Arts curriculum implementation: Adopt and adapt as policy translation

This paper examines macro, meso and micro understandings of policy enactment within Western Australian primary school arts education where a new national arts curriculum is being revised and implemented through a process colloquially known as ‘adopt and adapt’. This paper focuses on how a government led implementation policy has influenced arts teaching and learning in unintended ways. It Includes a theoretical reflection and a consideration of the effects of such policies. Using policy enactment theory as the enquiry lens, four contextual variables are highlighted for their impact on teachers and schools. The variables include situated contexts, material contexts, professional cultures and external factors. Effects are discussed through the perspectives of eleven arts curriculum leaders drawn from in-depth semi-structured interviews. Marginalisation of the arts, the disconnection of schools and teachers to the arts and professional learning impacts are discussed as results of this policy translation

Content without context is noise : Looking for curriculum harmony in primary arts education in Western Australia

Arts education in Western Australian primary schools consist of learning opportunities outlined by mandated curriculum. However, assumptions underlying this curriculum involving access, resources and support impact schools’ capacity to implement the curriculum without them being adequately addressed by the written curriculum. Drawing on the policy enactment theory of Ball, Maguire, and Braun (2012), four contextual variables (situated contexts, professional cultures, material contexts and external factors) are used to highlight the differences between the written published curriculum and the implemented, practised curriculum. Drawing on interviews with 24 participants across four schools issues of geographic location, use of arts specialists, appropriate learning spaces and the stresses associated with mandated literacy and numeracy testing are reported as contextual pressures by this study. This paper details the disruptive interference of these contextual pressures that we describe as ‘noise’. The provision of a better understanding of this contextual landscape brings schools and teachers away from the ‘noise’ of disruption and closer to curriculum harmony

Nonlinear time-warping made simple: a step-by-step tutorial on underwater acoustic modal separation with a single hydrophone

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Bonnel, J., Thode, A., Wright, D., & Chapman, R. Nonlinear time-warping made simple: a step-by-step tutorial on underwater acoustic modal separation with a single hydrophone. The Journal of the Acoustical Society of America, 147(3), (2020): 1897, doi:10.1121/10.0000937.Classical ocean acoustic experiments involve the use of synchronized arrays of sensors. However, the need to cover large areas and/or the use of small robotic platforms has evoked interest in single-hydrophone processing methods for localizing a source or characterizing the propagation environment. One such processing method is “warping,” a non-linear, physics-based signal processing tool dedicated to decomposing multipath features of low-frequency transient signals (frequency f  1 km). Since its introduction to the underwater acoustics community in 2010, warping has been adopted in the ocean acoustics literature, mostly as a pre-processing method for single receiver geoacoustic inversion. Warping also has potential applications in other specialties, including bioacoustics; however, the technique can be daunting to many potential users unfamiliar with its intricacies. Consequently, this tutorial article covers basic warping theory, presents simulation examples, and provides practical experimental strategies. Accompanying supplementary material provides matlab code and simulated and experimental datasets for easy implementation of warping on both impulsive and frequency-modulated signals from both biotic and man-made sources. This combined material should provide interested readers with user-friendly resources for implementing warping methods into their own research.This work was supported by the Office of Naval Research (Task Force Ocean, project N00014-19-1-2627) and by the North Pacific Research Board (project 1810). Original warping developments were supported by the French Delegation Generale de l'Armement

The nature of a gravitationally lensed sub-millimetre arc in MS0451.6-0305: two interacting galaxies at z~2.9?

We present a new SCUBA image of the cluster MS0451.6-0305, which exhibits strong, extended sub-mm flux at 850 microns. The most striking feature in the map is an elongated region of bright sub-mm emission, with a flux density of >10 mJy over several beam-sizes. This region is apparently coincident with a previously known optical arc (which turns out to be a strongly lensed Lyman Break Galaxy at z=2.911), as well as with a newly identified multiply-imaged ERO (Extremely Red Object) pair predicted to be at a similar, if not identical redshift. By combing a detailed lensing model with deep images from HST, Chandra, CFHT, JCMT, and spectra from the VLT, we conclude that both the strongly lensed optical arc and ERO systems have properties consistent with known sub-mm emitters. Using a simple model for the two sources, we estimate that the multiply-lensed EROs contribute the majority of the flux in the SCUBA lensed arc. Correcting for the lensing amplification, we estimate that the inherent 850 micron fluxes for both objects are ~0.4 mJy. If the LBG and ERO pair are truly at the same redshift, then they are separated by only ~10 kpc in the source plane, and hence constitute an interacting system at z~2.9. Higher angular resolution observations in sub-mm/mm will permit us to more accurately separate the contribution from each candidate, and better understand the nature of this system.Comment: Accepted for publication in MNRAS. 10 pages, 7 figures (1 in colour). A higher resolution version can be found at http://www.submm.caltech.edu/~borys/papers/ms0451.pd

