Placental transporter localization and expression in the Human : the importance of species, sex, and gestational age differences

Grant Support: This work was supported by the Medical Research Council, UK (MR/L010011/1 to PAF, PJOS) and a Glasgow Children's Hospital Charity Research Fund and University of Aberdeen, UK, Elphinstone Scholarship to NW.Peer reviewedPublisher PD

Maternal smoking and high BMI disrupt thyroid gland development

This study was supported by grants from the Medical Research Council (MR/L010011/1) (to PAF & PJOS), the Natural Science and Engineering Research Council of Canada (NSERC) for TK and SHK, and NHS Endowment Grant (to PF).Peer reviewedPublisher PD

Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta

This research was supported by the Medical Research Council (UK) grant MR/L010011/1 and the Intramural Research Program at the National Institute on Drug Abuse of the National Institutes of Health. Paired fetal liver and placenta samples were graciously provided by the Joint Medical Research Council/Wellcome Trust (grant number 099175/Z/12/Z) Human Developmental Biology Resource (www.hdbr.org). The online version of this article (doi:10.1007/s11419-017-0389-2) contains supplementary material, which is available to authorized users.Peer reviewedPostprin

Alternative (backdoor) androgen production and masculinization in the human fetus

Funding: The study was supported by the following grants: Chief Scientist Office (Scottish Executive, CZG/4/742) (PAF and PJOS) (http://www.cso.scot.nhs.uk/funding-2/); NHS Grampian Endowments 08/02 (PAF and PJOS) and 15/1/010 (PAF, PF, US, and PJOS) (https://www.nhsgcharities.com/); the Glasgow Children’s Hospital Research Charity Research Fund, YRSS/PHD/2016/05 (NW, MB, PJOS, and PAF) (http://www.glasgowchildrenshospitalcharity.org/research/glasgow-childrens-hospital-charity-research-fund); the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement number 212885 (PAF) (https://ec.europa.eu/research/fp7/index_en.cfm); Medical Research Council Grants MR/L010011/1 (PAF and PJOS) and MR/K501335/1 (MB, PAF, and PJOS) (https://mrc.ukri.org/); and the Kronprinsessan Lovisas Foundation, “Stiftelsen Gunvor och Josef Anérs,” the “Stiftelsen Jane och Dan Olssons,” and the “Stiftelsen Tornspiran” (KS and OS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Human anogenital distance: an update on fetal smoke-exposure and integration of the perinatal literature on sex differences

study question: Do sex and maternal smoking effects on human fetal anogenital distance (AGD) persist in a larger study and how do these data integrate with the wider literature on perinatal human AGD, especially with respect to sex differences? summary answer: Second trimester sex differences in AGD are broadly consistent with neonatal and infant measures of AGD and maternal cigarette smoking is associated with a temporary increase in male AGD in the absence of changes in circulating testosterone. what is known already: AGD is a biomarker of fetal androgen exposure, a reduced AGD in males being associated with cryptorchidism, hypospadias and reduced penile length. Normative fetal AGD data remain partial and windows of sensitivity of human fetal AGD to disruption are not known. study design, size, duration: The effects of fetal sex and maternal cigarette smoking on the second trimester (11 –21 weeks of gestation) human fetal AGD were studied, along with measurement of testosterone and testicular transcripts associated with apoptosis and proliferation. participants/materials, setting methods: AGD, measured from the centre of the anus to the posterior/caudal root of penis/clitoris (AGDapp) was determined in 56 female and 70 male morphologically normal fetuses. These data were integrated with current literature on perinatal AGD in humans. main results and the role of chance: At 11 – 13 weeks of gestation male fetal AGDapp was 61% (P , 0.001) longer than in females, increasing to 70% at 17 – 21 weeks. This sexual dimorphism was independent of growth characteristics (fetal weight, length, gonad weight). We confirmed that at 14 – 16 weeks of gestation male fetal AGDapp was increased 28% (P , 0.05) by in utero cigarette smoke exposure. Testosterone levels were not affected by smoking. To develop normative data, our findings have been integrated with available data from in vivo ultrasound scans and neonatal studies. Inter-study variations in male/female AGD differences lead to the conclusion that normalization and standardization approaches should be developed to enable confidence in comparing data from different perinatal AGD studies. limitations, reasons for caution: Sex differences, and a smoking-dependent increase in male fetal AGD at 14 – 16 weeks, identified in a preliminary study, were confirmed with a larger number of fetuses. However, human fetal AGD should, be re-assessed once much larger numbers of fetuses have been studied and this should be integrated with more detailed analysis of maternal lifestyle. Direct study of human fetal genital tissues is required for further mechanistic insights

