Distribution of survival times of deliberate Plasmodium falciparum infections in tertiary syphilis patients

Survival time data of Plasmodium falciparum infections from deliberate infection of human subjects with P. falciparum between 1940 and 1963 as a treatment for neurosyphilis in the USA (Georgia) have been used to test the fits of five commonly used parametric distributions for survival times using quantile-quantile plots. Our results suggest that the best fit is obtained from the Gompertz or Weibull distributions. This result has important implications for mathematical modelling of malaria, which has for the past century exclusively assumed that the duration of malaria infections has an exponential distribution. It is desirable to know the correct distribution because its shape profoundly influences the length of monitoring needed in an intervention programme for eliminating or reducing malari

Algorithms for efficient symbolic detection of faults in context-aware applications.

Context-aware and adaptive applications running on mobile devices pose new challenges for the verification community. Current verification techniques are tailored for different domains (mostly hardware) and the kind of faults that are typical of applications running on mobile devices are difficult (or impossible) to encode using the patterns of ldquotraditionalrdquo verification domains. In this paper we present how techniques similar to the ones used in symbolic model checking can be applied to the verification of context-aware and adaptive applications. More in detail, we show how a model of a context-aware application can be encoded by means of ordered binary decision diagrams and we introduce symbolic algorithms for the verification of a number of properties

Ecology, conservation, and phylogenetic position of the Madagascar Jacana Actophilornis albinucha

The Madagascar Jacana Actophilornis albinucha (Jacanidae) is an endemic shorebird found in the threatened wetlands of western Madagascar. This species is presumed to exhibit classical polyandry; however, few data are available to support that assumption. More generally, a lack of basic understanding of this species hinders conservation efforts. We conducted the most extensive study of the Madagascar Jacana to date, and report on its: 1) distribution, population size and density; 2) degree of sexual size dimorphism; and 3) phylogenetic position. The surveys were conducted at 54 lakes, between January and October in 2016. Madagascar Jacana were found at 22 lakes, and within these were distributed at a mean density of 3.5 ± 0.74 [SE] individuals per hectare of surveyed habitat. We estimate the global population size to be between 975 and 2 064 individuals, and habitat destruction appears to be the main threat to the species. Females were significantly larger than males, consistent with reports for other Jacanidae species. Using a mitochondrial DNA fragment, we expanded the Jacanidae genetic phylogeny, and confirmed that Madagascar Jacana is the sister species to the African Jacana Actophilornis africanus. Further studies are urgently needed to thoroughly re-assess the threat status and population trend of the Madagascar Jacana

Endemicity response timelines for Plasmodium falciparum elimination

Background: The scaling up of malaria control and renewed calls for malaria eradication have raised interest in defining timelines for changes in malaria endemicity. Methods: The epidemiological theory for the decline in the Plasmodium falciparum parasite rate (PfPR, the prevalence of infection) following intervention was critically reviewed and where necessary extended to consider superinfection, heterogenous biting, and aging infections. Timelines for malaria control and elimination under different levels of intervention were then established using a wide range of candidate mathematical models. Analysis focused on the timelines from baseline to 1% and from 1% through the final stages of elimination. Results: The Ross-Macdonald model, which ignores superinfection, was used for planning during the Global Malaria Eradication Programme (GMEP). In models that consider superinfection, PfPR takes two to three years longer to reach 1% starting from a hyperendemic baseline, consistent with one of the few large-scale malaria control trials conducted in an African population with hyperendemic malaria. The time to elimination depends fundamentally upon the extent to which malaria transmission is interrupted and the size of the human population modelled. When the PfPR drops below 1%, almost all models predict similar and proportional declines in PfPR in consecutive years from 1% through to elimination and that the waiting time to reduce PfPR from 10% to 1% and from 1% to 0.1% are approximately equal, but the decay rate can increase over time if infections senesce. Conclusion: The theory described herein provides simple "rules of thumb" and likely time horizons for the impact of interventions for control and elimination. Starting from a hyperendemic baseline, the GMEP planning timelines, which were based on the Ross-Macdonald model with completely interrupted transmission, were inappropriate for setting endemicity timelines and they represent the most optimistic scenario for places with lower endemicity. Basic timelines from PfPR of 1% through elimination depend on population size and low-level transmission. These models provide a theoretical basis that can be further tailored to specific control and elimination scenarios

