Mammary Gland Development as a Sensitive End Point after Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats

BACKGROUND: Atrazine (ATR), a widely used chlorotriazine herbicide, inhibits a number of endocrine-dependent processes, including gonadotrophin surges and mammary gland development in rats. Chlorotriazine herbicides are rapidly metabolized in plants and animals to form a group of metabolites that are detected both in the environment and in exposed animals. The extent to which these metabolites are responsible directly for the observed health effects is not understood. OBJECTIVES: Our goal was to determine if a mixture of ATR metabolites, in proportions found in the environment, might produce developmental effects in Long-Evans rats following exposure late in pregnancy. METHODS: We administered an ATR metabolite mixture (AMM) containing ATR, hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine orally to pregnant Long-Evans rats at 0.09, 0.87, or 8.73 mg/kg body weight (bw)/day, on gestation days 15–19, using 0 and 100 mg ATR/kg bw/day as negative and positive controls, respectively. RESULTS: We observed no significant effect of acute AMM exposure on body weight gain in dams during the dosing period, weight loss in pups on postnatal day (PND)4, or pubertal timing, as is seen with ATR alone. However, as with ATR, we detected delayed mammary gland development, evaluated by whole mount analysis, as early as PND4 in all treatment groups. CONCLUSIONS: Our data suggest that acute exposure to AMM at levels as low as 0.09 mg/kg bw during late pregnancy causes persistent alterations in mammary gland development of female offspring, and that these effects do not appear to be related to bw or associated with pubertal timing

Mechanism for sarcasm detection and classification in Malay social media

The classification of users’ sentiment from social media data can be used to learn public opinion on certain issues. The presence of sarcasm in sentences can hamper the performance of the classification as it tends to “fool” the system. In this paper, we investigate mechanisms for detecting sarcasm in Malay social media data that contain sarcastic contents; more specifically the public comments on economic related posts on Facebook. Two features were investigated; the n-gram and punctuation marks. Features selection in the form of Pearson’s correlation was then applied to reduce the features size. To measure the performances of the selected features, two supervised classification techniques were employed which are k-Nearest Neighbors and non-linear Support Vector Machine. Experiments on sarcasm detection and classification were conducted. Results show that combination of n-gram and punctuation marks produced the best F -measure and Area Under Curve of 0.818 for sarcasm detection. Extended experiment on sarcasm classification recorded F -measure of 0.991 with Area Under Curve of 0.994 for sarcasm positivity while F -measure of 0.902 with Area Under Curve of 0.846 for sarcasm negativity

Individual differences in newborn visual attention associate with temperament and behavioral difficulties in later childhood

Recently it was shown that individual differences in attention style in infants are associated with childhood effortful control, surgency, and hyperactivity-inattention. Here we investigated whether effortful control, surgency and behavioral problems in childhood can be predicted even earlier, from individual differences in newborns’ average duration of gaze to stimuli. Eighty newborns participated in visual preference and habituation studies. Parents completed questionnaires at follow up (mean age = 7.5 years, SD = 1.0 year). Newborns’ average dwell time was negatively associated with childhood surgency (β = -.25, R2 = .04, p = .02) and total behavioral difficulties (β = -.28, R2 = .05, p = .04) but not with effortful control (β = .03, R2 = .001, p = .76). Individual differences in newborn visual attention significantly associated with individual variation in childhood surgency and behavioral problems, showing that some of the factors responsible for this variation are present at birth

XSL: The X-Shooter Spectral Library

We are building a new spectral library with the X-Shooter instrument on ESO's VLT: XSL, the X-Shooter Spectral Library. We present our progress in building XSL, which covers the wavelength range from the near-UV to the near-IR with a resolution of R ~ 10000. At the time of writing we have collected spectra for nearly 240 stars. An important feature of XSL is that we have already collected spectra of more than 100 Asymptotic Giant Branch stars in the Galaxy and the Magellanic Clouds.Comment: 8 pages, 4 figures, to be published in the proceedings of the "GREAT-ESF Stellar Atmospheres in the Gaia Era Workshop", Brussels, Belgium, 23-24 June, 201

Plasmodium knowlesi Genome Sequences from Clinical Isolates Reveal Extensive Genomic Dimorphism.

