 bedroom grade II listed Georgian Hotel with parking for 18 cars. Elegant public rooms, an attractive Owners' flat and a delightful walled garden. Excellent profits from a turnover circa £328k per annum.A 'Lifestyle business' with tremendous potential. More details ›
6 bedroom detached house for sale Woolram Wygate, Spalding, Lincolnshire, PE11Winkworth Estate Agents are delighted to offer for sale this truly stunning detached family home with over 5200 square feet of versatile accommodation that could easily be divided to incorporate a ground floor self contained annex. The property has been designed and extended by the (contd...) More details ›
Added on 03/09/2015 by Winkworth, Bourne. Call: 01778 776032 Local call rate
4 bedroom detached house for sale Beechfield Gardens, SpaldingMorriss and Mennie Estate Agents offer For Sale this bespoke and contemporary and detached family home, located in one of Spalding's most sought prestigious roads within walking distance to Spalding town centre offering a comprehensive range of shops, schools and amenities. The plot offe... More details ›
Added on 22/09/2015 by Morriss & Mennie Estate Agents, Spalding. Call: 03301 011738 Local call rate
£500,000 Guide Price
- 4
- 0
Guide Price £500,000
Retail Property (out of town) for sale Cowbit Road, SpaldingLarge three bedroom house with separate 10 room functioning MotelPotential for redevelopment subject to gaining the necessary Planning PermissionFor Sale by Private Treaty with Vacant Possession More details ›
Marketed by Brown & Co, Commercial. Call: 01553 403101 Local call rate
4 bedroom detached house for sale Pinchbeck Road, Spalding, Lincolnshire, PE11Winkworth Estate Agents are delighted to offer for sale this elegant grade II listed Victorian house with detached self-contained annex to the rear. The property offers huge potential for residential/commercial/combined usage and is located in one of Spalding's premier locations (contd...) More details ›
Reduced on 15/05/2015 by Winkworth, Bourne. Call: 01778 776032 Local call rate
5 bedroom detached house for sale SpaldingSedge Estate Agents are delighted to offer for sale this extensive period detached property, situated in one of Spalding's premier locations. This distinctive property boasts five double bedrooms, five reception rooms, mature frontage with in and out driveway, a substantially sized rear garden wh... More details ›
4 bedroom detached house for sale Tydd Road, West PinchbeckJobson Bridge Farm is a stunning family home in the heart of the countryside with open views. The property is a detached three/four bedroom farm house which was built in 1996 and is situated on a plot of 1.4 acres. The property boasts several barns which may have the possibility of dividing into ... More details ›
5 bedroom character property for sale London Road, SpaldingA stunning Grade II Listed Georgian townhouse overlooking the River Welland. The property has been renovated and restored to a high standard whilst retaining original features including restored shutters to sash windows, a Charles Yorke bespoke kitchen and original fireplaces. More details ›
5 bedroom town house for sale London Road, Spalding* Grade II Listed * Situated in a Conservation Area * Dining Room & Drawing Room * Family Bathroom & Two En Suites * Study * Walled rear garden with stone patio * Detached double garage More details ›
5 bedroom town house for sale London Road, Spalding, Lincolnshire, PE11This is old Spalding at its best, This grade II home located in the traditional market towns prestigious address of Upper Welland Terrace really has to be seen to be appreciated. With just under 3000 sq. feet over four floors with five bedrooms and two reception rooms. With the (contd...) More details ›
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Pussycat Dolls singer Nicole Scherzinger and racing driver Lewis Hamilton have just announced that they are back together just a month or so after their big split! Nicole says they never fell out of love with each other and the only reason for the break-up was their heavy schedules. So they have come up with a 4-point plan to save their relationship! Here are the couples new rules:
1. No phonecalls during romantic dinners. Both Nicole and Lewis have promised to turn off their phones while they are dining out
2. No reading tabloid stories about each other!
3. They promise to speak to each other every day, not just to text or mail
4. Nicole has rescheduled her diary to spend more time with Lewis and make more time for romance!
We hope this new plan works out for them! (Source: Hello!)


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Tags: Iran, nukes, Rouhani
Sea Control 19 – Rouhani, Nukes, and Iran
January 2014
By LT Matthew Hipple
Benham Talebleu joins us to discuss Iran's new President, their nuclear weapons program, and the larger strategic aims of the Islamic Republic. Remember to subscribe on Itunes or Stitcher Stream radio! Leave a comment and a five-star rating before telling all your friends.
Please enjoy Sea Control 19: Rouhani, Nukes, and Iran (download).
Posted by LT Matthew Hipple in Foreign Policy, Maritime Security, Podcasts, Soft Power
Tags: Iran, nukes, Rouhani
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text: Fire restrictions Getty Images owens [ BLM Imposes Fire Restrictions For Natrona, Converse, Platte, Goshen Counties By Tom Morton August 4, 2015 The U.S. Bureau of Land Management, citing dry conditions and high fire danger, has placed partial fire restrictions on public lands it administers in Natrona, Converse, Platte and Goshen counties beginning today... Read More|Comment Category: Casper News, Wyoming News Tags: Converse County, fire restrictions, goshen county, Natrona County, Platte County, U.S. Bureau of Land Management Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!