Correlation between compartmental tenofovir concentrations and an ex vivo rectal biopsy model of tissue infectibility in the RMP-02/MTN-006 phase 1 study

Design: Phase 1, randomized, two-site (US), double-blind, placebo-controlled study of sexually-abstinent males and females

Modelling height in adolescence: a comparison of methods for estimating the age at peak height velocity

Background: Controlling for maturational status and timing is crucial in lifecourse epidemiology. One popular non-invasive measure of maturity is the age at peak height velocity (PHV). There are several ways to estimate age at PHV, but it is unclear which of these to use in practice. Aim: To find the optimal approach for estimating age at PHV. Subjects and methods: Methods included the Preece & Baines non-linear growth model, multi-level models with fractional polynomials, SuperImposition by Translation And Rotation (SITAR) and functional data analysis. These were compared through a simulation study and using data from a large cohort of adolescent boys from the Christ’s Hospital School. Results: The SITAR model gave close to unbiased estimates of age at PHV, but convergence issues arose when measurement error was large. Preece & Baines achieved close to unbiased estimates, but shares similarity with the data generation model for our simulation study and was also computationally inefficient, taking 24 hours to fit the data from Christ’s Hospital School. Functional data analysis consistently converged, but had higher mean bias than SITAR. Almost all methods demonstrated strong correlations (r > 0.9) between true and estimated age at PHV. Conclusions: Both SITAR or the PBGM are useful models for adolescent growth and provide unbiased estimates of age at peak height velocity. Care should be taken as substantial bias and variance can occur with large measurement error

Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

Exploring local knowledge and perceptions on zoonoses among pastoralists in northern and eastern Tanzania

Background: Zoonoses account for the most commonly reported emerging and re-emerging infectious diseases in Sub-Saharan Africa. However, there is limited knowledge on how pastoral communities perceive zoonoses in relation to their livelihoods, culture and their wider ecology. This study was carried out to explore local knowledge and perceptions on zoonoses among pastoralists in Tanzania. Methodology and principal findings: This study involved pastoralists in Ngorongoro district in northern Tanzania and Kibaha and Bagamoyo districts in eastern Tanzania. Qualitative methods of focus group discussions, participatory epidemiology and interviews were used. A total of 223 people were involved in the study. Among the pastoralists, there was no specific term in their local language that describes zoonosis. Pastoralists from northern Tanzania possessed a higher understanding on the existence of a number of zoonoses than their eastern districts' counterparts. Understanding of zoonoses could be categorized into two broad groups: a local syndromic framework, whereby specific symptoms of a particular illness in humans concurred with symptoms in animals, and the biomedical framework, where a case definition is supported by diagnostic tests. Some pastoralists understand the possibility of some infections that could cross over to humans from animals but harm from these are generally tolerated and are not considered as threats. A number of social and cultural practices aimed at maintaining specific cultural functions including social cohesion and rites of passage involve animal products, which present zoonotic risk. Conclusions: These findings show how zoonoses are locally understood, and how epidemiology and biomedicine are shaping pastoralists perceptions to zoonoses. Evidence is needed to understand better the true burden and impact of zoonoses in these communities. More studies are needed that seek to clarify the common understanding of zoonoses that could be used to guide effective and locally relevant interventions. Such studies should consider in their approaches the pastoralists' wider social, cultural and economic set up

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity

BACKGROUND: The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals. METHODS: In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level-dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week. RESULTS: Marked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects. CONCLUSIONS: The MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug's characteristic subjective effects arise from its modulation of spontaneous brain activity.This research was supported by funds provided by the British public service broadcast station Channel 4 and was performed as part of a Beckley Foundation–Imperial College research program. KM is supported by the Wellcome Trust. RLC-H would like thank Yvonne Lewis, Awet Tewolde, Rosie Lees, Malgorzata Nike, and Renegade Pictures. Screenings for this research were performed at the NIHR/Wellcome Trust Imperial Clinical Research Facility