Energy Performance of Advanced Reboiled and Flash Stripper Configurations for CO2 Capture Using Monoethanolamine

CO2 capture by absorption using amine solvents has the potential to significantly reduce the CO2 emissions from fossil-fuel power plants. One of the major costs of this technology is the energy required for solvent regeneration. Complex process configurations claim to have promising potential to reduce the energy required for solvent regeneration. In this work, the effect of flow-sheet complexity is explored by studying two advanced stripping flow sheets: an advanced flash stripper and an advanced reboiled stripper. Both advanced configurations recover the stripping steam heat by means of a heat integration comprised of cold- and warm-rich solvent bypasses. The advanced configurations are simulated and optimized in Aspen Plus V.8.4 using 7 m monoethanolamine (MEA) with lean loading from 0.15 to 0.38 (mol CO2/mol MEA). The rich loading associated with each lean loading is determined by simulating the absorber providing 90% capture from flue gas with 4 mol % CO2, typical of a natural gas-fired turbine. The results are compared to a simple stripper in terms of total equivalent work. Both the advanced reboiled stripper and the advanced flash stripper require 12% less equivalent work than a simple stripper. The associated cold-rich and warm-rich bypasses for the optimum cases are, respectively, 20% and 50% for the advanced reboiled stripper and 15% and 35% for the advanced flash stripper

Targeted suicide gene transfections reveal promising results in nu/nu mice with aggressive neuroblastoma

Neuroblastoma represents the third most common malign neoplasm occurring in children and the most common in newborn. Although mortality in childhood cancer declined in the last decade, high-risk patients have poor prospects, due to the aggressiveness of the cancer. In the recent past, we underlined the potential of sapofectosid as novel and efficient transfection enhancer, demonstrating non-toxic gene delivery, but its value in tumor therapies has yet to be elucidated. A suicide gene, coding for saporin, a ribosome-inactivating protein type I, was incorporated into targeted, peptide-based nanoplexes. The nanoplexes were characterized for their size, zeta potential and appearance by electron microscopy. Gene delivery was observed via confocal imaging. In vitro transfections were conducted to monitor the real-time cell viability. After initial tolerability studies, NMRI nu/nu-mice bearing tumors from Neuro-2A-Luc-cells (murine neuroblastoma cells, transduced with a luciferase gene), were treated with targeted nanoplexes (30 μg saporin-DNA i.v./treatment) and sapofectosid (30 μg s.c. treatment). The treatment was compared to a vehicle (PBS) control and treatment without sapofectosid in terms of body weight, tumor growth and integrated density of tumor luminescence. The study revealed an anti-tumoral effect of the sapofectosid mediated gene therapy in the Neuro-2A-tumor model. The treatments were well tolerated by the animals indicating the applicability of this approach. With these results, we were able to proof the efficacy of a therapy, consisting of targeted suicide gene nanoplexes and sapofectosid, a novel and potent transfection enhancer. This study points out the enormous value for future targeted cancer and gene therapies

Detectability of Plasmodium falciparum clones

BACKGROUND: In areas of high transmission people often harbour multiple clones of Plasmodium falciparum, but even PCR-based diagnostic methods can only detect a fraction (the detectability, q) of all clones present in a host. Accurate measurements of detectability are desirable since it affects estimates of multiplicity of infection, prevalence, and frequency of breakthrough infections in clinical drug trials. Detectability can be estimated by typing repeated samples from the same host but it has been unclear what should be the time interval between the samples and how the data should be analysed. METHODS: A longitudinal molecular study was conducted in the Kassena-Nankana district in northern Ghana. From each of the 80 participants, four finger prick samples were collected over a period of 8 days, and tested for presence of different Merozoite Surface Protein (msp) 2 genotypes. Implications for estimating q were derived from these data by comparing the fit of statistical models of serial dependence and over-dispersion. RESULTS: The distribution of the frequencies of detection for msp2 genotypes was close to binomial if the time span between consecutive blood samples was at least 7 days. For shorter intervals the probabilities of detection were positively correlated, i.e. the shorter the interval between two blood collections, the more likely the diagnostic results matched for a particular genotype. Estimates of q were rather insensitive to the statistical model fitted. CONCLUSIONS: A simple algorithm based on analysing blood samples collected 7 days apart is justified for generating robust estimates of detectability. The finding of positive correlation of detection probabilities for short time intervals argues against imperfect detection being directly linked to the 48-hour periodicity of P. falciparum. The results suggest that the detectability of a given parasite clone changes over time, at an unknown rate, but fast enough to regard blood samples taken one week apart as statistically independent

