Artemisinin-induced parasite dormancy : a plausible mechanism for treatment failure

Background Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance. Methods In this study, an existing P. falciparum infection model is modified to incorporate the hypothesis of dormancy. Published in vitro data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment. Results The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials. Conclusions Although further studies are required to confirm dormancy in vivo, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.

Artemisinin induced dormancy in Plasmodium falciparum : duration, recovery rates and implications in treatment failure

Background Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Methods Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days. Results Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an ∼10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover. Conclusions These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.

Mode switching DFIG for low voltage ride through

With the rapid development of world-wide wind energy generation using doubly fed induction generations (DFIGs), low voltage ride through (LVRT) has become a great concern. This paper focuses on a unique topology of DFIG called IG connection mode to help the DFIG ride through grid faults smoothly. Transient analysis of IG connection mode is carried out to derive the generator currents. With this analysis, the control strategy for IG connection mode DFIG was developed. From the simulation results, it is clearly visible that IG mode could work in both normal and low grid voltage conditions. Simulation results clearly show that the DFIG with the proposed mode switching control could smoothly ride through low voltage grid faults while satisfying grid code requirements.

Design of mode switching scheme for low-voltage ride-through of doubly fed induction generators

A mode switching doubly fed induction generator (MSDFIG) scheme is proposed for the purpose of achieving low-voltage ride-through for wind turbines. The MSDFIG operates as a doubly fed induction generator (DFIG) under normal condition but upon the detection of a low-voltage incident, the generator is to smoothly transfer to operate under the induction generator mode through the switching in of a set of stator-side crowbar. The MSDFIG automatically reverts back to the DFIG mode when network voltage recovers. A new strategy on the control of the crowbar resistance is included. Analysis shows that the proposed MSDFIG scheme can ride through the complete low-voltage and voltage recovery stages. Effectiveness of the scheme is demonstrated through simulation and experiment studies.

Iron(II) spin transition complexes with dendritic ligands, Part I

The ligands G1- and G2-oligo (benzyl ether) (PBE) dendrons and their iron(II) complexes [Fe(Gn-PBE)3]A2·xH2O (with n = 1, 2 and A = triflate, tosylate) were prepared. The magnetic properties of the complexes were investigated by a SQUID magnetometer. All complexes exhibit gradual spin transition below room temperature. At very low temperatures the magnetic behaviour reflects zero-field splitting (ZFS) effects. 57Fe-Mössbauer spectroscopy was performed to distinguish between ZFS of high spin species and spin state conversion into the low spin state. Further characterisation was carried out by thermogravimetric analysis (TGA) and FT-IR spectroscopy. Structural features have been determined by powder XRD measurements.

Iron(II) spin-transition complexes with dendritic ligands, part II

The dendritic triazole-based complexes \[Fe(G1-BOC)3](triflate) 2·xH2O (1; G1-BOC = tert-butyl {3-\[3-(3-tert- butoxycarbonylaminopropyl)-5-(\[1,2,4]triazol-4-ylcarbamoyl)-phenyl]propyl} carbamate, triflate = CF3SO3-), \[Fe(G1-BOC) 3]-(tosylate)2·xH2O(2;tosylate = p-CH3PhSO3-),\[Fe(G1-DPBE)3]-(triflate) 2·xH2O {3; G1-DPBE = 3,5-bis(3,5- didodecaoxybenzyloxy)-N-\[1,2,4]triazol-4-ylbenzamide}, \[Fe(G1-DPBE) 3]-(tosylate)2·xH2O (4) and \[Fe(G1-DPBE)3](BF4)2·xH2O (5) were designed and synthesized. Magnetic and thermal properties of these novel complexes were characterized by magnetic susceptibility measurements, 57Fe Mössbauer spectroscopy and thermogravimetric analysis or differential scanning calorimetry, respectively. All dendritic complexes under study show different spin-transition behaviour with respect to the nature of different dendritic ligands and counteranions. Complexes 1 and 2 have pronounced effects of a spin-state change during the first heating process and gradual spintransition properties for further temperature treatments, whereas 3 and 4 exhibited a very sharp spin-state change in the first heating procedures. Complex 5 showed a gradual spin-transition curve. In this paper, we report how the magnetic properties of these complexes are correlated with noncoordinated water molecules and their effects on spin states.

Integrating the impact of climate into event based failure models for water pipes

This paper presents an event-based failure model to predict the number of failures that occur in water distribution assets. Often, such models have been based on analysis of historical failure data combined with pipe characteristics and environmental conditions. In this paper weather data have been added to the model to take into account the commonly observed seasonal variation of the failure rate. The theoretical basis of existing logistic regression models is briefly described in this paper, along with the refinements made to the model for inclusion of seasonal variation of weather. The performance of these refinements is tested using data from two Australian water authorities.

Seasonal factors influencing the failure of buried water reticulation pipes

While the use of environmental factors in the analysis and prediction of failures of buried reticulation pipes in cold environments has been the focus of extensive work, the same cannot be said for failures occurring on pipes in other (non-freezing) environments. A novel analysis of pipe failures in such an environment is the subject of this paper. An exploratory statistical analysis was undertaken, identifying a peak in failure rates during mid to late summer. This peak was found to correspond to a peak in the rate of circumferential failures, whilst the rate of longitudinal failures remained constant. Investigation into the effect of climate on failure rates revealed that the peak in failure rates occurs due to differential soil movement as the result of shrinkage in expansive soils.

Understanding how the Australian climate can affect pipe failure

This paper details a statistical analysis of historical failure data, which focuses on determining the manner in which local climate affects pipe failure rates. It was found that seasonality exists in the data, indicating an affect of local climate on failure rate. Significant variation in failure rates was seen between the months of December and May, especially in February/March, whilst limited variations were seen in other months of the year. Further analysis found that failure rates were strongly correlated with minimum antecedent precipitation index and net evaporation and that climate affected failure rate by influencing soil moisture content. Interaction affects between static attributes of the pipe-environment system and local climate were also investigated.

Transition Pedagogy Handbook : A Good Practice Guide for Policy and Practice in the First Year Experience at QUT

This Handbook has been specifically designed for academic and professional staff responsible for managing first year students and curriculum and co-curricular programs at QUT. As well as presenting examples of good practice, the handbook provides a brief overview of QUT’s First Year Experience Program, a summary of QUT’s First Year Experience and Retention Policy and the Transition Pedagogy that frames both curricular and co-curricular activities. We hope you find this resource both useful and informative.