Fast predictive expression platform – CHO-K1 with transposase

The Mammalian Expression group in Therapeutics Discovery Research produces panels of therapeutic candidates in high-throughput (HT) for early stage screening in addition to generating larger productions that are used for manufacturability assessment, pre-clinical PK, and efficacy studies. As our molecule types expand from monoclonal antibodies to include various bispecific modalities, the ability to predict how a molecule will behave in our stable manufacturing host becomes more difficult. To more quickly predict characteristics and manufacturability of our candidate therapeutics, we are developing in-house stable expression systems. The transposase is a mobile genetic element that efficiently transposes between vectors and chromosomes via a “cut and paste” mechanism. Because the transposase facilitates non-random, efficient genetic integration, we investigated the possible incorporation of this technology into our current in-house transient expression vector system. We have observed that its stable-like integration properties provide us with a foundation for enabling a short production time, comparable with a transient expression system, while generating proteins with attributes that are predictive of our manufacturing system. This approach has been validated and implemented with our CHO-K1 stable expression system. With this technology, we are able to reliably generate the diverse array of therapeutic candidate modalities in a high-throughput format while achieving higher predictability of material derived from our manufacturing hosts

Unfamiliar faces engaged in non-rigid motion are processed holistically

Paper presented at the Australasian Experimental Psychology Conference 2015, 8-11 April 2015, Sydney, Australia

Semi-Analytic Galaxy Evolution (SAGE): Model Calibration and Basic Results

This paper describes a new publicly available codebase for modelling galaxy formation in a cosmological context, the "Semi-Analytic Galaxy Evolution" model, or SAGE for short. SAGE is a significant update to that used in Croton et al. (2006) and has been rebuilt to be modular and customisable. The model will run on any N-body simulation whose trees are organised in a supported format and contain a minimum set of basic halo properties. In this work we present the baryonic prescriptions implemented in SAGE to describe the formation and evolution of galaxies, and their calibration for three N-body simulations: Millennium, Bolshoi, and GiggleZ. Updated physics include: gas accretion, ejection due to feedback, and reincorporation via the galactic fountain; a new gas cooling--radio mode active galactic nucleus (AGN) heating cycle; AGN feedback in the quasar mode; a new treatment of gas in satellite galaxies; and galaxy mergers, disruption, and the build-up of intra-cluster stars. Throughout, we show the results of a common default parameterization on each simulation, with a focus on the local galaxy population.Comment: 15 pages, 9 figures, accepted for publication in ApJS. SAGE is a publicly available codebase for modelling galaxy formation in a cosmological context, available at https://github.com/darrencroton/sage Questions and comments can be sent to Darren Croton: [email protected]

Spatial distribution of clinical computer systems in primary care in England in 2016 and implications for primary care electronic medical record databases: a cross-sectional population study.

OBJECTIVES: UK primary care databases (PCDs) are used by researchers worldwide to inform clinical practice. These databases have been primarily tied to single clinical computer systems, but little is known about the adoption of these systems by primary care practices or their geographical representativeness. We explore the spatial distribution of clinical computing systems and discuss the implications for the longevity and regional representativeness of these resources. DESIGN: Cross-sectional study. SETTING: English primary care clinical computer systems. PARTICIPANTS: 7526 general practices in August 2016. METHODS: Spatial mapping of family practices in England in 2016 by clinical computer system at two geographical levels, the lower Clinical Commissioning Group (CCG, 209 units) and the higher National Health Service regions (14 units). Data for practices included numbers of doctors, nurses and patients, and area deprivation. RESULTS: Of 7526 practices, Egton Medical Information Systems (EMIS) was used in 4199 (56%), SystmOne in 2552 (34%) and Vision in 636 (9%). Great regional variability was observed for all systems, with EMIS having a stronger presence in the West of England, London and the South; SystmOne in the East and some regions in the South; and Vision in London, the South, Greater Manchester and Birmingham. CONCLUSIONS: PCDs based on single clinical computer systems are geographically clustered in England. For example, Clinical Practice Research Datalink and The Health Improvement Network, the most popular primary care databases in terms of research outputs, are based on the Vision clinical computer system, used by <10% of practices and heavily concentrated in three major conurbations and the South. Researchers need to be aware of the analytical challenges posed by clustering, and barriers to accessing alternative PCDs need to be removed

Diet of Two Large Sympatric Teleosts, the Ling (Genypterus blacodes) and Hake (Merluccius australis)

Ling and hake are tertiary consumers, and as a result both may have an important structuring role in marine communities. The diets of 2064 ling and 913 hake from Chatham Rise, New Zealand, were determined from examination of stomach contents. Ling was a benthic generalist, and hake a demersal piscivore. The diet of ling was characterised by benthic crustaceans, mainly Munida gracilis and Metanephrops challengeri, and demersal fishes, mainly Macrourids and scavenged offal from fishing vessels. The diet of hake was characterised by teleost fishes, mainly macrourids and merlucciids. Multivariate analyses using distance-based linear models found the most important predictors of diet variability were depth, fish length, and vessel type (whether the sample was collected from a commercial or research vessel) for ling, and fish length and vessel type for hake. There was no interspecific predation between ling and hake, and resource competition was largely restricted to macrourid prey, although the dominant macrourid species predated by ling and hake were different. Cluster analysis of average diet of intraspecific groups of ling and hake confirmed the persistent diet separation. Although size is a central factor in determining ecological processes, similar sized ling and hake had distinctly different foraging ecology, and therefore could influence the ecosystem in different ways, and be unequally affected by ecosystem fluctuations