Long-term survivors of early breast cancer treated with chemotherapy are characterized by a pro-inflammatory biomarker profile compared to matched controls

Background: Chemo- and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment. The pathophysiology behind these late cardiac effects is poorly understood. Therefore, we studied a large panel of biomarkers from different pathophysiological domains in long-term BC survivors, and compared these to matched controls. Methods and results: In total 91 biomarkers were measured in 688 subjects: 342 BC survivors stratified either to treatment with chemotherapy ± radiotherapy (n = 170) or radiotherapy alone (n = 172) and matched controls. Mean age was 59 ± 9 years and 65 ± 8 years for women treated with chemotherapy ± radiotherapy and radiotherapy alone, respectively, with a mean time since treatment of 11 ± 5.5 years. No biomarkers were differentially expressed in survivors treated with radiotherapy alone vs. controls (P for all >0.1). In sharp contrast, a total of 19 biomarkers were elevated, relative to controls, in BC survivors treated with chemotherapy ± radiotherapy after correction for multiple comparisons (P <0.05 for all). Network analysis revealed upregulation of pathways relating to collagen degradation and activation of matrix metalloproteinases. Furthermore, several inflammatory biomarkers including growth differentiation factor 15, monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 16, tumour necrosis factor super family member 13b and proprotein convertase subtilisin/kexin type 9, elevated in survivors treated with chemotherapy, showed an independent association with lower left ventricular ejection fraction. Conclusion: Breast cancer survivors treated with chemotherapy ± radiotherapy show a distinct biomarker profile associated with mild cardiac dysfunction even 10 years after treatment. These results suggest that an ongoing pro-inflammatory state and activation of matrix metalloproteinases following initial treatment with chemotherapy might play a role in the observed cardiac dysfunction in late BC survivors

How Much Remains Undetected? Probability of Molecular Detection of Human Plasmodia in the Field

BACKGROUND: In malaria endemic areas, most people are simultaneously infected with different parasite clones. Detection of individual clones is hampered when their densities fluctuate around the detection limit and, in case of P. falciparum, by sequestration during part of their life cycle. This has important implications for measures of levels of infection or for the outcome of clinical trials. This study aimed at measuring the detectability of individual P. falciparum and P. vivax parasite clones in consecutive samples of the same patient and at investigating the impact of sampling strategies on basic epidemiological measures such as multiplicity of infection (MOI). METHODS: Samples were obtained in a repeated cross-sectional field survey in 1 to 4.5 years old children from Papua New Guinea, who were followed up in 2-monthly intervals over 16 months. At each follow-up visit, two consecutive blood samples were collected from each child at intervals of 24 hours. Samples were genotyped for the polymorphic markers msp2 for P. falciparum and msp1F3 and MS16 for P. vivax. Observed prevalence and mean MOI estimated from single samples per host were compared to combined data from sampling twice within 24 h. FINDINGS AND CONCLUSION: Estimated detectability was high in our data set (0.79 [95% CI 0.76-0.82] for P. falciparum and, depending on the marker, 0.61 [0.58-0.63] or 0.73 [0.71-0.75] for P. vivax). When genotyping data from sequential samples, collected 24 hours apart, were combined, the increase in measured prevalence was moderate, 6 to 9% of all infections were missed on a single day. The effect on observed MOI was more pronounced, 18 to 31% of all individual clones were not detected in a single bleed. Repeated sampling revealed little difference between detectability of P. falciparum and P. vivax