1,970 research outputs found
Comparing highly efficacious antimalarial drugs.
No full textColin Sutherland discusses a Policy Forum article that explores the design and standardization of pre-licensure phase III antimalarial treatment trials
The Flip-side of Cytoadherence: Immune Selection, Antigenic Variation and the var Genes of Plasmodium falciparum.
No full textIn areas where Plasmodium falciparum is endemic, the natural immunity acquired by people exposed to frequent malaria infection is likely to have a differential selective impact upon different parasite genotypes. It has been suggested that the immune response directed against the variant antigen PfEMP1, which is expressed on the infected erythrocyte surface, is a crucial determinant of parasite population structure and favours the existence of distinct strains, or Varotypes. Here, Colin Sutherland summarizes current knowledge of the var multigene family, which encodes the PfEMP1 variants, and suggests that this information may allow certain predictions of the strain hypothesis to be tested directly
Maneuvering performance in the colonial siphonophore, Nanomia bijuga
No full text© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sutherland, K. R., Gemmell, B. J., Colin, S. P., & Costello, J. H. Maneuvering performance in the colonial siphonophore, Nanomia bijuga. Biomimetics, 4(3), (2019): 62, doi:10.3390/biomimetics4030062.The colonial cnidarian, Nanomia bijuga, is highly proficient at moving in three-dimensional space through forward swimming, reverse swimming and turning. We used high speed videography, particle tracking, and particle image velocimetry (PIV) with frame rates up to 6400 s−1 to study the kinematics and fluid mechanics of N. bijuga during turning and reversing. N. bijuga achieved turns with high maneuverability (mean length–specific turning radius, R/L = 0.15 ± 0.10) and agility (mean angular velocity, ω = 104 ± 41 deg. s−1). The maximum angular velocity of N. bijuga, 215 deg. s−1, exceeded that of many vertebrates with more complex body forms and neurocircuitry. Through the combination of rapid nectophore contraction and velum modulation, N. bijuga generated high speed, narrow jets (maximum = 1063 ± 176 mm s−1; 295 nectophore lengths s−1) and thrust vectoring, which enabled high speed reverse swimming (maximum = 134 ± 28 mm s−1; 37 nectophore lengths s−1) that matched previously reported forward swimming speeds. A 1:1 ratio of forward to reverse swimming speed has not been recorded in other swimming organisms. Taken together, the colonial architecture, simple neurocircuitry, and tightly controlled pulsed jets by N. bijuga allow for a diverse repertoire of movements. Considering the further advantages of scalability and redundancy in colonies, N. bijuga is a model system for informing underwater propulsion and navigation of complex environments.This research was funded by the National Science Foundation (NSF) 1829932 and 173764 to K.R.S., NSF 1830015, 1536672, 1511721 to J.H.C., 1455440, 1536688, 1829913 to S.P.C., NSF 1511996 to B.J.G
A ctenophore (comb jelly) employs vortex rebound dynamics and outperforms other gelatinous swimmers
No full text© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gemmell, B. J., Colin, S. P., Costello, J. H., & Sutherland, K. R. (2019). A ctenophore (comb jelly) employs vortex rebound dynamics and outperforms other gelatinous swimmers. Royal Society Open Science, 6(3), (2019):181615, doi:10.1098/rsos.181615.Gelatinous zooplankton exhibit a wide range of propulsive swimming modes. One of the most energetically efficient is the rowing behaviour exhibited by many species of schyphomedusae, which employ vortex interactions to achieve this result. Ctenophores (comb jellies) typically use a slow swimming, cilia-based mode of propulsion. However, species within the genus Ocyropsis have developed an additional propulsive strategy of rowing the lobes, which are normally used for feeding, in order to rapidly escape from predators. In this study, we used high-speed digital particle image velocimetry to examine the kinematics and fluid dynamics of this rarely studied propulsive mechanism. This mechanism allows Ocyropsis to achieve size-adjusted speeds that are nearly double those of other large gelatinous swimmers. The investigation of the fluid dynamic basis of this escape mode reveals novel vortex interactions that have not previously been described for other biological propulsion systems. The arrangement of vortices during escape swimming produces a similar configuration and impact as that of the well-studied ‘vortex rebound’ phenomenon which occurs when a vortex ring approaches a solid wall. These results extend our understanding of how animals use vortex–vortex interactions and provide important insights that can inform the bioinspired engineering of propulsion systems.This research was supported by the grants from the National Science Foundation UNS-1511996 and IDBR-1455471 to B.J.G., S.P.C. and J.H.C. as well as OCE-1829945 to B.J.G., S.P.C., J.H.C. and K.R.S
Use of artemether-lumefantrine in the treatment of asymptomatic-malaria infection in HIV-positive and HIVnegative Nigerian adults.
