Comparing the retinal structures and functions in two species of gulls (Larus delawarensis and Larus modestus) with significant nocturnal behaviours

AbstractRing-billed gulls (Larus delawarensis) and gray gulls (Larus modestus) are two species active both by day and night. We have investigated the retinal adaptations that allow the diurnal and nocturnal behaviours of these two species. Electroretinograms and histological analyses show that both species have a duplex retina in which cones outnumber rods, but the number of rods appears sufficient to provide vision at night. Their retinas respond over the same scotopic dynamic range of 3.4logcdm−2, which encompasses all of the light levels occurring at night in their photic environment. The amplitudes of the scotopic saturated a- and b-wave responses as well as the photopic saturated b-wave response and the photopic sensitivity parameter S are however higher in ring-billed gulls than in gray gulls. Moreover, the process of dark adaptation is about 30min faster in gray gulls than in ring-billed gulls. Our results suggest that both species have acquired in the course of their evolution functional adaptations that can be related to their specific photic environment

Data relating to early child development in the Avon Longitudinal Study of Parents and Children (ALSPAC), their relationship with prenatal blood mercury and stratification by fish consumption.

As part of the Avon Longitudinal Study of Parents and Children (ALSPAC), measures of early child development were collected using both hands-on expert assessment (on a random 10% sub-sample) by trained psychologists at 18 months using the Griffiths Mental Development Scales (Extended 0–8 years) and from detailed questionnaires completed by the study mothers on the whole cohort using assessments based on the Denver Developmental Screening Test. The development determined by the psychologists on the 10% subsample showed a correlation of 0.49 (R. Wilson, 2003) [9] with the developmental level estimated from the maternal report. Maternal reports were used to determine the associations between prenatal blood mercury levels and scores of social achievement, fine motor skills, gross motor skills and communication at various preschool ages. (For results, please see doi:10.1016/j.neuro.2016.02.006 [1].

Genomics of antibiotic-resistance prediction in Pseudomonas aeruginosa

Antibiotic resistance is a worldwide health issue spreading quickly among human and animal pathogens, as well as environmental bacteria. Misuse of antibiotics has an impact on the selection of resistant bacteria, thus contributing to an increase in the occurrence of resistant genotypes that emerge via spontaneous mutation or are acquired by horizontal gene transfer. There is a specific and urgent need not only to detect antimicrobial resistance but also to predict antibiotic resistance in silico. We now have the capability to sequence hundreds of bacterial genomes per week, including assembly and annotation. Novel and forthcoming bioinformatics tools can predict the resistome and the mobilome with a level of sophistication not previously possible. Coupled with bacterial strain collections and databases containing strain metadata, prediction of antibiotic resistance and the potential for virulence are moving rapidly toward a novel approach in molecular epidemiology. Here, we present a model system in antibiotic-resistance prediction, along with its promises and limitations. As it is commonly multidrug resistant, Pseudomonas aeruginosa causes infections that are often difficult to eradicate. We review novel approaches for genotype prediction of antibiotic resistance. We discuss the generation of microbial sequence data for real-time patient management and the prediction of antimicrobial resistance

Associations between prenatal mercury exposure and early child development in the ALSPAC study

AbstractIntroductionThere is evidence that high levels of mercury exposure to the pregnant woman can result in damage to the brain of the developing fetus. However there is uncertainty as to whether lower levels of the metal have adverse effects on the development of the infant and whether components of fish consumption and/or the selenium status of the woman is protective.MethodsIn this study we analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=2875–3264) to determine whether levels of total blood mercury of pregnant women collected in the first half of pregnancy are associated with the development of the offspring at ages 6, 18, 30 and 42 months. The developmental measures used maternal self-reported scales for individual types of development (fine and gross motor, social and communication skills) and total scores. Multiple and logistic regression analyses treated the outcomes both as continuous and as suboptimal (the lowest 15th centile). The statistical analyses first examined the association of prenatal mercury exposure with these developmental endpoints and then adjusted each for a number of social and maternal lifestyle factors; finally this model was adjusted for the blood selenium level.ResultsTotal maternal prenatal blood mercury and selenium ranged from 0.17 to 12.76 and 17.0 to 324μg/L respectively. We found no evidence to suggest that prenatal levels of maternal blood mercury were associated with adverse development of the child, even when the mother had consumed no fish during pregnancy. In general, the higher the mercury level the more advanced the development of the child within the range of exposure studied. For example, the fully adjusted effect sizes for total development at 6 and 42 months were +0.51 [95%CI +0.05, +1.00] and +0.43 [95%CI +0.08, +0.78] points per SD of mercury. For the risk of suboptimal development the ORs at these ages were 0.90 [95%CI 0.80, 1.02] and 0.88 [95%CI 0.77, 1.02]. In regard to the associations between blood mercury and child development there were no differences between the mothers who ate fish and those who did not, thus implying that the benefits were not solely due to the beneficial nutrients in fish.ConclusionsWe found no evidence of adverse associations between maternal prenatal blood mercury and child development between 6 and 42 months of age. The significant associations that were present were all in the beneficial direction

