Evaluation of 3D Printed Immobilisation Shells for Head and Neck IMRT

This paper presents the preclinical evaluation of a novel immobilization system for patients undergoing external beam radiation treatment of head and neck tumors. An immobilization mask is manufactured directly from a 3-D model, built using the CT data routinely acquired for treatment planning so there is no need to take plaster of Paris moulds. Research suggests that many patients find the mould room visit distressing and so rapid prototyping could potentially improve the overall patient experience. Evaluation of a computer model of the immobilization system using an anthropomorphic phantom shows that >99% of vertices are within a tolerance of ±0.2 mm. Hausdorff distance was used to analyze CT slices obtained by rescanning the phantom with a printed mask in position. These results show that for >80% of the slices the median “worse-case” tolerance is approximately 4 mm. These measurements suggest that printed masks can achieve similar levels of immobilization to those of systems currently in clinical use

Automatic Removal of Mechanical Fixations from CT Imagery with Particle Swarm Optimisation

Fixation devices are used in radiotherapy treatment of head and neck cancers to ensure successive treatment fractions are accurately targeted. Typical fixations usually take the form of a custom made mask that is clamped to the treatment couch and these are evident in many CT data sets as radiotherapy treatment is normally planned with the mask in place. But the fixations can make planning more difficult for certain tumor sites and are often unwanted by third parties wishing to reuse the data. Manually editing the CT images to remove the fixations is time consuming and error prone. This paper presents a fast and automatic approach that removes artifacts due to fixations in CT images without affecting pixel values representing tissue. The algorithm uses particle swarm optimisation to speed up the execution time and presents results from five CT data sets that show it achieves an average specificity of 92.01% and sensitivity of 99.39%

Scholars’ Supreme Court Amicus Brief in Support of Neither Party: \u3cem\u3ePetrella v. Metro-Goldwyn-Mayer\u3c/em\u3e

The appeal to the Supreme Court in Petrella v. Metro-Goldwyn-Mayer deals with the equitable defense of plaintiff’s laches before suing for copyright infringement. Laches is unreasonable and prejudicial delay. MGM allegedly violated plaintiff’s copyright repeatedly over a period of many years; the statute of limitations has not run on the most recent violations. Plaintiff argues that laches should never apply to a cause of action with a statute of limitations. Defendant argues that laches should bar all relief if defendant relied on plaintiff’s failure to sue earlier, without having to match defendant’s reliance to the remedies plaintiff seeks. This scholars’ amicus brief, which supports neither party, argues against all-or-nothing solutions. In particular, the brief says that laches should be available as needed to protect defendant’s reliance, but that defendant should have to show how particular remedies would unfairly override particular reliance interests. Plaintiff also argues that laches should be unavailable because it would be a ground for refusing an injunction that was not mentioned in eBay v. MercExchange. The scholars’ brief takes this occasion to point out several unintended untoward consequences of the four-part test in eBay

A fast and automatic approach for removing artefacts due to immobilisation masks in X-ray CT

Immobilisation masks are fixation devices that are used when administering radiotherapy treatment to patients with tumours affecting the head and neck. Radiotherapy planning X-ray Computer Tomography (CT) data sets for these patients are captured with the immobilisation mask fitted and manually editing the X-ray CT images to remove artefacts due to the mask is time consuming and error prone. This paper represents the first study that employs a fast and automatic approach to remove image artefacts due to masks in X-ray CT images without affecting pixel values representing tissue. Our algorithm uses a fractional order Darwinian particle swarm optimisation of Otsu’s method combined with morphological post-processing to classify pixels belonging to the mask. The proposed approach is tested on five X-ray CT data sets and achieves an average specificity of 92.01% and sensitivity of 99.39%. We also present results demonstrating the comparative speed-up obtained by fractional order Darwinian particle swarm optimisation

Brief of Restitution and Remedies Scholars as Amici Curiae in Support of Respondent: \u3cem\u3eSpokeo v. Robins\u3c/em\u3e

Both consumer protection and restitution may be casualties in a collision with the constitutional law of standing. Spokeo collects information from the internet and publishes it; however, Spokeo neither verifies the facts nor confirms which same-named person it refers to. Robins alleges that Spokeo violated the Fair Credit Reporting Act by disseminating false information about him. He seeks class certification and up to $1,000 in statutory minimum damages instead of compensatory damages. Spokeo argues that Robins lacks standing because he suffered no “injury in fact,” no “concrete harm.” Statutory minimum recoveries for defendants’ violations of plaintiffs’ individual rights without proof of pecuniary damages or actual harm were well known before the American founding. Indeed the First Congress enacted at least one statutory minimum recovery. Congress continues to need the ability to legislate statutory minimum damages as remedies to protect consumers and other plaintiffs. This brief argues that the Court should not erode Congress’s efforts by denying standing to those plaintiffs. The search for harm beyond defendants’ violations of plaintiffs’ legally protected interests arose where defendants’ alleged public-law violations were not individualized, more generally where the laws at issue did not actually apply to plaintiffs. If, on the other hand, a defendant actually invades a plaintiff’s individualized statutory private-law “legally protected interest,” then that violation satisfies the standing prerequisite of “injury in fact.” The Court has never required a plaintiff to adduce an additional or consequential harm beyond a violation. This brief also warns the Court that accepting Spokeo’s standing argument will inadvertently lock the federal courthouse door to much of the law of restitution. Restitution is based on defendant’s gain, not plaintiff’s loss. Many restitution defendants made improper profits by violating plaintiffs’ legal rights without causing plaintiffs any pecuniary loss or harm. The brief reviews numerous long-standing restitution claims that do not involve any “injury in fact” under Spokeo’s apparent definition. These claims to recover a wrongdoer’s improper profits or to set aside a transaction tainted by a wrongdoer’s conflict of interest are crucial parts of our restitution jurisprudence. This brief calls on the Court to stand up for restitution

