Plasmodium vivax Sub-Patent Infections after Radical Treatment Are Common in Peruvian Patients: Results of a 1-Year Prospective Cohort Study

BACKGROUND: There is an increasing body of literature reporting treatment failure of the currently recommended radical treatment of Plasmodium vivax infections. As P. vivax is the main malaria species outside the African continent, emerging tolerance to its radical treatment regime could have major consequences in countries like Peru, where 80% of malaria cases are due to P. vivax. Here we describe the results of a 1-year longitudinal follow up of 51 confirmed P. vivax patients living around Iquitos, Peruvian Amazon, and treated according to the Peruvian national guidelines. METHODOLOGY: Each month a blood sample for microscopy and later genotyping was systematically collected. Recent exposure to infection was estimated by detecting antibodies against the P. vivax circumsporozoite protein (CSP) and all PCR confirmed P. vivax infections were genotyped with 16 polymorphic microsatellites. RESULTS: During a 1-year period, 84 recurrent infections, 22 positive also by microscopy, were identified, with a median survival time to first recurrent infection of 203 days. Most of them (71%) were asymptomatic; in 13 patients the infection persisted undetected by microscopy for several consecutive months. The genotype of mostly recurrent infections differed from that at day 0 while fewer differences were seen between the recurrent infections. The average expected heterozygosity was 0.56. There was strong linkage disequilibrium (I(A) (s) = 0.29, p<1.10(-4)) that remained also when analyzing only the unique haplotypes, suggesting common inbreeding. CONCLUSION: In Peru, the P. vivax recurrent infections were common and displayed a high turnover of parasite genotypes compared to day 0. Plasmodium vivax patients, even when treated according to the national guidelines, may still represent an important parasite reservoir that can maintain transmission. Any elimination effort should consider such a hidden reservoir

More than one way of being a moa: differences in leg bone robustness map divergent evolutionary trajectories in Dinornithidae and Emeidae (Dinornithiformes).

The extinct moa of New Zealand included three families (Megalapterygidae; Dinornithidae; Emeidae) of flightless palaeognath bird, ranging in mass from 200 kg. They are perceived to have evolved extremely robust leg bones, yet current estimates of body mass have very wide confidence intervals. Without reliable estimators of mass, the extent to which dinornithid and emeid hindlimbs were more robust than modern species remains unclear. Using the convex hull volumetric-based method on CT-scanned skeletons, we estimate the mass of a female Dinornis robustus (Dinornithidae) at 196 kg (range 155-245 kg) and of a female Pachyornis australis (Emeidae) as 50 kg (range 33-68 kg). Finite element analysis of CT-scanned femora and tibiotarsi of two moa and six species of modern palaeognath showed that P. australis experienced the lowest values for stress under all loading conditions, confirming it to be highly robust. In contrast, stress values in the femur of D. robustus were similar to those of modern flightless birds, whereas the tibiotarsus experienced the highest level of stress of any palaeognath. We consider that these two families of Dinornithiformes diverged in their biomechanical responses to selection for robustness and mobility, and exaggerated hindlimb strength was not the only successful evolutionary pathway

Epidermal growth factor and its influencing variables in healthy children and adults.

BACKGROUND & OBJECTIVE:Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations. METHODS:Both healthy adults (n = 50) and children (n = 78) were included. Serum and urinary EGF concentrations were measured with ELISA technology. RESULTS:Serum EGF was inversely correlated with age (r = -0.873; p<0.001) and positively correlated with serum magnesium (r = 0.597; p<0.001). The urinary EGF was also inversely correlated with age (r = -0.855; p<0.001). In adults and children older than 13 years of age, the urinary EGF significantly differed between sexes (p = 0.001). Urinary EGF was positively correlated with serum magnesium (r = 0.583; p<0.001) and creatinine clearance (r = 0.524; p<0.001) and negatively correlated with the fractional excretion of magnesium (r = 0.248; p = 0.014). In a multivariate model, age and serum magnesium remained independently related to serum EGF while age, serum EGF and serum magnesium remained independently related to urinary EGF. CONCLUSIONS:This study provides valuable insights in urinary and serum EGF patterns in healthy subjects. By systematically correcting EGF for body surface, significant correlations with age, gender and magnesium were observed

Finite element analysis results.

<p>Combined compression-bending results for the femur (a) and tibiotarsus (b). Values represent maximum von Mises stress (Pa) recorded at the midshaft of the bone. Pink and blue shaded areas represent the range of stress values estimated by finite element analysis when incorporating maximum and minimum values for body mass in <i>D. robustus</i> and <i>P. australis</i> respectively. Area enclosed by dark blue box is expanded in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082668#pone-0082668-g006" target="_blank">Figure 6</a>.</p

Convex hull specimen list and sources of body mass.

<p><i>M</i>_b) was estimated for the convex hull individuals by first generating species-specific least squares regressions of known body mass against a linear metric from the hind limb as reported in the literature. Body mass (</p><p><i>Dromaius novaehollandiae</i> femoral length against body mass derived from carcasses of known body mass from the University of Manchester. Regression equation of </p><p><i>Rhea spp.</i> tibiotarsal length against body mass generated from previously published raw data and one carcass from the University of Manchester. Regression equation of </p

Moa convex hull volumes and body segment volumes.

<p> Trunk values include minimum and maximum volumes defined by shifting the sternum dorsoventrally. Segment values consist of the sum total of left and right elements.</p

Finite element analysis results for torsional loading.

<p>Values represent maximum von Mises stress (Pa) recorded at the midshaft of the bone. For the two moa species, the range of von Mises stresses based on minimum and maximum body mass estimates (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082668#pone-0082668-t004" target="_blank">Table 4</a>) is also presented.</p

The relationship between convex hull volume and literature values for mass in extant ratites.

<p>LR, linear regression; SMA, standardized major axis regression; MA, major axis regression; LRO, linear regression forced through the origin.</p

The distribution of Von Mises stress within moa finite element models.

<p>(<i>a</i>) <i>Dinornis</i> femur loaded in compression (0° from the longest principal axis) experienced a significant degree of bending due to off-axis application of force on the femoral head. (<i>b</i>) <i>Dinornis</i> tibiotarsus experienced lower values of σ_vm under compression, and underwent less bending due to application of forces on the intercondylar eminence. (<i>c</i>) <i>Pachyornis</i> tibiotarsus loaded in bending (90° from the longest principal axis). σ_vm increases towards the fixed end of the beam, with localised areas of stress related to variations in cortical wall thickness. (<i>d</i>) Slice through midshaft of <i>c.</i> Values of σ_vm are highest at the extreme compressional and tensional cortices with a neutral axis of lowest stress values running between. (<i>e</i>) Slice through midshaft of <i>Pachyornis</i> femur loaded in torsion. Stress values increase radially from the endosteal to periosteal surface, with the highest stresses located in regions where cortical wall thickness is at a minimum. For (<i>d</i>) and (<i>e</i>), bone orientation is indicated by coordinate system (a–p, anteroposterior; m–l, mediolateral).</p

Loading regimes for finite element analysis of <i>Dinornis</i> femur

<p>(<i>a</i>) Medial view of femoral head, yellow arrows originate from the nodes to which force is applied. The direction of force is aligned parallel to the long axis of the bone, i.e. loading in compression. (<i>b</i>) Dorsal view of the proximal femoral epiphysis. Orange dot represents constrained control point, and is surrounded by 10 yellow dots representing the nodes to which torsion is applied via the kinematic coupling. (<i>c</i>) Ventral view of the distal femoral condyles. Orange squares represent nodes subject to encastre boundary conditions.</p