Implementation and validation of time-of-flight PET image reconstruction module for listmode and sinogram projection data in the STIR library

In this paper, we describe the implementation of support for time-of-flight (TOF) positron emission tomography (PET) for both listmode and sinogram data in the open source software for tomographic image reconstruction (STIR). We provide validation and performance characterization using simulated data from the open source GATE Monte Carlo toolbox, with TOF configurations spanning from 81.2 to 209.6 ps. The coincidence detector resolution was corrected for the timing resolution deterioration due to the contribution of the crystal length. Comparison between the reconstruction of listmode and sinogram data demonstrated good agreement in both TOF and non-TOF cases in terms of relative absolute error. To reduce the reconstruction time, we assessed the truncation of the TOF kernel along lines-of-response (LOR). Rejection of LOR elements beyond four times the TOF standard deviation provides significant acceleration of without compromising the image quality. Further narrowing of the kernel can provide extra time reduction but with the gradual introduction of error in the reconstructed images. As expected, TOF reconstruction performs better than non-TOF in terms of both contrast-recovery-coefficient (CRC) and signal-to-noise ratio (SNR). CRC achieves convergence faster with TOF, at lower noise levels. SNR with TOF was superior for early iterations, but with quick deterioration. Higher timing resolution further improved reconstruction performance, while TOF bin mashing was shown to have only a small impact on reconstructed images

TLR4 genetic variation is associated with inflammatory responses in Gram-positive sepsis.

OBJECTIVES: To identify important pathogen recognition receptor (PRR) pathways regulating innate immune responses and outcome in Staphylococcus aureus sepsis. METHODS: We analysed whether candidate PRR pathway genetic variants were associated with killed S. aureus-induced cytokine responses ex vivo and performed follow-up in vitro studies. We tested the association of our top-ranked variant with cytokine responses and clinical outcomes in a prospective multicentre cohort of patients with staphylococcal sepsis. RESULTS: An intronic TLR4 polymorphism and expression quantitative trait locus, rs1927907, was highly associated with cytokine release induced by stimulation of blood from healthy Thai subjects with S. aureus ex vivo. S. aureus did not induce TLR4-dependent NF-κB activation in transfected HEK293 cells. In monocytes, tumor necrosis factor (TNF)-α release induced by S. aureus was not blunted by a TLR4/MD-2 neutralizing antibody, but in a monocyte cell line, TNF-α was reduced by knockdown of TLR4. In Thai patients with staphylococcal sepsis, rs1927907 was associated with higher interleukin (IL)-6 and IL-8 levels as well as with respiratory failure. S. aureus-induced responses in blood were most highly correlated with responses to Gram-negative stimulants whole blood. CONCLUSIONS: A genetic variant in TLR4 is associated with cytokine responses to S. aureus ex vivo and plasma cytokine levels and respiratory failure in staphylococcal sepsis. While S. aureus does not express lipopolysaccharide or activate TLR4 directly, the innate immune response to S. aureus does appear to be modulated by TLR4 and shares significant commonality with that induced by Gram-negative pathogens and lipopolysaccharide

Implementation of Image Reconstruction for GE SIGNA PET/MR PET Data in the STIR Library