Building a house of C.A.R.D.S.: The practice structures of coaches in a professional rugby union academy

This chapter provides insights into the practice structures used by coaches of the Newcastle Falcons Rugby Union academy. It shows how training session activities are organised and adapted to purposefully develop creativity, awareness, resilience, decision-making and self-organisation (C.A.R.D.S.) among players aspiring to compete professionally. The chapter set out to create opportunities for every player in the Newcastle Falcons academy to explore the boundaries of their capabilities and adapt to the changing nature of the game of rugby union by developing C.A.R.D.S. skills. It draws on a range of concepts from dynamical systems theory, representative design, non-linear pedagogy, constraints-led coaching and games-based approaches. Making frequent amendments to the constraints of training activities is itself a form of adversity, as players need to remain aware and quickly adapt to respond to the new challenges posed. Self-organised players will have ‘the skill to use information to effectively coordinate themselves’

Earthworm uptake routes and rates of ionic Zn and ZnO nanoparticles at realistic concentrations, traced using stable isotope labeling

The environmental behavior of ZnO nanoparticles (NPs), their availability to, uptake pathways by, and biokinetics in the earthworm Lumbricus rubellus were investigated using stable isotope labeling. Zinc isotopically enriched to 99.5% in 68Zn (68Zn-E) was used to prepare 68ZnO NPs and a dissolved phase of 68Zn for comparison. These materials enabled tracing of environmentally relevant (below background) NP additions to soil of only 5 mg 68Zn-E kg–1. Uptake routes were isolated by introducing earthworms with sealed and unsealed mouthparts into test soils for up to 72 h. The Zn isotope compositions of the soils, pore waters and earthworms were then determined using multiple collector inductively coupled plasma mass spectrometry. Detection and quantification of 68Zn-E in earthworm tissue was possible after only 4 h of dermal exposure, when the uptake of 68Zn-E had increased the total Zn tissue concentration by 0.03‰. The results demonstrate that at these realistic exposure concentrations there is no distinguishable difference between the uptake of the two forms of Zn by the earthworm L. rubellus, with the dietary pathway accounting for ∼95% of total uptake. This stands in contrast to comparable studies where high dosing levels were used and dermal uptake is dominant

Novel multi-isotope tracer approach to test ZnO nanoparticle and soluble Zn bioavailability in joint soil exposures

Here we use two enriched stable isotopes, 68Znen and 64Znen (>99%), to prepare 68ZnO nanoparticles (NPs) and soluble 64ZnCl2. The standard LUFA 2.2 test soil was dosed with 68ZnO NPs and soluble 64ZnCl2 to 5 mg kg–1 each, plus between 0 and 95 mg kg–1 of soluble ZnCl2 with a natural isotope composition. After 0, 1, 3, 6, and 12 months of soil incubation, earthworms (Eisenia andrei) were introduced for 72 h exposures. Analyses of soils, pore waters, and earthworm tissues using multiple collector inductively coupled plasma mass spectrometry allowed the simultaneous measurement of the diagnostic 68Zn/66Zn, 64Zn/66Zn, and 68Zn/64Zn ratios, from which the three different isotopic forms of Zn were quantified. Eisenia andrei was able to regulate Zn body concentrations with no difference observed between the different total dosing concentrations. The accumulation of labeled Zn by the earthworms showed a direct relationship with the proportion of labeled to total Zn in the pore water, which increased with longer soil incubation times and decreasing soil pH. The 68Znen/64Znen ratios determined for earthworms (1.09 ± 0.04), soils (1.09 ± 0.02), and pore waters (1.08 ± 0.02) indicate indistinguishable environmental distribution and uptake of the Zn forms, most likely due to rapid dissolution of the ZnO NPs

Identification of binding residues between periplasmic adapter protein (PAP) and RND efflux pumps explains PAP-pump promiscuity and roles in antimicrobial resistance

Active efflux due to tripartite RND efflux pumps is an important mechanism of clinically relevant antibiotic resistance in Gram-negative bacteria. These pumps are also essential for Gram-negative pathogens to cause infection and form biofilms. They consist of an inner membrane RND transporter; a periplasmic adaptor protein (PAP), and an outer membrane channel. The role of PAPs in assembly, and the identities of specific residues involved in PAP-RND binding, remain poorly understood. Using recent high-resolution structures, four 3D sites involved in PAP-RND binding within each PAP protomer were defined that correspond to nine discrete linear binding sequences or "binding boxes" within the PAP sequence. In the important human pathogen Salmonella enterica, these binding boxes are conserved within phylogenetically-related PAPs, such as AcrA and AcrE, while differing considerably between divergent PAPs such as MdsA and MdtA, despite overall conservation of the PAP structure. By analysing these binding sequences we created a predictive model of PAP-RND interaction, which suggested the determinants that may allow promiscuity between certain PAPs, but discrimination of others. We corroborated these predictions using direct phenotypic data, confirming that only AcrA and AcrE, but not MdtA or MsdA, can function with the major RND pump AcrB. Furthermore, we provide functional validation of the involvement of the binding boxes by disruptive site-directed mutagenesis. These results directly link sequence conservation within identified PAP binding sites with functional data providing mechanistic explanation for assembly of clinically relevant RND-pumps and explain how Salmonella and other pathogens maintain a degree of redundancy in efflux mediated resistance. Overall, our study provides a novel understanding of the molecular determinants driving the RND-PAP recognition by bridging the available structural information with experimental functional validation thus providing the scientific community with a predictive model of pump-contacts that could be exploited in the future for the development of targeted therapeutics and efflux pump inhibitors