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To report trends in prevalence of singleton pregnancies affected with congenital anomalies in Scotland between 2000 and 2017 and the 15-year survival rates of affected singleton live born children.

Homozygous mutation of the Csf1r locus (Csf1rko) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis of the mechanisms underlying the phenotypic impacts of Csf1r mutation, we bred a rat Csf1rko allele to the inbred dark agouti (DA) genetic background and to a Csf1r-mApple reporter transgene. The Csf1rko led to almost complete loss of embryonic macrophages and ablation of most adult tissue macrophage populations. We extended previous analysis of the Csf1rko phenotype to early postnatal development to reveal impacts on musculoskeletal development and proliferation and morphogenesis in multiple organs. Expression profiling of 3-week old wild-type (WT) and Csf1rko livers identified 2760 differentially expressed genes associated with the loss of macrophages, severe hypoplasia, delayed hepatocyte maturation, disrupted lipid metabolism and the IGF1/IGF binding protein system. Older Csf1rko rats developed severe hepatic steatosis. Consistent with the developmental delay in the liver Csf1rko rats had greatly-reduced circulating IGF1. Transfer of WT bone marrow (BM) cells at weaning without conditioning repopulated resident macrophages in all organs, including microglia in the brain, and reversed the mutant phenotypes enabling long term survival and fertility. WT BM transfer restored osteoclasts, eliminated osteopetrosis, restored bone marrow cellularity and architecture and reversed granulocytosis and B cell deficiency. Csf1rko rats had an elevated circulating CSF1 concentration which was rapidly reduced to WT levels following BM transfer. However, CD43hi non-classical monocytes, absent in the Csf1rko, were not rescued and bone marrow progenitors remained unresponsive to CSF1. The results demonstrate that the Csf1rko phenotype is autonomous to BM-derived cells and indicate that BM contains a progenitor of tissue macrophages distinct from hematopoietic stem cells. The model provides a unique system in which to define the pathways of development of resident tissue macrophages and their local and systemic roles in growth and organ maturation., Author summary Monocytes and macrophages are cells of the innate immune system produced by the bone marrow that can be recruited into tissues to support defense against infection and repair following injury. So-called resident macrophages are abundant in every tissue in the body. Their numbers are controlled by a hormone-like growth factor called macrophage colony-stimulating factor (CSF1). Mutations in the surface receptor (CSF1R) that enables macrophages to respond to CSF1 lead to the loss of tissue macrophages. Human patients born with CSF1R mutations may die in infancy or suffer severe developmental abnormalities in the skeleton and brain. In this study we report the effects of the loss of tissue macrophages on postnatal growth and development in a rat model of CSF1R deficiency. In this model there was a global loss of resident macrophages, severe postnatal growth defects, failure of development of multiple organs including the liver and early death. The effects of the mutation could be rescued completely by transfer of normal bone marrow cells into the peritoneal cavity at weaning permitting long term survival and even fertility. The results indicate that postnatal expansion of tissue macrophage populations is essential for normal development.

Elimination of reference mapping bias reveals robust immune related allele-specific expression in crossbred sheepMazdak Salavati 1, Stephen J. Bush 1, Sergio Palma-Vera 2, Mary E.B. McCulloch 1, David A. Hume 3 and Emily L. Clark 1The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UKLeibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyMater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, Qld 4102, Australia * Correspondence: Emily.Clark@roslin.ed.ac.uk Mazdak.Salavati@roslin.ed.ac.uk

Chosen names reflect changes in societal values, personal tastes and cultural diversity. Vogues in name usage can be easily shown on a case by case basis, by plotting the rise and fall in their popularity over time. However, individual name choices are not made in isolation and trends in naming are better understood as group-level phenomena. Here we use network analysis to examine onomastic (name) datasets in order to explore the influences on name choices within the UK over the last 170 years. Using a large representative sample of approximately 22 million forenames from England and Wales given between 1838 and 2014, along with a complete population sample of births registered between 1996 and 2016, we demonstrate how trends in name usage can be visualised as network graphs. By exploring the structure of these graphs various patterns of name use become apparent, a consequence of external social forces, such as migration, operating in concert with internal mechanisms of change. In general, we show that the topology of network graphs can reveal naming vogues, and that naming vogues in part reflect social and demographic changes. Many name choices are consistent with a self-correcting feedback loop, whereby rarer names become common because there are virtues perceived in their rarity, yet with these perceived virtues lost upon increasing commonality. Towards the present day, we can speculate that the comparatively greater range of media, freedom of movement, and ability to maintain globally-distributed social networks increases the number of possible names, but also ensures they may more quickly be perceived as commonplace. Consequently, contemporary naming vogues are relatively short-lived with many name choices appearing a balance struck between recognisability and rarity. The data are available in multiple forms including via an easy-to-use web interface at http://demos.flourish.studio/namehistory.