Ribosome formation from subunits studied by stopped-flow and Rayleigh light scattering

Light scattering and standard stopped-flow techniques were used to monitor rapid association of ribosomal subunits during initiation of eubacterial protein synthesis. The effects of the initiation factors IF1, IF2, IF3 and buffer conditions on subunit association were studied along with the role of GTP in this process. The part of light scattering theory that is essential for kinetic measurements is high-lighted in the main text and a more general treatment of Rayleigh scattering from macromolecules is given in an appendix

Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming

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Toward a standard for the evaluation of PET-Auto-Segmentation methods following the recommendations of AAPM task group No. 211: Requirements and implementation

Purpose: The aim of this paper is to define the requirements and describe the design and implementation of a standard benchmark tool for evaluation and validation of PET-auto-segmentation (PET-AS) algorithms. This work follows the recommendations of Task Group 211 (TG211) appointed by the American Association of Physicists in Medicine (AAPM).Methods: The recommendations published in the AAPM TG211 report were used to derive a set of required features and to guide the design and structure of a benchmarking software tool. These items included the selection of appropriate representative data and reference contours obtained from established approaches and the description of available metrics. The benchmark was designed in a way that it could be extendable by inclusion of bespoke segmentation methods, while maintaining its main purpose of being a standard testing platform for newly developed PET-AS methods. An example of implementation of the proposed framework, named PETASset, was built. In this work, a selection of PET-AS methods representing common approaches to PET image segmentation was evaluated within PETASset for the purpose of testing and demonstrating the capabilities of the software as a benchmark platform.Results: A selection of clinical, physical, and simulated phantom data, including "best estimates" reference contours from macroscopic specimens, simulation template, and CT scans was built into the PETASset application database. Specific metrics such as Dice Similarity Coefficient (DSC), Positive Predictive Value (PPV), and Sensitivity (S), were included to allow the user to compare the results of any given PET-AS algorithm to the reference contours. In addition, a tool to generate structured reports on the evaluation of the performance of PET-AS algorithms against the reference contours was built. The variation of the metric agreement values with the reference contours across the PET-AS methods evaluated for demonstration were between 0.51 and 0.83, 0.44 and 0.86, and 0.61 and 1.00 for DSC, PPV, and the S metric, respectively. Examples of agreement limits were provided to show how the software could be used to evaluate a new algorithm against the existing state-of-the art.Conclusions: PETASset provides a platform that allows standardizing the evaluation and comparison of different PET-AS methods on a wide range of PET datasets. The developed platform will be available to users willing to evaluate their PET-AS methods and contribute with more evaluation datasets. </p

Controlling R&D Projects: Framing a Process

The purpose of the following paper is to increase the control reliability for R&amp;D projects developed in Tecnimont S.p.A.. The control process should provide accurate results to allow the realistic description of project progress, and it is more complex when dealing with R&amp;D projects: the uncertainty for some activities complicates the process of assigning variances and, consequently, the schedule becomes less robust. The proposal of a control process came after a careful study of previous literature about project control. A strong emphasis was given to the planning phase: as the schedule serves as a reference for control, Goldratt’s Theory of Constraints – contaminated with elements from flexible methods and frameworks – is adopted to guarantee the baseline a stronger adherence to reality. The schedule higher adherence to reality was validated coupling the interview and the what-if methodology; these provided, respectively, a qualitative and quantitative proof of the effectiveness of the proposed control process. This control process appears to be reliant on a schedule that is more adherent to the events that can occur in reality. The higher accuracy of the schedule allows knowing more accurately which is the level of completeness of the project. By this means, it is sufficient to adopt a simple metric for project control instead of more complex algorithms (which are not always used in the industrial reality). Differently from some approaches such as stochastic and fuzzy logic, the control process is presented as a simple and pragmatic solution that can be adopted for R&amp;D projects aimed at the development of industrial technology, including the construction of a pilot plant and the execution of experimental campaigns