Publications

No abstract is provided for this article.

Background. Hyperlactatemia is a strong predictor of mortality in severe falciparum malaria. Sequestered parasitized erythrocytes and reduced uninfected red blood cell deformability (RCD) compromise microcirculatory flow, leading to anaerobic glycolysis. Methods. In a cohort of patients with falciparum malaria hospitalized in Chittagong, Bangladesh, bulk RCD was measured using a laser diffraction technique, and parasite biomass was estimated from plasma concentrations of Plasmodium falciparum histidine-rich protein 2 (PfHRP2). A multiple linear regression model was constructed to examine their associations with plasma lactate concentrations. Results. A total of 286 patients with falciparum malaria were studied, of whom 224 had severe malaria, and 70 died. Hyperlactatemia (lactate level, ≥4 mmol/L) was present in 111 cases. RCD at shear stresses of 1.7 Pa and 30 Pa was reduced significantly in patients who died, compared with survivors, individuals with uncomplicated malaria, or healthy individuals (P < .05, for all comparisons). Multiple linear regression analysis showed that the plasma PfHRP2 level, parasitemia level, total bilirubin level, and RCD at a shear stress of 1.7 Pa were each independently correlated with plasma lactate concentrations (n = 278; R2 = 0.35). Conclusions. Sequestration of parasitized red blood cells and reduced RCD both contribute to decreased microcirculatory flow in severe disease.

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (NaR). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7–5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82−102) vs 101 (93−110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2−8.1) vs 8.0 (7.6−8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an NaR isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.

Additional file 7. All positions that are variant in RSA0â 3h phenotyped isolates.

ING & INDEXING

The phenotype of parents can have long-lasting effects on the development of offspring as well as on their behaviour, physiology, and morphology as adults. In some cases, these changes may increase offspring fitness but, in others, they can elevate parental fitness at a cost to the fitness of their offspring. Here, we show that in Kalahari meerkats (Suricata suricatta) the circulating glucocorticoid hormones of pregnant females affect the growth and cooperative behaviour of their offspring. We performed a 3-year experiment in wild meerkats to test the hypothesis that stress-mediated maternal effects reduce the potential for offspring to reproduce directly and therefore cause them to exhibit more cooperative behaviour. Daughters (but not sons) born to mothers treated with cortisol during pregnancy were smaller early in life and exhibited significantly more of two types of cooperative behaviour (pup rearing and feeding) once they were adults compared to offspring from control mothers. They also had lower measures of stress hormones as they aged, which could explain the observed increases in cooperative behaviour. Because early growth is a crucial determinant of fitness in female meerkats, our results indicate that stress-mediated maternal effects may reduce the fitness of offspring but may elevate parental fitness as a consequence of increasing the cooperative behaviour of their daughters. Significance Statement Maternal characteristics can have a profound influence on offspring, which are referred to as maternal effects. It is widely assumed that selfish maternal effects, where mothers modify offspring to benefit their own fitness and decrease the fitness of offspring, are rare but this assumption is rarely tested. We show that a stress-mediated maternal effect in meerkats altered the growth, behaviour, and stress physiology of daughters in such a way that benefitted mothers at the expense of their daughters. Daughters from stressed mothers grew more slowly early in life, which should reduce their future reproductive opportunities, but exhibited more cooperative behaviour that should directly benefit their mother. This highlights the important role of sociality in the evolution of maternal effects.

Unknown

Current guidelines advise against primaquine treatment for breastfeeding mothers to avoid the potential for haemolysis in infants with G6PD deficiency. To predict the haemolytic risk, the amount of drug received from the breast milk and the resulting infant drug exposure need to be characterised. Here, we develop a pharmacokinetic model to describe the drug concentrations in breastfeeding women using venous, capillary, and breast milk data. A mother-to-infant model is developed to mimic the infant feeding pattern and used to predict their drug exposures. Primaquine and carboxyprimaquine exposures in infants are <1% of the exposure in mothers. Therefore, even in infants with the most severe G6PD deficiency variants, it is highly unlikely that standard doses of primaquine (0.25-1 mg base/kg once daily given to the mother for 1-14 days) would cause significant haemolysis. After the neonatal period, primaquine should not be restricted for breastfeeding women (Clinical Trials Registration: NCT01780753).

In polygynous species, adult mortality is generally higher in males than in females, and theory predicts that this should result in the evolution of faster rates of senescence in males. Detailed investigations of sex differences in patterns of aging across the many and varied phenotypic characteristics associated with successful reproduction in wild populations of polygynous vertebrates are currently lacking. Here, we use longitudinal data collected from a wild red deer population to compare aging patterns across a range of life-history, behavioral, and morphological traits in both sexes. While males showed more rapid age-related declines in annual breeding success than did females, there was evidence of variation in aging rates among traits within each sex. Traits associated with male breeding performance showed a rapid decline in old age, whereas the morphology and phenology of antlers, a key male secondary sexual characteristic, showed minimal senescence. Female reproductive traits associated with regulation of estrus and gestation showed delayed senescence relative to traits associated with investment in offspring growth during gestation and lactation. Our results suggest that either natural selection or physiological constraint has caused an uncoupling of senescence rates in different physiological systems and, thus, different reproductive traits in this wild vertebrate population.

No abstract is provided for this article.

