Cooperative Jahn-Teller Distortion in PrO2

We report neutron diffraction data on single crystal PrO2 which reveal a cooperative Jahn-Teller distortion at TD = 120 +/- 2 K. Below this temperature an internal distortion of the oxygen sublattice causes the unit cell of the crystallographic structure to become doubled along one crystal axis. We discuss several possible models for this structure. The antiferromagnetic structure below TN = 13.5 K is found to consist of two components, one of which shares the same doubled unit cell as the distorted crystallographic structure. We also present measurements of the magnetic susceptibility, the specific heat capacity and the electrical conductivity of PrO2. The susceptibility data show an anomaly at a temperature close to TD. From the specific heat capacity data we deduce that the ground state is doubly degenerate, consistent with a distortion of the cubic local symmetry. We discuss possible mechanisms for this. The conductivity shows an activated behaviour with an activation energy Ea = 0.262 +/- 0.003 eV.Comment: 12 pages, 14 figures, 2 tables. Additional suggested structure in v

Aesthetic experience and spiritual well-being: locating the role of theological commitments

I discuss three accounts of the spiritual significance of aesthetic experience. Two of these perspectives I have taken from the recent literature in theological aesthetics, and the third I have constructed, building on Thomas Aquinas’s conception of the goods of the infused moral virtues. This broadly Thomistic approach occupies, I argue, a middle ground between the other two, on account of its distinctive understanding of the role of theological context in defining spiritually significant goods. These perspectives are not mutually exclusive, but they do present rather different conceptions of the ways in which aesthetic goods can contribute to spiritual well-being, and provide a focus for religious practice

Exploring obstacles to critical care trials in the UK: A qualitative investigation

BACKGROUND: Clinical trials in critical care are often resource-intense, with many unique challenges. Barriers to effective recruitment and implementation of study intervention have not been explored in a UK context. AIM: To identify facilitating factors and barriers to enrolling patients into critical care clinical trials within the UK from clinician's perspectives. METHODS: A qualitative interview study was undertaken on behalf of the National Institute of Health Research critical care specialty group, in which research active clinicians across different Clinical Research Networks were interviewed. A loosely structured interview schedule was used, based on themes generated from the literature associated with accessing critical care trials. Research teams (critical care doctors, research nurses, and trial coordinators) from hospitals from each Clinical Research Network were contacted to try to achieve representation across the UK. RESULTS: Interviews were carried out across nine UK Clinical Research Networks with a range of doctors and research nurses. All hospitals were teaching hospitals with varying research nurse numbers and allocated consultant research sessions. There were a range of six to nine ongoing clinical trials in critical care for each centre representative interviewed. Data were analysed using framework analysis, and six final themes were identified related to factors associated with: centre, unit, resources, study, clinician, and patient/family. The most commonly cited barrier to conducting clinical trials was related to resources, namely insufficient human and financial resources, leading to staff and study recruitment difficulties. Clinical uncertainty and equipoise regarding comparative merits of trials were challenging in terms of engaging critical care teams. A number of patient and family factors added complexities in terms of recruitment; however, refusal rates were generally reported as low. CONCLUSION: Flexibility in funding and employment by research teams enables continuity of studies and staff. Innovative measures to incentivise research nurses and clinical teams can help recruit more patients into trials. Research teams are highly committed to providing cover to recruit critical care trials, and a significant effort to anticipate barriers is undertaken; these endeavours are summarised to provide guidance for other teams wishing to address any potential difficulties

A two-circle powder diffractometer for synchrotron radiation on Station 2.3 at the SRS

The two-circle powder diffractometer on Station 8.3 at the SRS has recently been relocated to station 2.3, some half the distance from a dipole radiation source with the same nominal 1.2T field. The purpose of this paper is to detail the changes and modifications to the diffractometer operation

An immunotherapy survivor population: health-related quality of life and toxicity in patients with metastatic melanoma treated with immune checkpoint inhibitors

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Purpose The immune checkpoint inhibitors (ICIs) have resulted in subgroups of patients with metastatic melanoma achievinghigh-quality durable responses. Metastatic melanoma survivors are a new population in the era of cancer survivorship. The aimofthis study was to evaluate metastatic melanoma survivors in terms of health-related quality of life (HRQoL), immune-relatedadverse events (irAEs) and exposure to immunosuppressive agents in a large single centre in the UK.Methods We defined the survivor population as patients with a diagnosis of metastatic melanoma who achieved a durableresponse to an ICI and had been followed-up for a minimum of 12 months from initiation of ICI without disease progression.HRQoL was assessed using SF-36. Electronic health records were accessed to collect data on demographics, treatments, irAEsand survival. HRQoL data was compared with two norm-based datasets.Results Eighty-four metastatic melanoma survivors were eligible and 87% (N = 73) completed the SF-36. ICI-related toxicity ofany grade occurred in 92%of patients and 43%had experienced a grade 3 or 4 toxicity. Almost half (49%) of the patients requiredsteroids for the treatment of ICI-related toxicity, whilst 14% required treatment with an immunosuppressive agent beyondsteroids.Melanoma survivors had statistically significant lower HRQoL scores with regard to physical, social and physical rolefunctioning and general health compared with the normative population. There was a trend towards inferior scores in patientswith previous exposure to ipilimumab compared with those never exposed to ipilimumab.Conclusions Our results show that metastatic melanoma survivors have potentially experienced significant ICI-related toxicityand experience significant impairments in specific HRQoL domains. Future service planning is required to meet this population’sunique survivorship needs.Peer reviewe

Increasing Soil Suppressivity to Fusarium Wilt of Banana Through Banana Intercropping with Allium Spp.

