Leveraging Summary Statistics to Make Inferences about Complex Phenotypes in Large Biobanks

As genetic sequencing becomes less expensive and data sets linking genetic data and medical records (e.g., Biobanks) become larger and more common, issues of data privacy and computational challenges become more necessary to address in order to realize the benefits of these datasets. One possibility for alleviating these issues is through the use of already-computed summary statistics (e.g., slopes and standard errors from a regression model of a phenotype on a genotype). If groups share summary statistics from their analyses of biobanks, many of the privacy issues and computational challenges concerning the access of these data could be bypassed. In this paper we explore the possibility of using summary statistics from simple linear models of phenotype on genotype in order to make inferences about more complex phenotypes (those that are derived from two or more simple phenotypes). We provide exact formulas for the slope, intercept, and standard error of the slope for linear regressions when combining phenotypes. Derived equations are validated via simulation and tested on a real data set exploring the genetics of fatty acids

The Role Modelling and Farming Systems Research Can Play in Redesigning Grazing Systems for Improved Productivity and Environmental Sustainability

Achieving production and natural resource outcomes from farming systems is critical with growing demand for livestock products, increasing pressure on land and water resources and the desire of farmers to improve profit and standard of living. In many countries this brings to the fore a number of policy dilemmas and conflicts in terms of pastoral household livelihood, regional economic growth and development, as well as natural resource management. By using two case studies; (1) Temperate Grasslands in Southern Australia (EverGraze project); and (2) Western Grasslands in North West China (ACIAR project), this paper considers how farming systems can be redesigned for production and environmental outcomes using modelling and farming systems research. Farming systems, as well as the regions and economies in which they operate, are complex and under constant change. The use of models combined with good science, relevant data and regional validation is essential to examine alternative systems that are better suited to changed operating conditions. Bio-economic modelling helps to understand trade-offs between production and enterprise performance and environmental sustainability over time and, most importantly, where multiple benefits from farming systems are possible. We contend that it is possible to redesign farming systems with both enterprise and environmental sustainability in mind. However the approach used to design and test alternative farming systems is important in an era of declining research resources and increasing complexity

EverGraze: A Partnership between Researchers, Farmers and Advisors to Deliver Effective Grassland Management

The profitable and sustainable management of livestock production from grassland systems is challenging and it can be difficult to develop a research structure that addresses farmer’s needs and has acceptable rigour and on-ground impact. This paper describes the attributes of research, development and extension (RD&E) programs that are required for a successful partnership between researchers, farmers and advisors. Insights are provided from the EverGraze program that designed, tested and implemented farming systems based on perennial pastures across southern Australia. With this project farmers and advisors were involved in setting research direction, designing experiments, providing strategic guidance over the management of the systems experiments and then the synthesis of regionally applicable key messages. This involvement ensured the relevance of the research and aided in the extension and uptake of the information. The result has been an effective partnership between researchers, farmers and advisors that had a high level of impact across the high rainfall zone (HRZ) of southern Australia, with 1950 farmers or ~8% of those in the HRZ documented as having changed practice over an area of 816,000 ha over a five year period (2009 to 2014)

Chitosan-zein nano-in-microparticles Capable of Mediating in vivo Transgene Expression Following Oral Delivery

The oral route is an attractive delivery route for the administration of DNA-based therapeutics, specifically for applications in gene therapy and DNA vaccination. However, oral DNA delivery is complicated by the harsh and variable conditions encountered throughout gastrointestinal (GI) transit, leading to degradation of the delivery vector and DNA cargo, and subsequent inefficient delivery to target cells. In this work, we demonstrate the development and optimization of a hybrid-dual particulate delivery system consisting of two natural biomaterials, zein (ZN) and chitosan (CS), to mediate oral DNA delivery. Chitosan-Zein Nano-in-Microparticles (CS-ZN-NIMs), consisting of core Chitosan/DNA nanoparticles (CS/DNA NPs) prepared by ionic gelation with sodium tripolyphosphate (TPP), further encapsulated in ZN microparticles, were formulated using a water-in-oil emulsion (W/O). The resulting particles exhibited high CS/DNA NP loading and encapsulation within ZN microparticles. DNA release profiles in simulated gastric fluid (SGF) were improved compared to un-encapsulated CS/ DNA NPs. Further, site-specific degradation of the outer ZN matrix and release of transfection competent CS/ DNA NPs occurred in simulated intestinal conditions with CS/DNA NP cores successfully mediating transfection in vitro. Finally, CS-ZN-NIMs encoding GFP delivered by oral gavage in vivo induced the production of anti-GFP IgA antibodies, demonstrating in vivo transfection and expression. Together, these results demonstrate the successful formulation of CS-ZN-NIMs and their potential to improve oral gene delivery through improved protection and controlled release of DNA cargo

Development of a Quantitative Bead Capture Assay for Soluble IL-7 Receptor Alpha in Human Plasma