Out Where the West Begins

https://digitalcommons.library.umaine.edu/mmb-vp/2350/thumbnail.jp

Biotherapeutic development in the \u27Omics Age: The CHO genome and beyond

The Next-Generation Sequencing (NGS) revolution has had a profound effect on the manner in which we approach the fields of biology and medicine, but the effects are not limited to these fields alone. With the process of collecting and analyzing large datasets becoming more seamless, a growing number of disciplines are incorporating NGS and other ‘Omics technologies into their workflow. Biotherapeutic development is one such field that is benefitting from the comprehensive and rich datasets that NGS can provide. At Biogen, we are using NGS in two ways: to provide a deeper understanding CHO cell biology during bioprocessing and to improve our cell line development workflows. A straightforward use of NGS technology is to verify that the biotherapeutic mRNA sequence is free of mutations during clone screening. We developed a method that takes advantage the multiplexing and high-throughput capability of NGS to sequence confirm the mRNA from multiple antibody producing clones in one experiment. Results from these NGS experiments are combined with other product quality and productivity data points to inform clone decisions. A single mutated clone has been identified and subsequently discarded in three separate programs to date. As an additional QC step to minimize the possibility of sequence variants, we have also implemented NGS plasmid confirmation prior to transfection. These two NGS methods are now an integral part of our cell line development workflow and have added quality to the clones moving forwarded for more rigorous screening. Biogen has also made generating, characterizing and annotating the genomic sequence of our CHO host cell lines a priority. To this end, we have partnered with a number of vendor and academic labs to move this initiative forward and arrive at what we believe are industry-leading CHO genomes. Our collaborators utilized a combination of the shorter, more accurate Illumina reads with SMRT technology, commonly called PacBio reads. This work has filled in gaps within our CHO genomes and reduced the number of contigs and scaffolds reported for public genome resources. While the updating and curation of our CHO genomes will continue into the future, the state of these genomes allowed us to explore other ‘Omics techniques we deemed important for characterization of our production clones. Transcriptomics has become a central characterization technique of production clones, giving us a deeper understanding of the CHO cell during production. By comparing RNAseq datasets at various time points during our bioprocess, we have identified changes in cellular pathways as they relate to a particular growth stage. As such, we are aiming to exploit these cellular changes and use them to our advantage in expressing our biotherapeutics. The development of targeted integration strategies has also been a primary goal for us in the ‘Omics space. The ability to specifically target GOIs to multiple safe harbor areas within the CHO genome can offer flexibility for screening expression modifiers as well as accelerate the cell line development process. To identify the integration sites in our production clones, we are using a ‘pull-down’ method to enrich for genome sequences that are abutting the expression vector. Results of these experiments will be discussed. Taken together, Biogen has made ‘Omics a priority to gain a deeper understand of our CHO cell biology at the cell line development stage and during the production bioreactor cultures. We are now taking meaningful steps forward, and believe that ‘Omics will continue to shape how we engineering, select and culture CHO cells expressing our biotherapeutics

How can we best chart children’s growth in the paperless age? The UK experience

Growth charts have played an integral part in the monitoring and assessment of children’s health for the past 50 years, but their use is now under threat as paperless electronic systems become more widely used. While the obvious solution is to adopt electronic charting systems, this can prove challenging in practice. This article describes the key issues to consider in planning this transition and the charting options available, ranging from bespoke local systems to commercial packages and a new initiative by the Royal College of Paediatrics and Child Health

