Implementing a rapid fetal exome sequencing service: What do parents and health professionals think?

OBJECTIVES: Prenatal exome sequencing (pES) for the diagnosis of fetal abnormalities is being introduced more widely in clinical practice. Here we explore parents' and professionals' views and experiences of pES, to identify perceived benefits, concerns, and support needs. METHODS: Semi-structured interviews were conducted with 11 parents and 20 health professionals (fetal medicine and clinical genetics) with experience of rapid pES prior to implementation in the English National Health Service. Interviews were transcribed verbatim and analysed thematically. RESULTS: Parents and professionals were largely positive about pES, emphasising clinical and psychosocial benefits of a timely, definitive diagnosis in pregnancy. Concerns included parental anxiety related to the timing of pES results or uncertain findings, a need for guidelines for case selection and reporting, and ensuring sufficient capacity for counselling, phenotyping and variant interpretation. Professionals were concerned non-genetics professionals may not be equipped to counsel parents on the complexities of pES. CONCLUSION: These findings highlight important issues for clinical implementation of pES. Expert counselling is required to enable parents to make informed decisions during a stressful time. To achieve this, professionals need further education and training, and fetal medicine and genetics services must work closely together to ensure parental understanding and appropriate support

Історична наука в УРСР як предмет дослідження в англо-американській історіографії

У статті відтворено образ історичної науки в УРСР у працях англо-американських учених другої половини ХХ – початку ХХІ ст. Вивчено еволюцію ролі та функцій трьох основних акторів історіографічного процесу в Радянському Союзі – влади, істориків та пересічних громадян. Визначено сталі та змінні компоненти у загальній схемі їх взаємодії.In the article the image of historical science in the Ukrainian SSR in the works of the Anglo-American researchers published during the second half of the twentieth and the beginning of the twenty-first centuries is reconstructed. The modification of roles and functions of three main actors in Soviet historiographical process – power, historians and average citizens – is examined. The invariable and change components in the general pattern of its interaction are defined

Evolving a predator-prey ecosystem of mathematical expressions with grammatical evolution

This is the accepted version of the following article: Alfonseca, M. and Soler Gil, F. J. (2015), Evolving a predator–prey ecosystem of mathematical expressions with grammatical evolution. Complexity, 20: 66–83, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/cplx.21507/abstractThis article describes the use of grammatical evolution to obtain a predator–prey ecosystem of artificial beings associated with mathematical functions, whose fitness is also defined mathematically. The system supports the simultaneous evolution of several ecological niches and through the use of standard measurements, makes it possible to explore the influence of the number of niches and the values of several parameters on “biological” diversity and similar functions. Sensitivity analysis tests have been made to find the effect of assigning different constant values to the genetic parameters that rule the evolution of the system and the predator–prey interaction or of replacing them by functions of time. One of the parameters (predator efficiency) was found to have a critical range, outside which the ecologies are unstable; two others (genetic shortening rate and predator–prey fitness comparison logistic amplitude) are critical just at one side of the range), the others are not critical. The system seems quite robust, even when one or more parameters are made variable during a single experiment, without leaving their critical ranges. Our results also suggest that some of the features of biological evolution depend more on the genetic substrate and natural selection than on the actual phenotypic expression of that substrat

Implementing a rapid fetal exome sequencing service: What do parents and health professionals think?

OBJECTIVES: Prenatal exome sequencing (pES) for the diagnosis of fetal abnormalities is being introduced more widely in clinical practice. Here we explore parents' and professionals' views and experiences of pES, to identify perceived benefits, concerns, and support needs. METHODS: Semi-structured interviews were conducted with 11 parents and 20 health professionals (fetal medicine and clinical genetics) with experience of rapid pES prior to implementation in the English National Health Service. Interviews were transcribed verbatim and analysed thematically. RESULTS: Parents and professionals were largely positive about pES, emphasising clinical and psychosocial benefits of a timely, definitive diagnosis in pregnancy. Concerns included parental anxiety related to the timing of pES results or uncertain findings, a need for guidelines for case selection and reporting, and ensuring sufficient capacity for counselling, phenotyping and variant interpretation. Professionals were concerned non-genetics professionals may not be equipped to counsel parents on the complexities of pES. CONCLUSION: These findings highlight important issues for clinical implementation of pES. Expert counselling is required to enable parents to make informed decisions during a stressful time. To achieve this, professionals need further education and training, and fetal medicine and genetics services must work closely together to ensure parental understanding and appropriate support