Malaria and anemia prevention in pregnant women of rural Burkina Faso

BACKGROUND: Pregnant women are a major risk group for malaria in endemic areas. Only little information exists on the compliance of pregnant women with malaria and anaemia preventive drug regimens in the rural areas of sub-Saharan Africa (SSA). In this study, we collected information on malaria and anaemia prevention behaviour in pregnant women of rural Burkina Faso. METHODS: Cross-sectional qualitative and quantitative survey among 225 women of eight villages in rural northwestern Burkina Faso. Four of the villages had a health centre offering antenatal care (ANC) services while the other four were more than five kilometers away from a health centre. RESULTS: Overall ANC coverage (at least one visit) was 71% (95% in health centre villages vs 50% in remote villages). Malaria and anaemia were considered as the biggest problems during pregnancy in this community. ANC using women were quite satisfied with the quality of services, and compliance with malaria and anaemia prevention regimens (chloroquine and iron/folic acid) was high in this population. Knowledge on the benefit of bed nets and good nutrition was less prominent. Distance, lack of money and ignorance were the main reasons for women to not attend ANC services. CONCLUSIONS: There is an urgent need to improve access of rural SSA women to ANC services, either through increasing the number of rural health centres or establishing functioning outreach services. Moreover, alternative malaria and anaemia prevention programmes such as intermittent preventive treatment with effective antimalarials and the distribution of insecticide-treated bed nets need to become implemented on a large scale

Cooperative object transport with a swarm of e-puck robots: robustness and scalability of evolved collective strategies

Cooperative object transport in distributed multi-robot systems requires the coordination and synchronisation of pushing/pulling forces by a group of autonomous robots in order to transport items that cannot be transported by a single agent. The results of this study show that fairly robust and scalable collective transport strategies can be generated by robots equipped with a relatively simple sensory apparatus (i.e. no force sensors and no devices for direct communication). In the experiments described in this paper, homogeneous groups of physical e-puck robots are required to coordinate and synchronise their actions in order to transport a heavy rectangular cuboid object as far as possible from its starting position to an arbitrary direction. The robots are controlled by dynamic neural networks synthesised using evolutionary computation techniques. The best evolved controller demonstrates an effective group transport strategy that is robust to variability in the physical characteristics of the object (i.e. object mass and size of the longest object’s side) and scalable to different group sizes. To run these experiments, we designed, built, and mounted on the robots a new sensor that returns the agents’ displacement on a 2D plane. The study shows that the feedback generated by the robots’ sensors relative to the object’s movement is sufficient to allow the robots to coordinate their efforts and to sustain the transports for an extended period of time. By extensively analysing successful behavioural strategies, we illustrate the nature of the operational mechanisms underpinning the coordination and synchronisation of actions during group transport

CP-31398, a putative p53-stabilizing molecule tested in mammalian cells and in yeast for its effects on p53 transcriptional activity

BACKGROUND: CP-31398 is a small molecule that has been reported to stabilize the DNA-binding core domain of the human tumor suppressor protein p53 in vitro. The compound was also reported to function as a potential anti-cancer drug by rescuing the DNA-binding activity and, consequently, the transcription activation function of mutant p53 protein in mammalian tissue culture cells and in mice. RESULTS: We performed a series of gene expression experiments to test the activity of CP-31398 in yeast and in human cell cultures. With these cell-based assays, we were unable to detect any specific stimulation of mutant p53 activity by this compound. Concentrations of CP-31398 that were reported to be active in the published work were highly toxic to the human H1299 lung carcinoma and Saos-2 cell lines in our experiments. CONCLUSION: In our experiments, the small molecule CP-31398 was unable to reactivate mutant p53 protein. The results of our in vivo experiments are in agreement with the recently published biochemical analysis of CP-31398 showing that this molecule does not bind p53 as previously claimed, but intercalates into DNA

Study of mass and momentum transfer in diesel sprays base on X-ray mass distribution measurements and on a theoretical derivation

[EN] In this paper, a research aimed at quantifying mass and momentum transfer in the near-nozzle field of diesel sprays injected into stagnant ambient air is reported. The study combines X-ray measurements for two different nozzles and axial positions, which provide mass distributions in the spray, with a theoretical model based on momentum flux conservation, which was previously validated. This investigation has allowed the validation of Gaussian profiles for local fuel concentration and velocity near the nozzle exit, as well as the determination of Schmidt number at realistic diesel spray conditions. 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