No full textMalaria /HIV co-infection is a major challenge to public health in developing countries and yet
potential drug-drug interactions between antimalarial and antiviral regimens have not been
adequately investigated in people with both HIV and Plasmodium falciparum infections. Earlier
studies on the use of artemether-lumefantrine (AL) in Nigeria have neither addressed its use in
HIV-positive subjects nor in asymptomatic-malaria infection.
The present study investigated associations between drug resistant P. falciparum and the use
of medication for HIV management, drug-drug interactions between artemether-lumefantrine
and antiretroviral drugs (ARV) and the molecular markers of artemether-lumefantrine and
other antimalarial drugs.
Results of the study revealed an elevated day 7 lumefantrine concentrations in HIV subjects on
nevirapine treatment compared to their HIV-negative counterparts. Associations between
elevated day 7 levels of lumefantrine and the persistent parasitaemia could not be evaluated
due to inadequate power. Genetic analysis by DNA sequence of P. falciparum isolates revealed
strong selection for the pfmdr1codon86N allele among all treated individuals. This
polymorphism is a strong indicator of AL treatment failure or slow clearance in vivo. There was
a 72.6% prevalence of the pfcrt76T mutations in the population and this was observed to be
higher in the HIV-positive subjects. Three new mutations F73S, S97L and G165R were detected
on the pfmdr1 gene and the first case S436F mutation on the pfdhps gene to be reported in
Nigeria. The dhpsK540E and dhfrI164L mutations, associated with high-level resistance to
sulfadoxine-pyrimethamine (SP) were not observed in our small sample size.
The study also revealed that HIV-positive subjects were more likely to harbour parasites, at a
higher density, before and after treatment. Improvement of the immune status of HIV-infected
patients was suggested by the increase of CD4 cell count level in about 68% of the HIV-positive
patients.
This is a preliminary study and first of its kind to investigate drug-drug interactions between
ARVs and the antimalarial drug AL in HIV-positive patients co-infected with P. falciparum in
relation to parasite clearance. The findings of the study are very important but more work is
urgently needed with a larger sample size to confirm these findings
Vascular healing : cell biology and rheologic factors
No full textIssued as Progress report summary, Project E-25-M44 (continued by E-25-M80)Progress report summary has author: Colin J. Schwart
Vascular healing : cell biology and rheologic factors
No full textIssued as Progress report summary, Project no. E-25-M80 (continued by E-25-M44; continues E-25-614)Progress report summary has author: Colin J. Schwart
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'A daughter come home?': the travel writings of Colleen J. McElroy
No full textArtemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda.
No full textBackgroundUganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission.Methodology/principal findingsPatients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0-28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI -0.2-7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated.Conclusions/significanceDP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda.Trial registrationControlled-Trials.com ISRCTN75606663
Orbit design for future SpaceChip swarm missions in a planetary atmosphere
No full textThe effect of solar radiation pressure and atmospheric drag on the orbital dynamics of satellites-on-a-chip (SpaceChips) is exploited to design equatorial long-lived orbits about the oblate Earth. The orbit energy gain due to asymmetric solar radiation pressure, considering the Earth's shadow, is used to balance the energy loss due to atmospheric drag. Future missions for a swarm of SpaceChips are proposed, where a number of small devices are released from a conventional spacecraft to perform spatially distributed measurements of the conditions in the ionosphere and exosphere. It is shown that the orbit lifetime can be extended and indeed selected through solar radiation pressure and the end-of-life re-entry of the swarm can be ensured, by exploiting atmospheric drag
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