Software for Tomographic Image Reconstruction (STIR: http://stir.sf.net) is an open source C++ library available for reconstruction of emission tomography data. This work aims at the incorporation of the GE SIGNA PET/MR scanner in STIR and enables PET image reconstruction with data corrections. The data extracted from the scanner after an acquisition includes a list of raw data files (emission, normalisation, geometric and well counter calibration (wcc) factors), magnetic resonance attenuation correction (MRAC) images and the scanner-based reconstructions. The listmode (LM) file stores a list of 'prompt' events and the singles per crystal per second. MRAC images from the scanner are used for attenuation correction. The modifications to STIR that allow accurate histogramming of this LM data in the same sinogram organisation as the scanner are also described. This allows reconstruction of acquisition data with all data corrections using STIR, and independent of any software supplied by the manufacturer. The implementations were validated by comparing the histogrammed data, data corrections and final reconstruction using the ordered subset expectation maximisation (OSEM) algorithm with the equivalents from the GE-toolbox, supplied by the manufacturer for the scanner. There is no difference in the histogrammed counts whereas an overall relative difference of 6.7 × 10 -8 % and from 0.01% to 0.86% is seen in the normalisation and randoms correction sinograms respectively. The STIR reconstructed images have similar resolution and quantification but have some residual differences due to wcc factors, decay and deadtime corrections, as well as the offset between PET and MR gantries that will be addressed in future work. This work will enable the use of all current and future STIR algorithms, including penalized image reconstruction, motion correction and direct parametric image estimation, on data from GE SIGNA PET/MR scanners

Reducing work pressure and IT problems and facilitating IT integration and audit & feedback help adherence to perioperative safety guidelines: a survey among 95 perioperative professionals

Background: To improve perioperative patient safety, guidelines for the preoperative, peroperative, andpostoperative phase were introduced in the Netherlands between 2010 and 2013. To help the implementation ofthese guidelines, we aimed to get a better understanding of the barriers and drivers of perioperative guidelineadherence and to explore what can be learned for future implementation projects in complex organizations.Methods: We developed a questionnaire survey based on the theoretical framework of Van Sluisveld et al. forclassifying barriers and facilitators. The questionnaire contained 57 statements derived from (a) an instrument formeasuring determinants of innovations by the Dutch Organization for Applied Scientific Research, (b) interviewswith quality and safety policy officers and perioperative professionals, and (c) a publication of Cabana et al. Thetarget group consisted of 232 perioperative professionals in nine hospitals. In addition to rating the statements on afive-point Likert scale (which were classified into the seven categories of the framework: factors relating to theintervention, society, implementation, organization, professional, patients, and social factors), respondents wereinvited to rank their three most important barriers in a separate, extra open-ended question.Results: Ninety-five professionals (41%) completed the questionnaire. Fifteen statements (26%) were considered tobe barriers, relating to social factors (N = 5), the organization (N = 4), the professional (N = 4), the patient (N = 1),and the intervention (N = 1). An integrated information system was considered an important facilitator (70.4%) aswell as audit and feedback (41.8%). The Barriers Top-3 question resulted in 75 different barriers in nearly allcategories. The most frequently reported barriers were as follows: time pressure (16% of the total number ofbarriers), emergency patients (8%), inefficient IT structure (4%), and workload (3%).Conclusions: We identified a wide range of barriers that are believed to hinder the use of the perioperative safetyguidelines, while an integrated information system and local data collection and feedback will also be necessary toengage perioperative teams. These barriers need to be locally prioritized and addressed by tailored implementationstrategies. These results may also be of relevance for guideline implementation in general in complex organizations.Trial registration: Dutch Trial Registry: NTR3568.Keywords: Guideline adherence, Implementation, Implementation barriers, Implementation facilitators, Patientsafety, Perioperative car

A megaplasmid family driving dissemination of multidrug resistance in Pseudomonas.

Multidrug resistance (MDR) represents a global threat to health. Here, we used whole genome sequencing to characterise Pseudomonas aeruginosa MDR clinical isolates from a hospital in Thailand. Using long-read sequence data we obtained complete sequences of two closely related megaplasmids (>420 kb) carrying large arrays of antibiotic resistance genes located in discrete, complex and dynamic resistance regions, and revealing evidence of extensive duplication and recombination events. A comprehensive pangenomic and phylogenomic analysis indicates that: 1) these large plasmids comprise an emerging family present in different members of the Pseudomonas genus, and associated with multiple sources (geographical, clinical or environmental); 2) the megaplasmids encode diverse niche-adaptive accessory traits, including multidrug resistance; 3) the accessory genome of the megaplasmid family is highly flexible and diverse. The history of the megaplasmid family, inferred from our analysis of the available database, suggests that members carrying multiple resistance genes date back to at least the 1970s