Development of a nonlinear hierarchical model to describe the disposition of deuterium in mother-infant pairs to assess exclusive breastfeeding practice

The World Health Organization recommends exclusive breastfeeding (EBF) for the first 6 months after birth. The deuterium oxide dose-to-the-mother (DTM) technique is used to distinguish EBF based on a cut-off (< 25 g/day) of water intake from sources other than breastmilk. This value is based on a theoretical threshold and has not been verified in field studies. The aim of this study was to estimate the water intake cut-off value that can be used to define EBF practice. One hundred and twenty-one healthy infants, aged 2.5-5.5 months who were deemed to be EBF were recruited. After administration of deuterium to the mothers, saliva was sampled from mother and infant pairs over a 14-day period. Validation of infant feeding practices was conducted via home observation over six non-consecutive days with caregiver recall. A fully Bayesian framework using a gradient-based Markov chain Monte Carlo approach implemented in Stan was used to estimate the cut-off of non-milk water intake of EBF infants. From the original data set, 113 infants were determined to be EBF and provided 1500 paired mother-infant observations. The deuterium saliva concentrations were best described by two linked 1-compartment models (mother and infant), with body weight as a covariate on the mother's volume of distribution and infant's body weight on infant's water clearance rate. The cut-off value was based on the 90th percentile of the posterior distribution of non-milk water intake and was 86.6 g/day. This cut-off value can be used in future field studies in other geographic regions to determine exclusivity of breast feeding practices in order to determine their potential public health needs

Development of a parsimonious design for optimal classification of exclusive breastfeeding

A deuterium oxide dose‐to‐mother (DTM) technique is used to determine if an infant is exclusive breastfeeding (EBF). However, the DTM method is intensive, requiring seven paired mother–infant samples during a 14‐day study period. The purpose of this study was to develop a field‐friendly protocol. Data from 790 mother–infant pairs from nine countries were analyzed using a Markov chain Monte Carlo method with Stan. The data were split into (i) model building (565 pairs) and (ii) design evaluation (225 pairs). EBF classification was based on a previously published cut‐off for nonmilk water intake. Classification based on the full design was the reference (gold standard classification). The receiver operating characteristics of parsimonious designs were used to determine an optimal parsimonious classification method. The best two postdose windows (days 7–9 and 13–14) yielded optimal categorization with similar performance in the design evaluation data. This postdose two‐sample design provided 95% sensitivity and specificity when compared with the full design

Anthelmintic activity of selected ethno-medicinal plant extracts on parasitic stages of Haemonchus contortus

Background: Parasitic roundworms (nematodes) cause substantial morbidity and mortality in livestock animals globally, and considerable productivity losses to farmers. The control of these nematodes has relied largely on the use of a limited number of anthelmintics. However, resistance to many of these these anthelmintics is now widespread, and, therefore, there is a need to find new drugs to ensure sustained and effective treatment and control into the future. Methods: Recently, we developed a screening assay to test natural, plant extracts with known inhibitory effects against the free-living worm Caenorhabditis elegans. Using this assay, we assessed here the effects of the extracts on motility and development of parasitic larval stages of Haemonchus contortus, one of the most important nematodes of small ruminants worldwide. Results: The study showed that two of five extracts from Picria fel-terrae Lour. have a significant inhibitory effect (at concentrations of 3-5 mg/ml) on the motility and development of H. contortus larvae. Although the two extracts originated from the same plant, they displayed different levels of inhibition on motility and development, which might relate to the presence of various active constituents in these extracts, or the same constituents at different concentrations in distinct parts of the plant. Conclusions: These results suggest that extracts from P. fel-terrae Lour. have promising anthelmintic activity and that more broadly, plant extracts are a potential rich source of anthelmintics to combat helminthic diseases. © 2016 Kumarasingha et al

Synchronous in-field application of life-detection techniques in Icelandic Mars analogue sites

Field expeditions that simulate the operations of robotic planetary exploration missions at analogue sites on Earth can help establish best practices and are therefore a positive contribution to the planetary exploration community. There are many sites in Iceland that possess heritage as planetary exploration analogue locations and whose environmental extremes make them suitable for simulating scientific sampling and robotic operations. We conducted a planetary exploration analogue mission at two recent lava fields in Iceland, Fimmvörðuháls (2010) and Eldfell (1973), using a specially developed field laboratory. We tested the utility of in-field site sampling down selection and tiered analysis operational capabilities with three life detection and characterization techniques: fluorescence microscopy (FM), adenine-triphosphate (ATP) bioluminescence assay, and quantitative polymerase chain reaction (qPCR) assay. The study made use of multiple cycles of sample collection at multiple distance scales and field laboratory analysis using the synchronous life-detection techniques to heuristically develop the continuing sampling and analysis strategy during the expedition. Here we report the operational lessons learned and provide brief summaries of scientific data. The full scientific data report will follow separately. We found that rapid in-field analysis to determine subsequent sampling decisions is operationally feasible, and that the chosen life detection and characterization techniques are suitable for a terrestrial life-detection field mission. In-field analysis enables the rapid obtainment of scientific data and thus facilitates the collection of the most scientifically relevant samples within a single field expedition, without the need for sample relocation to external laboratories. The operational lessons learned in this study could be applied to future terrestrial field expeditions employing other analytical techniques and to future robotic planetary exploration missions