Regular ‘revalidation’ of medical registration has been proposed as a way to ‘affirm or establish the continuing competence of physicians’ whilst strengthening and facilitating ethical and professional ‘commitment to reducing errors, adhering to best practice and improving quality of care’ by the medical profession. This project examines revalidation and its potential policy implications through the lens of the Australian general public's attitudes towards it. We designed a Discrete Choice Experiment to elicit information regarding this proposed regulatory reform from the Australian general public.

Variance in expression estimates arising from differential transcriptome sampling by polyA+ and ribo-minus RNA selection methods. Figure S2. Variance in TPM estimates by differential transcriptome sampling was effectively negated by the combined use of a filtered reference transcriptome for quantifying expression, and applying a ratio-based correction to the TPM estimates of ribo-minus libraries. Figure S3. Reduction in the absolute difference in TPM estimates from polyA+ and ribo-minus libraries when applying a ratio-based correction to the latter. Figure S4. Tissue tree constructed from the Euclidean distances between uncorrected TPM vectors for two human RNA-seq datasets sequenced with either polyA+ or ribo-minus libraries. Figure S5. Tissue tree constructed from the Euclidean distances between corrected TPM vectors for two human RNA-seq datasets sequenced with either polyA+ or ribo-minus libraries. Figure S6. Comparison of TPM estimates in the adrenal gland, as generated for 19,716 human genes using both polyA-selected and rRNA-depleted libraries. Figure S7. Comparison of TPM estimates in the liver, as generated for 19,716 human genes using both polyA-selected and rRNA-depleted libraries. Figure S8. Comparison of TPM estimates in the ovary, as generated for 19,716 human genes using both polyA-selected and rRNA-depleted libraries. Figure S9. Comparison of TPM estimates in the sigmoid colon, as generated for 19,716 human genes using both polyA-selected and rRNA-depleted libraries. Figure S10. Comparison of TPM estimates in the spleen, as generated for 19,716 human genes using both polyA-selected and rRNA-depleted libraries. Figure S11. Comparison of TPM estimates in the testis, as generated for 19,716 human genes using both polyA-selected and rRNA-depleted libraries. (DOCX 709 kb)

Optimal block designs for additive models achieve their efficiency by dividing experimental units among relatively homogenous blocks and allocating treatments equally to blocks. Responses in many modern experiments, however, are drawn from distributions such as the one- and two-parameter exponential families, e.g., RNA sequence counts from a negative binomial distribution. These violate additivity. Yet, designs generated by assuming additivity continue to be used, because better approaches are not available, and because the issues are not widely recognised. We solve this problem for single-factor experiments in which treatments, taking categorical values only, are arranged in blocks and responses drawn from a Poisson distribution. We derive expressions for two objective functions, based on D_A- and C-optimality, with efficient estimation of linear contrasts of the fixed effects parameters in a Poisson generalised linear mixed model (GLMM) being the objective. These objective functions are shown to be computational efficient, requiring no matrix inversion. Using simulated annealing to generate Poisson GLMM-based locally optimal designs, we show that the replication numbers of treatments in these designs are inversely proportional to the relative magnitudes of the treatments' expected counts. Importantly, for non-negligible treatment effect sizes, Poisson GLMM-based optimal designs may be substantially more efficient than their classically optimal counterparts.