Plasmodium knowlesi is a newly described zoonosis that causes malaria in the human population that can be severe and fatal. The study of P. knowlesi parasites from human clinical isolates is relatively new and, in order to obtain maximum information from patient sample collections, we explored the possibility of generating P. knowlesi genome sequences from archived clinical isolates. Our patient sample collection consisted of frozen whole blood samples that contained excessive human DNA contamination and, in that form, were not suitable for parasite genome sequencing. We developed a method to reduce the amount of human DNA in the thawed blood samples in preparation for high throughput parasite genome sequencing using Illumina HiSeq and MiSeq sequencing platforms. Seven of fifteen samples processed had sufficiently pure P. knowlesi DNA for whole genome sequencing. The reads were mapped to the P. knowlesi H strain reference genome and an average mapping of 90% was obtained. Genes with low coverage were removed leaving 4623 genes for subsequent analyses. Previously we identified a DNA sequence dimorphism on a small fragment of the P. knowlesi normocyte binding protein xa gene on chromosome 14. We used the genome data to assemble full-length Pknbpxa sequences and discovered that the dimorphism extended along the gene. An in-house algorithm was developed to detect SNP sites co-associating with the dimorphism. More than half of the P. knowlesi genome was dimorphic, involving genes on all chromosomes and suggesting that two distinct types of P. knowlesi infect the human population in Sarawak, Malaysian Borneo. We use P. knowlesi clinical samples to demonstrate that Plasmodium DNA from archived patient samples can produce high quality genome data. We show that analyses, of even small numbers of difficult clinical malaria isolates, can generate comprehensive genomic information that will improve our understanding of malaria parasite diversity and pathobiology

Deliberating stratospheric aerosols for climate geoengineering and the SPICE project

Increasing concerns about the narrowing window for averting dangerous climate change have prompted calls for research into geoengineering, alongside dialogue with the public regarding this as a possible response. We report results of the first public engagement study to explore the ethics and acceptability of stratospheric aerosol technology and a proposed field trial (the Stratospheric Particle Injection for Climate Engineering (SPICE) ‘pipe and balloon’ test bed) of components for an aerosol deployment mechanism. Although almost all of our participants were willing to allow the field trial to proceed, very few were comfortable with using stratospheric aerosols. This Perspective also discusses how these findings were used in a responsible innovation process for the SPICE project initiated by the UK’s research councils

The value of standards for health datasets in artificial intelligence-based applications

Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative)

Eye movements and reading in glaucoma: observations on patients with advanced visual field loss

Purpose To investigate the relationship between reading speed and eye movements in patients with advanced glaucomatous visual field (VF) defects and age-similar visually healthy people. Methods Eighteen patients with advanced bilateral VF defects (mean age: 71, standard deviation [SD]: 7 years) and 39 controls (mean age: 67, SD: 8 years) had reading speed measured using short passages of text on a computer set-up incorporating eye tracking. Scanpaths were plotted and analysed from these experiments to derive measures of ‘perceptual span’ (total number of letters read per number of saccades) and ‘text saturation’ (the distance between the first and last fixation on lines of text). Another eye movement measure, termed ‘saccadic frequency’ (total number of saccades made to read a single word), was derived from a separate lexical decision task, where words were presented in isolation. Results Significant linear association was demonstrated between perceptual span and reading speed in patients (R2=0.42) and controls (R2=0.56). Linear association between saccadic frequency during the LDT and reading speed was also found in patients (R2=0.42), but not in controls (R2=0.02). Patients also exhibited greater average text saturation than controls (P=0.004). Conclusion Some, but not all, patients with advanced VF defects read slower than controls using short text passages. Differences in eye movement behaviour may partly account for this variability in patients. These patients were shown to saturate lines of text more during reading, which may explain previously-reported difficulties with sustained reading

Non-invasive MR imaging techniques for measuring femoral arterial flow in a pediatric and adolescent cohort