Producer cell line engineering for large volume manufacturing of therapeutic Aav

Recombinant adeno-associated viruses (rAAV) remain one of the most promising gene therapy vectors for patients with genetic abnormalities. rAAV can safely deliver long-lasting expression of a therapeutic transgene. To create a rAAV virus the wild-type viral genome is replaced with a functional transgene expression cassette. A constitutive promoter can be utilized to drive strong expression of the transgene once the rAAV vector has infected the target cell. Unlike wtAAV, the recombinant vector avoids the pitfalls of genomic integration by establishing extrachomosomal episomes or concatemers. Multiple studies have shown that rAAV can provide sustained expression of the transgene in cultured cells and pre-clinical models, providing evidence that rAAV could offer a cure for certain diseases. Bioengineering advancements have expanded the viral tropism beyond the constraints of naturally occurring AAV capsids, increasing the types of cells that can be thought of as targets. Taken together, rAAV therapies have attractive qualities to safely address the needs of patients where protein or small molecule therapies would fall short. One challenge with therapeutic rAAV is the ability to generate enough virus for clinical trials and commercial supply. This is particularly true with neuromuscular or hemophilia patients in which doses can exceed 1 x 1014 viral genomes per patient. Typical yields from a rAAV production are around 104 viral genomes per cell, meaning 1010 cells will be needed for a single dose. This amount of therapeutic virus is a challenge to deliver with standard gene therapy production platforms, and will require a production platform that can reliably generate sufficient quantities of therapeutic rAAV to meet patient demand. Biogen has selected the producer cell line (PCL) platform to meet the large demand for therapeutic rAAV. Producer cell lines are generated by stably integrating the AAV viral genes along with the ITR flanked therapeutic gene of interest into a host cell line. rAAV production is then triggered by the addition of a ‘helper virus’ to provide functional genes for AAV replication. Traditional PCL platforms have used HeLa cells as the host and Adenovirus type-5 to deliver helper functions. We have used this platform as a basis for further development. Presented here will be our rationale for selecting the PCL platform, improvements made to the platform for ongoing clinical support, and our vision for the next generation PCL platform

Rheumatoid arthritis synovial fluid neutrophils drive inflammation through production of chemokines, reactive oxygen species and neutrophil extracellular traps

ABSTRACT Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Neutrophils are believed to play an important role in both the initiation and progression of RA, and large numbers of activated neutrophils are found within both synovial fluid (SF) and synovial tissue from RA joints. In this study we analysed paired blood and SF neutrophils from patients with severe, active RA (DAS28> 5.1, n=3) using RNA-seq. 772 genes were significantly different between blood and SF neutrophils. IPA analysis predicted that SF neutrophils had increased expression of chemokines and ROS production, delayed apoptosis, and activation of signalling cascades regulating the production of NETs. This activated phenotype was confirmed experimentally by incubating healthy control neutrophils in cell-free RA SF, which was able to delay apoptosis and induce ROS production in both unprimed and TNF α primed neutrophils (p< 0.05). RA SF significantly increased neutrophil migration through 3mM transwell chambers (p< 0.05) and also increased production of NETs by healthy control neutrophils, including exposure of myeloperoxidase (MPO) and citrullinated histone-H3-positive DNA NETs. IPA analysis predicted NET production was mediated by signalling networks including AKT, RAF1, SRC and NF- κ B. Our results expand the understanding of the molecular changes that take place in the neutrophil transcriptome during migration into inflamed joints in RA, and the altered phenotype in RA SF neutrophils. Specifically, RA SF neutrophils lose their migratory properties, residing within the joint to generate signals that promote joint damage, as well as inflammation via recruitment and activation of both innate and adaptive immune cells. We propose that this activated SF neutrophil phenotype contributes to the chronic inflammation and progressive damage to cartilage and bone observed in patients with RA

Limits of ultra-high-precision optical astrometry: Stellar surface structures

We investigate the astrometric effects of stellar surface structures as a practical limitation to ultra-high-precision astrometry, e.g. in the context of exoplanet searches, and to quantify the expected effects in different regions of the HR-diagram. Stellar surface structures are likely to produce fluctuations in the integrated flux and radial velocity of the star, as well as a variation of the observed photocentre, i.e. astrometric jitter, and closure phase. We use theoretical considerations supported by Monte Carlo simulations to derive statistical relations between the corresponding astrometric, photometric, and radial-velocity effects. For most stellar types the astrometric jitter due to stellar surface structures is expected to be of order 10 micro-AU or greater. This is more than the astrometric displacement typically caused by an Earth-size exoplanet in the habitable zone, which is about 1-4 micro-AU for long-lived main-sequence stars. Only for stars with extremely low photometric variability (<0.5 mmag) and low magnetic activity, comparable to that of the Sun, will the astrometric jitter be of order 1 micro-AU, suffcient to allow the astrometric detection of an Earth-sized planet in the habitable zone. While stellar surface structure may thus seriously impair the astrometric detection of small exoplanets, it has in general negligible impact on the detection of large (Jupiter-size) planets and on the determination of stellar parallax and proper motion. From the starspot model we also conclude that the commonly used spot filling factor is not the most relevant parameter for quantifying the spottiness in terms of the resulting astrometric, photometric and radial-velocity variations.Comment: 12 pages, 4 figures, submitted to A&