Wide-band profile domain pulsar timing analysis

We extend profile domain pulsar timing to incorporate wide-band effects such as frequencydependent profile evolution and broad-band shape variation in the pulse profile. We also incorporate models for temporal variations in both pulse width and in the separation in phase of the main pulse and interpulse. We perform the analysis with both nested sampling and Hamiltonian Monte Carlo methods. In the latter case, we introduce a new parametrization of the posterior that is extremely efficient in the low signal-to-noise regime and can be readily applied to a wide range of scientific problems. We apply this methodology to a series of simulations, and to between seven and nine years of observations for PSRs J1713+0747, J1744-1134 and J1909-3744 with frequency coverage that spans 700-3600 Mhz. We use a smooth model for profile evolution across the full frequency range, and compare smooth and piecewise models for the temporal variations in dispersion measure (DM). We find that the profile domain framework consistently results in improved timing precision compared to the standard analysis paradigm by as much as 40 per cent for timing parameters. Incorporating smoothness in the DM variations into the model further improves timing precision by as much as 30 per cent. For PSR J1713+0747, we also detect pulse shape variation uncorrelated between epochs, which we attribute to variation intrinsic to the pulsar at a level consistent with previously published analyses. Not accounting for this shape variation biases the measured arrival times at the level of ~30 ns, the same order of magnitude as the expected shift due to gravitational waves in the pulsar timing band

Lunar Surface Systems Supportability Technology Development Roadmap

The Lunar Surface Systems Supportability Technology Development Roadmap is a guide for developing the technologies needed to enable the supportable, sustainable, and affordable exploration of the Moon and other destinations beyond Earth. Supportability is defined in terms of space maintenance, repair, and related logistics. This report considers the supportability lessons learned from NASA and the Department of Defense. Lunar Outpost supportability needs are summarized, and a supportability technology strategy is established to make the transition from high logistics dependence to logistics independence. This strategy will enable flight crews to act effectively to respond to problems and exploit opportunities in an environment of extreme resource scarcity and isolation. The supportability roadmap defines the general technology selection criteria. Technologies are organized into three categories: diagnostics, test, and verification; maintenance and repair; and scavenge and recycle. Furthermore, "embedded technologies" and "process technologies" are used to designate distinct technology types with different development cycles. The roadmap examines the current technology readiness level and lays out a four-phase incremental development schedule with selection decision gates. The supportability technology roadmap is intended to develop technologies with the widest possible capability and utility while minimizing the impact on crew time and training and remaining within the time and cost constraints of the program

Commensal discovery of four fast radio bursts during Parkes Pulsar Timing Array observations

The Parkes Pulsar Timing Array (PPTA) project monitors two dozen millisecond pulsars (MSPs) in order to undertake a variety of fundamental physics experiments using the Parkes 64-m radio telescope. Since 2017 June, we have been undertaking commensal searches for fast radio bursts (FRBs) during the MSP observations. Here, we report the discovery of four FRBs (171209, 180309, 180311, and 180714). The detected events include an FRB with the highest signal-to-noise ratio ever detected at the Parkes Observatory, which exhibits unusual spectral properties. All four FRBs are highly polarized. We discuss the future of commensal searches for FRBs at Parkes

TG‐69: Radiographic film for megavoltage beam dosimetry

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134818/1/mp6779.pd

Unraveling Molecular Signatures of Immunostimulatory Adjuvants in the Female Genital Tract through Systems Biology

Sexually transmitted infections (STIs) unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome data determined which signature pathways, processes and networks are shared by or otherwise exclusive to these 2 classes of experimental vaginal adjuvants in the mouse vagina. To our knowledge, this is the first integrated genome-wide transcriptome analysis of the effects of immunomodulatory adjuvants on the female genital tract of a mammal. These results could inform rational development of effective mucosal adjuvants for vaccination against STIs