This is the final version. Available on open access from Wiley via the DOI in this recordMagnetic Resonance Imaging (MRI) is well-suited for imaging peripheral blood flow due to its non-invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI-based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric-adolescent population using phase contrast MRI, and to present test-retest reliability data for this method. Ten healthy children and adolescents (4 male; mean age 14.8 ± 2.4 years) completed bloodwork and resting and exercise MRI. Baseline images consisted of PC-MRI of the femoral artery at rest and following a 5 × 30 s of in-magnet exercise. To evaluate test-retest reliability, five participants returned for repeat testing. All participants successfully completed exercise testing in the MRI. Baseline flow demonstrated excellent reliability (ICC = 0.93, p = 0.006), and peak exercise and delta rest-peak flow demonstrated good reliability (peak exercise ICC = 0.89, p = 0.002, delta rest-peak ICC = 0.87, p = 0.003) between-visits. All three flow measurements demonstrated excellent reliability when assessed with coefficients of variance (CV's) (rest: CV = 6.2%; peak exercise: CV = 7.3%; delta rest-peak: CV = 7.1%). The mean bias was small for femoral arterial flow. There was no significant mean bias between femoral artery flow visits 1 and 2 at peak exercise. There were no correlations between age or height and any of the flow measurements. There were no significant differences between male and female participants for any of the flow measurements. The current study determined that peripheral arterial blood flow in children and adolescents can be evaluated using non-invasive phase contrast MRI. The MRI-based techniques that were used in the current study for measuring arterial flow in pediatric and adolescent patients demonstrated acceptable test-retest reliability both at rest and immediately post-exercise.Cystic Fibrosis TrustExercise Medicine Fund at the Hospital for Sick Children (Canada

Plasmodium vivax dhfr and dhps mutations in isolates from Madagascar and therapeutic response to sulphadoxine-pyrimethamine

<p>Abstract</p> <p>Background</p> <p>Four of five <it>Plasmodium </it>species infecting humans are present in Madagascar. <it>Plasmodium vivax </it>remains the second most prevalent species, but is understudied. No data is available on its susceptibility to sulphadoxine-pyrimethamine, the drug recommended for intermittent preventive treatment during pregnancy. In this study, the prevalence of <it>P. vivax </it>infection and the polymorphisms in the <it>pvdhfr </it>and <it>pvdhps </it>genes were investigated. The correlation between these polymorphisms and clinical and parasitological responses was also investigated in <it>P. vivax</it>-infected patients.</p> <p>Methods</p> <p><it>Plasmodium vivax </it>clinical isolates were collected in eight sentinel sites from the four major epidemiological areas for malaria across Madagascar in 2006/2007. <it>Pvdhfr </it>and <it>pvdhps </it>genes were sequenced for polymorphism analysis. The therapeutic efficacy of SP in <it>P. vivax </it>infections was assessed in Tsiroanomandidy, in the foothill of the central highlands. An intention-to-treat analysis of treatment outcome was carried out.</p> <p>Results</p> <p>A total of 159 <it>P. vivax </it>samples were sequenced in the <it>pvdhfr/pvdhps </it>genes. Mutant-types in <it>pvdhfr </it>gene were found in 71% of samples, and in <it>pvdhps </it>gene in 16% of samples. Six non-synonymous mutations were identified in <it>pvdhfr</it>, including two novel mutations at codons 21 and 130. For <it>pvdhps</it>, beside the known mutation at codon 383, a new one was found at codon 422. For the two genes, different combinations were ranged from wild-type to quadruple mutant-type. Among the 16 patients enrolled in the sulphadoxine-pyrimethamine clinical trial (28 days of follow-up) and after adjustment by genotyping, 3 (19%, 95% CI: 5%–43%) of them were classified as treatment failure and were <it>pvdhfr </it>58R/117N double mutant carriers with or without the <it>pvdhps </it>383G mutation.</p> <p>Conclusion</p> <p>This study highlights (i) that genotyping in the <it>pvdhfr </it>and <it>pvdhps </it>genes remains a useful tool to monitor the emergence and the spread of <it>P. vivax </it>sulphadoxine-pyrimethamine resistant in order to improve the national antimalarial drug policy, (ii) the issue of using sulphadoxine-pyrimethamine as a monotherapy for intermittent preventive treatment of pregnant women or children.</p