Insightful Problem Solving in an Asian Elephant

The “aha” moment or the sudden arrival of the solution to a problem is a common human experience. Spontaneous problem solving without evident trial and error behavior in humans and other animals has been referred to as insight. Surprisingly, elephants, thought to be highly intelligent, have failed to exhibit insightful problem solving in previous cognitive studies. We tested whether three Asian elephants (Elephas maximus) would use sticks or other objects to obtain food items placed out-of-reach and overhead. Without prior trial and error behavior, a 7-year-old male Asian elephant showed spontaneous problem solving by moving a large plastic cube, on which he then stood, to acquire the food. In further testing he showed behavioral flexibility, using this technique to reach other items and retrieving the cube from various locations to use as a tool to acquire food. In the cube's absence, he generalized this tool utilization technique to other objects and, when given smaller objects, stacked them in an attempt to reach the food. The elephant's overall behavior was consistent with the definition of insightful problem solving. Previous failures to demonstrate this ability in elephants may have resulted not from a lack of cognitive ability but from the presentation of tasks requiring trunk-held sticks as potential tools, thereby interfering with the trunk's use as a sensory organ to locate the targeted food

Re-imagining the future:repetition decreases hippocampal involvement in future simulation

Imagining or simulating future events has been shown to activate the anterior right hippocampus (RHC) more than remembering past events does. One fundamental difference between simulation and memory is that imagining future scenarios requires a more extensive constructive process than remembering past experiences does. Indeed, studies in which this constructive element is reduced or eliminated by “pre-imagining” events in a prior session do not report differential RHC activity during simulation. In this fMRI study, we examined the effects of repeatedly simulating an event on neural activity. During scanning, participants imagined 60 future events; each event was simulated three times. Activation in the RHC showed a significant linear decrease across repetitions, as did other neural regions typically associated with simulation. Importantly, such decreases in activation could not be explained by non-specific linear time-dependent effects, with no reductions in activity evident for the control task across similar time intervals. Moreover, the anterior RHC exhibited significant functional connectivity with the whole-brain network during the first, but not second and third simulations of future events. There was also evidence of a linear increase in activity across repetitions in right ventral precuneus, right posterior cingulate and left anterior prefrontal cortex, which may reflect source recognition and retrieval of internally generated contextual details. Overall, our findings demonstrate that repeatedly imagining future events has a decremental effect on activation of the hippocampus and many other regions engaged by the initial construction of the simulation, possibly reflecting the decreasing novelty of simulations across repetitions, and therefore is an important consideration in the design of future studies examining simulation

Candida albicans-produced farnesol stimulates Pseudomonas quinolone signal production in LasR-defective Pseudomonas aeruginosa strains

Candida albicans has been previously shown to stimulate the production of Pseudomonas aeruginosa phenazine toxins in dual-species colony biofilms. Here, we report that P. aeruginosa lasR mutants, which lack the master quorum sensing system regulator, regain the ability to produce quorum-sensing-regulated phenazines when cultured with C. albicans. Farnesol, a signalling molecule produced by C. albicans, was sufficient to stimulate phenazine production in LasR− laboratory strains and clinical isolates. P. aeruginosa ΔlasR mutants are defective in production of the Pseudomonas quinolone signal (PQS) due to their inability to properly induce pqsH, which encodes the enzyme necessary for the last step in PQS biosynthesis. We show that expression of pqsH in a ΔlasR strain was sufficient to restore PQS production, and that farnesol restored pqsH expression in ΔlasR mutants. The farnesol-mediated increase in pqsH required RhlR, a transcriptional regulator downstream of LasR, and farnesol led to higher levels of N-butyryl-homoserine lactone, the small molecule activator of RhlR. Farnesol promotes the production of reactive oxygen species (ROS) in a variety of species. Because the antioxidant N-acetylcysteine suppressed farnesol-induced RhlR activity in LasR− strains, and hydrogen peroxide was sufficient to restore PQS production in las mutants, we propose that ROS are responsible for the activation of downstream portions of this quorum sensing pathway. LasR mutants frequently arise in the lungs of patients chronically infected with P. aeruginosa. The finding that C. albicans, farnesol or ROS stimulate virulence factor production in lasR strains provides new insight into the virulence potential of these strains

Molecular Evolution of Human Immunodeficiency Virus Type 1 upon Transmission between Human Leukocyte Antigen Disparate Donor-Recipient Pairs

BACKGROUND: To address evolution of HIV-1 after transmission, we studied sequence dynamics in and outside predicted epitopes of cytotoxic T lymphocytes (CTL) in subtype B HIV-1 variants that were isolated from 5 therapy-naive horizontal HLA-disparate donor-recipient pairs from the Amsterdam Cohort Studies on HIV-1 infection and AIDS. METHODOLOGY/PRINCIPAL FINDINGS: In the first weeks after transmission, the majority of donor-derived mutations in and outside donor-HLA-restricted epitopes in Gag, Env, and Nef, were preserved in the recipient. Reversion to the HIV-1 subtype B consensus sequence of mutations in- and outside donor-HLA-restricted CTL epitopes, and new mutations away from the consensus B sequence mostly within recipient-HLA-restricted epitopes, contributed equally to the early sequence changes. In the subsequent period (1-2 years) after transmission, still only a low number of both reverting and forward mutations had occurred. During subsequent long-term follow-up, sequence dynamics were dominated by forward mutations, mostly (50-85%) in recipient-HLA-restricted CTL epitopes. At the end of long-term follow-up, on average 43% of the transmitted CTL escape mutations in donor-HLA-restricted epitopes had reverted to the subtype B consensus sequence. CONCLUSIONS/SIGNIFICANCE: The relatively high proportion of long-term preserved mutations after transmission points to a lack of back selection even in the absence of CTL pressure, which may lead to an accumulating loss of critical CTL epitopes. Our data are supportive for a continuous adaptation of HIV-1 to host immune pressures which may have implications for vaccine design