Bush, Stephen P., Madden, Hannah (2013): Preliminary checklist of the bees of St. Eustatius, Lesser Antilles (Hymenoptera: Apoidea: Anthophila). Insecta Mundi 2013 (298): 1-3, DOI: http://doi.org/10.5281/zenodo.5175937, {"references":["Bland, R. G., and L. Desutter-Grandcolas. 2003. An annotated list of Orthoptera from St. Eustatius and Saba, Dutch West Indies, with descriptions of two new cricket species (Trigonidiidae, Mogoplistidae). Journal of Orthoptera Research 12: 115-126.","Brooks, R. W. 1999. Bees of the genus Anthophora Latreille 1803 (Hymenoptera Apidae Anthophorini) of the West Indies. Tropical Zoology 12: 105-124.","Genaro, J. A., and N. M. Franz. 2008. Bees of greater Puerto Rico (Hymenoptera: Apoidea: Anthophila). Insecta Mundi 0040: 1-24.","Freitas, B. M., V. L. Imperatriz-Fonseca, L. M. Medina, A. de Matos Peixoto Kleinert, L. Galetto, G. Nates-Parra, and J. J. G. Quezada-Euan. 2009. Diversity, threats, and conservation of native bees in the Neotropics. Apidologie 40: 332-346.","Myers, N., R. A. Mittermeier, C. G. Mittermeier, G. A. B. da Fonseca, and J. Kent. 2000. Biodiversity hotspots for conservation priorities. Nature 403: 853-858.","Moure, J. S. 2012. Xylocopini Latreille, 1802. In: J. S. Moure, D. Urban, and G. A. R. Melo (Orgs). Catalogue of bees (Hymenoptera, Apoidea) in the Neotropical Region - online version. Available at http://www.moure.cria.org.br/catalogue. Accessed Jan/31/2013.","Received March 20, 2013; Accepted April 19, 2013."]}

We present progress on the experimental validation of a fundamental and universally applicable vulnerability analysis framework that is capable of identifying new types of vulnerabilities before attackers innovate attacks. This new framework proactively identifies system components that are vulnerable based upon their Kolmogorov Complexity estimates and it facilitates prediction of previously unknown vulnerabilities that are likely to be exploited by future attack methods. A tool that utilizes a growing library of complexity estimators is presented. This work is an incremental step towards validation of the concept of complexity-based vulnerability analysis. In particular, results indicate that data types (semantic types) can be identified by estimates of their complexity. Thus, a map of complexity can identify suspicious types, such as executable data embedded within passive data types, without resorting to predefined headers, signatures, or other limiting a priori information.

A fundamental understanding of gain provided by motion prediction in wireless ad hoc routing is currently lacking. This paper examines benefits in routing obtainable via prediction. A theoretical best-case non-predictive routing model is quantified in terms of both message overhead and update time for non-predictive routing. This best- case model of existing routing performance is compared with predictive routing. Several specific instances of predictive improvements in routing are examined. The primary contribution of this paper is quantification of predictive gain for wireless ad hoc routing., Comment: Introduces flash routing

This research concentrates on the design and analysis of an algorithm referred to as Virtual Network Configuration (VNC) which uses predicted future states of a system for faster network configuration and management. VNC is applied to the configuration of a wireless mobile ATM network. VNC is built on techniques from parallel discrete event simulation merged with constraints from real-time systems and applied to mobile ATM configuration and handoff. Configuration in a mobile network is a dynamic and continuous process. Factors such as load, distance, capacity and topology are all constantly changing in a mobile environment. The VNC algorithm anticipates configuration changes and speeds the reconfiguration process by pre-computing and caching results. VNC propagates local prediction results throughout the VNC enhanced system. The Global Positioning System is an enabling technology for the use of VNC in mobile networks because it provides location information and accurate time for each node. This research has resulted in well defined structures for the encapsulation of physical processes within Logical Processes and a generic library for enhancing a system with VNC. Enhancing an existing system with VNC is straight forward assuming the existing physical processes do not have side effects. The benefit of prediction is gained at the cost of additional traffic and processing. This research includes an analysis of VNC and suggestions for optimization of the VNC algorithm and its parameters., Comment: PhD Thesis

This paper introduces a novel algorithm, the Active Virtual Network Management Protocol (AVNMP), for predictive network management. It explains how the AVNMP facilitates the management of an active network by allowing future predicted state information within an active network to be available to network management algorithms. This is accomplished by coupling ideas from optimistic discrete event simulation with active networking. The optimistic discrete event simulation method used is a form of self-adjusting Time Warp. It is self-adjusting because the system adjusts for predictions which are inaccurate beyond a given tolerance. The concept of a streptichron and autoanaplasis are introduced as mechanisms which take advantage of the enhanced flexibility and intelligence of active packets. Finally, it is demonstrated that the AVNMP is a feasible concept., Comment: presented at PADS'99

There is a trend toward the use of predictive systems in communications networks. At the systems and network management level predictive capabilities are focused on anticipating network faults and performance degradation. Simultaneously, mobile communication networks are being developed with predictive location and tracking mechanisms. The interactions and synergies between these systems present a new set of problems. A new predictive network management framework is developed and examined. The interaction between a predictive mobile network and the proposed network management system is discussed. The Rapidly Deployable Radio Network is used as a specific example to illustrate these interactions.