Sunlight and red to far-red ratio impact germination of tropical montane cloud forest species

Context: Australia’s tropical montane cloud forests (TMCF) exhibit exceptional species richness and endemism. Determinants of regeneration via seed of these species are next to unknown, limiting our ability to quantify and project their vulnerability to climate change. The ratio of red to far-red light (R:FR) has been shown to influence seed germination of many tropical species.Aims: We investigated germination of six previously unstudied TMCF species in relation to the presence or absence of light (light/dark) and light quality (R:FR). We hypothesised that increased R:FR would lead to increased germination and that small-seeded species would be more likely to have a light requirement and be less sensitive to R:FR compared to larger-seeded species.Methods: Sunlight and polyester filters were used to create a gradient of R:FR ranging from 0.1 to 1.14. Seeds were also sown in constant darkness.Key results: Across species we saw varying germination responses. Three of the four smallest-seeded species exhibited an absolute light requirement for germination and did not discriminate between different R:FR. Germination of the small-seeded TMCF endemic Dracophyllum increased exponentially with increasing R:FR. Germination of the largest-seeded species was inhibited by both low and high R:FR, and germination was higher in constant darkness than diurnal light/dark. All six species were able to germinate at remarkably low R:FR values.Conclusions: Light affects seed germination of Australia’s TMCF plant species in a variety of ways.Implications: The findings of this study provide insights into plant recruitment in situ, and the acclimation potential of these species under reduced R:FR predicted for the future

3-D printed bandpass filters with coupled vertically extruded split ring resonators

The additive manufacturing process of multimaterial extrusion offers performance advantages using functional materials including conductors while making accessible the third dimension in the design of electronics. In this work we show that the additional geometrical freedom offered by this technique can be exploited for the design and realisation of filters made of three- dimensional (3D) resonators that exhibit enhanced characteristics. The coupling properties of 3D grounded square split ring resonators (SRRs) are initially explored. We demonstrate by simulations and experiments that SRRs with finite height display significantly stronger coupling compared to equivalent thin printed circuit structures. The observed trend can be exploited for designing filters with wider operational bandwidths for a given footprint, or miniaturized layouts and enhanced compatibility with fabrication limits for minimum feature size and spacing without performance degradation. This concept is demonstrated by presenting results of full-wave simulations for sample bandpass filters with identical footprint but formed by coupled 3D square SRRs of different heights, showing that filters with taller resonators exhibit increasingly wider bandwidths. Two filter prototypes with centre frequencies at 1.6 GHz and 2.45 GHz are manufactured by multimaterial 3D printing. The measured characteristics of these prototypes are found to be in good agreement with numerical simulations taking into account the effect of the lossier metallic and dielectric materials used in 3D printing and confirm the predicted larger bandwidth of the filters made of 3D SRRs with marginally higher insertion losses

Identifying 'avoidable harm' in family practice: A RAND/UCLA Appropriateness Method consensus study

BackgroundHealth care-related harm is an internationally recognized threat to public health. The United Kingdom’s national health services demonstrate that upwards of 90% of health care encounters can be delivered in ambulatory settings. Other countries are transitioning to more family practice-based health care systems, and efforts to understand avoidable harm in these settings is needed.MethodsWe developed 100 scenarios reflecting a range of diseases and informed by the World Health Organization definition of ‘significant harm’. Scenarios included different types of patient safety incidents occurring by commission and omission, demonstrated variation in timeliness of intervention, and conditions where evidence-based guidelines are available or absent. We conducted a two-round RAND / UCLA Appropriateness Method consensus study with a panel of family practitioners in England to define “avoidable harm” within family practice. Panelists rated their perceptions of avoidability for each scenario. We ran a k-means cluster analysis of avoidability ratings.ResultsPanelists reached consensus for 95 out of 100 scenarios. The panel agreed avoidable harm occurs when a patient safety incident could have been probably, or totally, avoided by the timely intervention of a health care professional in family practice (e.g. investigations, treatment) and / or an administrative process (e.g. referrals, alerts in electronic health records, procedures for following up results) in accordance with accepted evidence-based practice and clinical governance. Fifty-four scenarios were deemed avoidable, whilst 31 scenarios were rated unavoidable and reflected outcomes deemed inevitable regardless of family practice intervention. Scenarios with low avoidability ratings (1 s or 2 s) were not represented by the categories that were used to generate scenarios, whereas scenarios with high avoidability ratings (7 s 8 s or 9 s) were represented by these a priori categories.DiscussionThe findings from this RAND/UCLA Appropriateness Method study define the characteristics and conditions that can be used to standardize measurement of outcomes for primary care patient safety.ConclusionWe have developed a definition of avoidable harm that has potential for researchers and practitioners to apply across primary care settings, and bolster international efforts to design interventions to target avoidable patient safety incidents that cause the most significant harm to patients