We investigated the crustal architecture of the Parnaíba basin of NE Brazil by analysing receiver functions along a c. 600 km long transect crossing the central portion of the basin. The transect consisted of nine broadband stations interspaced at c. 70 km distance recording continuously for a period of 15 months, with the goal of improving our understanding of the origin and evolution of this large cratonic basin. Our results show that crustal thickness varies between 39 and 45 km along the transect, gradually thickening towards the depocentre, and that bulk V p / V s ratios vary between 1.70 and 1.78. The crust can be divided into a 2.0–3.5 km thick layer of low-velocity sediments, a 15–20 km thick upper crust (3.5 &lt; V s &lt; 3.6 km s −1 ) and a 18–22 km thick lower crust (3.7 &lt; V s &lt; 3.8 km s −1 ). Near the depocentre, where the crust is thickest, the bottom 10–12 km of the crust are characterized by fast S-velocities (4.0–4.2 km s −1 ). Our findings confirm that stretching of the lithosphere is minimal and compatible with flexural subsidence. However, loading from a thick, high-density layer of mafic intrusive rocks pervading the lower crust – as recently proposed for the basin – is found to be inconsistent with our bulk V p / V s ratios and lower crustal S-velocities. Flexural bending by a deeper load, perhaps related to deep mantle convection, seems more plausible.

The majority of deaths from malaria are in young African children. Parenteral artesunate (ARS) is the first-line treatment for severe falciparum malaria. Since 2015, the World Health Organization has recommended individual doses of 3 mg/kg for children weighing < 20 kg. Recently, the US Food and Drug Administration (FDA) has challenged this recommendation, based on a simulated pediatric population, and argued for a lower dose in younger children (2.4 mg/kg). In this study, we performed population pharmacokinetic (PK) modeling of plasma concentration data from 80 children with severe falciparum malaria in the Democratic Republic of Congo who were given 2.4 mg/kg of ARS intravenously. Bayesian hierarchical modeling and a two-compartment parent drug-metabolite PK model for ARS were used to describe the population PKs of ARS and its main biologically active metabolite dihydroartemisinin. We then generated a virtual population representative of the target population in which the drug is used and simulated the total first-dose exposures. Our study shows that the majority of younger children given the lower 2.4 mg/kg dose of intravenous ARS do not reach the same drug exposures as older children above 20 kg. This finding supports withdrawal of the FDA's recent lower ARS dose recommendation as parenteral ARS is an extremely safe and well-tolerated drug and there is potential for harm from underdosing in this rapidly lethal infection.

Data and code to go with our publication "Diurnal oscillations in gut bacterial load and composition eclipse seasonal and lifetime dynamics in wild meerkats, <em>Suricata suricatta", </em>Nature Communications (2021). <strong>FILE DESCRIPTIONS</strong> <em>****** DATA ******</em> <strong>meerkat_16S_data.tar.gz</strong> # 16S V4 amplicon sequences sequenced on an Illumina MiSeq platform using primer pair 515F and 806R, including all faecal samples, controls, and sand samples. Sequence identifiers and basic metadata are in <strong>sequence_identifiers.csv.</strong> <strong>sequence_identifiers.csv </strong># Simple metadata and identifiers for all sequences/samples (what type of sample/sequencing run, etc), required for QIIME2 processing of the raw fasta.gz files contained in meerkat_16S_data.tar.gz. It contains a column for whether the sample was included in the final analysis. Does not include sample biological metadata as generating this data requires access to Kalahari Meerkat Project database. Biological metadata for samples included in the final analysis are instead provided in <strong>processed_data_phyloseq.RDS </strong>and can be accessed via <em>phyloseq::sample_data(processed_data_phyloseq)</em>. <strong>processed_data_phyloseq.RDS</strong> # Phyloseq object containing the processed data used in the presented analysis. Contains data for 1109 samples, and includes the ASV table, the taxonomic classification, the phylogenetic tree, and the sample metadata used in the analysis. <strong>technical_replicate_data_phyloseq.RDS</strong> # Phyloseq object containing data from the 16 technical replicates. <strong>pilot_study_data_phyloseq.RDS</strong> # Phyloseq object containing data from the pilot study on captive meerkats. <em>****** CODE ******</em> <strong>CODE1_QIIME_script.R</strong> # QIIME2 script to generate ASV table, taxonomy, and phylo tree from <strong>meerkat_16S_data.tar.gz. </strong>Requires a reference taxonomy (SILVA) and a reference phylogeny (SEPP) for taxonomic and phylogenetic placements. <strong>CODE2_processing_QIIME_output.Rmd</strong> # R markdown script that processes the QIIME2 output generated by <strong>CODE1_QIIME_script.R</strong>. Does not generate meerkat metadata as this requires access to the Kalahari Meerkat Project database. This metadata is provided in <strong>processed_data_phyloseq.RDS.</strong> <strong>CODE3_data_analysis_script.Rmd </strong># R markdown script that generates data and figures presented in paper, using data from <strong>processed_data_phyloseq.RDS, technical_replicate_data_phyloseq.RDS, </strong>and<strong> pilot_study_data_phyloseq.RDS.</strong> <em>****** R MARKDOWN REPORTS ******</em> The following reports are html files that show the code output for the two RMD files above. <strong>RMARKDOWN_data_processing.html </strong># R markdown report for<strong> CODE2_processing_QIIME_output.Rmd</strong> <strong>RMARKDOWN_data_analysis.html </strong># R markdown report for <strong>CODE3_data_analysis_script.Rmd</strong> ***************************** For general queries, unexpected errors and/or inconsistencies, please contact riselya@gmail.com.