IL-7 is an essential cytokine in T-cell development and homeostasis. It binds to the IL-7R receptor, a complex of the IL-7Rα (CD127) and common γ (CD132) chains. There is significant interest in evaluating the expression of CD127 on human T-cells as it often decreased in medical conditions leading to lymphopenia. Previous reports showed the usefulness of CD127 as a prognostic marker in viral infections such as HIV, CMV, EBV and HCV. A soluble CD127 (sCD127) is released in plasma and may contribute to disease pathogenesis through its control on IL-7 activities. Measuring sCD127 is important to define its role and may complement existing markers used in lymphopenic disease management. We describe a new quantitative assay for the measurement of sCD127 in plasma and report sCD127 concentrations in healthy adults.We developed a quantitative bead-based sCD127 capture assay. Polyclonal CD127-specific antibodies were chosen for capture and a biotinylated monoclonal anti-CD127 antibody was selected for detection. The assay can detect native sCD127 and recombinant sCD127 which served as the calibrator. The analytical performance of the assay was characterized and the concentration and stability of plasma sCD127 in healthy adults was determined. The assay's range was 3.2–1000 ng/mL. The concentration of plasma sCD127 was 164±104 ng/mL with over a log variation between subjects. Individual sCD127 concentrations remained stable when measured serially during a period of up to one year.This is the first report on the quantification of plasma sCD127 in a population of healthy adults. Soluble CD127 plasma concentrations remained stable over time in a given individual and sCD127 immunoreactivity was resistant to repeated freeze-thaw cycles. This quantitative sCD127 assay is a valuable tool for defining the potential role of sCD127 in lymphopenic diseases

Reflections on the 'History and Historians' of the black woman's role in the community of slaves: enslaved women and intimate partner sexual violence

Taking as points of inspiration Peter Parish’s 1989 book, Slavery: History and Historians, and Angela Davis’s seminal 1971 article, “Reflections on the black woman’s role in the community of slaves,” this probes both historiographically and methodologically some of the challenges faced by historians writing about the lives of enslaved women through a case study of intimate partner violence among enslaved people in the antebellum South. Because rape and sexual assault have been defined in the past as non-consensual sexual acts supported by surviving legal evidence (generally testimony from court trials), it is hard for historians to research rape and sexual violence under slavery (especially marital rape) as there was no legal standing for the rape of enslaved women or the rape of any woman within marriage. This article suggests enslaved women recognized that black men could both be perpetrators of sexual violence and simultaneously be victims of the system of slavery. It also argues women stoically tolerated being forced into intimate relationships, sometimes even staying with “husbands” imposed upon them after emancipation

The socio-economic gradient in children’s reading skills and the role of genetics

By the time children leave primary school there is a large socio-economic gap in their reading proficiency. There are a number of potential explanations for this socio-economic gap and in this paper we investigate the role of three particular genes and geneenvironment interactions in determining children’s reading skills, using the Avon Longitudinal Study of Parents and Children (ALSPAC) dataset. We find that whilst these genes are indeed correlated with reading outcomes, effect sizes are small and sensitive to the choice of test used and the sample selected. Our results suggest that the leading candidate genes can jointly explain just 2% of the socio-economic gap in children’s reading test scores. We conclude that the influence of these three genes on children’s reading ability is limited, and their role in producing socio-economic gaps in reading ability is even more limited still

Art Opening Minds: Single vs. Multiple Perspectives in Film

A common philosophical assumption is that art can open people’s minds. According to Aesthetic Cognitivism, art is valuable insofar as it provides new perspectives, reframing and reshaping our experience and perception of the world. However, this conceptual claim has not yet been explored empirically. To test this idea, the present study investigates the cognitive effects of watching films. We will test the hypothesis that narrative films embodying multiple perspectives on the same events enhance characteristics of open-mindedness relative to works embodying a single, dominant perspective. Participants will be asked to watch a segment of a film that includes the perspective of multiple characters on the same event (‘Jackie Brown’) either from a single perspective or multiple perspectives. Participants’ open-mindedness will be assessed through four empirical indicators (i.e., creativity, imaginability, cognitive flexibility, openness to new evidence). In addition, we will test whether attentional and affective responses modulate changes in open-mindedness. Allocation of attention to characters or parts of a scene will be established by eye-tracking; arousal will be measured by pupil dilation, electrodermal activity and heart rate. Finally, we also explore the relationship between the participants’ film expertise level and trait open-mindedness (openness to experience) as well as the four measures of open-mindedness and online measures

My Friend the Customer

Your customer must speak with one voice … if that is not the case you will suffer Chet Hendrickson [2]. The Customer is the only non-developer role in eXtreme Programming (XP). The Customer’s explicit responsibilities are to drive the project, providing project requirements (user stories) and quality control (acceptance testing). Unfortunately the customer must also shoulder a number of implicit responsibilities including liaison with external project stakeholders, especially project funders, clients, and end users, while maintaining the trust of both the development team and the wider business. In this paper, we provide a small collection of patterns that that describe useful models for the customer, showing how other roles involved in the process can be adapted to also serve as the XP customer