Fusarium wilt, caused by Fusarium oxysporum f.sp. cubense (Foc), is one of the most destructive diseases of banana and has spread in many plantation areas in Indonesia. Until today, the effective ways to control banana fusarium wilt disease have not yet been found. Some studies indicated thatAllium spp. could be used to suppress plant diseases caused by Fusarium. Allium spp. are important horticultural crops which are generally cultivated in some areas in Indonesia. This research was conducted to determine the effect of several species ofAllium spp. intercropped with banana to improve soil suppressiveness against banana fusarium wilt disease. The results showed that up to 12 months after planting, from 3 species ofAllium spp. (A. tuberosum/ Chinese leek, A. fistulosum/ bunching onion, and A. cepa var. aggregatum/ shallot) intercropped with banana Ambon Kuning (AAA) cultivar, Chinese leek and shallot were able to suppress the incidence of fusarium wilt disease of banana by 46 and 33% respectively. Soil analysis on the rhizosphere of banana intercropped with Chinese leek and shallot had lower population of total Fusarium compared to the other treatments. Analysis of fluorescein diacetate (3'.6'-diacetylfluoerescein) or FDA also showed that total microbial activity in the rhizosphere of banana intercropped withAllium spp. was also lower compared to control treatment (without intercropping). The observation of the effect ofAllium spp. extracts on Foc showed that Allium spp. extracts were able to suppress the development of the colony and spore germination of Foc in vitro. INTISARILayu Fusarium, yang disebabkan oleh Fusarium oxysporum f.sp. cubense (Foc), merupakan salah satu penyakit tanaman pisang yang paling merusak dan telah tersebar di berbagai daerah di Indonesia. Sampai saat ini cara yang efektif untuk mengendalikan penyakit layu fusarium pisang belum ditemukan. Beberapa penelitian menunjukkan bahwa Allium spp. dapat dipergunakan untuk menekan penyakit tumbuhan yang disebabkan oleh Fusarium. Allium spp. adalah tanaman hortikultura penting yang banyak dibudidayakan di Indonesia. Penelitian ini dilakukan untuk mengetahui pengaruh beberapa spesiesAllium spp. yang ditumpangsarikan dengan tanaman pisang untuk meningkatkan supresifitas tanah dalam menekan penyakit layu fusarium pisang. Hasil pengamatan menunjukkan bahwa sampai 12 bulan setelah tanam, dari 3 spesiesAllium spp. (A. tuberosum/kucai, A. fistulosum/loncang, dan A. cepa var. aggregatum/bawang merah) yang ditumpangsarikan dengan pisang kultivar Ambon Kuning (AAA), kucai dan bawang merah mampu menekan insidensi penyakit layu fusarium pisang berturut-turut sebesar 46% dan 33%. Analisis tanah rhizosfer pisang yang ditumpang sari dengan kucai dan bawang merah menunjukkan populasi total Fusarium yang lebih rendah daripada perlakuan lainnya. Analisis fluorescein diacetate (3'.6'-diacetylfluoerescein) atau FDA juga menunjukkan bahwa aktivitas total mikrobia pada rhizosfer pisang yang ditumpang sari dengan Allium spp. lebih rendah jika dibandingkan dengan perlakuan kontrol (tanpa tumpang sari). Pengamatan pengaruh ekstrak Allium spp. terhadap Foc menunjukkan bahwa ekstrak Allium spp. mampu menekan perkembangan koloni dan perkecambahan spora Foc secara in vitro

Innovations in Simulation: Experiences with Cloud-based Simulation Experimentation

The amount of simulation experimentation that can be performed in a project can be restricted by time, especially if a model takes a long time to simulate and many replications are required. Cloud Computing presents an attractive proposition to speeding up, or extending, simulation experimentation as computing resources can be hired on demand rather than having to invest in costly infrastructure. However, it is not common practice for simulation users to take advantage of this and, arguably, rather than speeding up simulation experimentation users tend to make compromises by using unnecessary model simplification techniques. This may be due to a lack of awareness of what Cloud Computing can offer. Based on several years’ experience of innovation in this area, this article presents our experiences in developing Cloud Computing applications for simulation experimentation and discusses what future innovations might be created for the widespread benefit of our simulation community

A viscoelastic – viscoplastic material model for superalloy applications

An understanding of rate dependency over a wide range of time scales is vitally important in approximating the transient response of critical components operating in extreme environments. Many examples of viscoplastic model formulations can be found in the literature, wherein all rate dependency is assumed to occur after yielding. Such models neglect any viscous effects during elastic deformation. In the present work, a unified viscoelastic – viscoplastic material model is developed for the Nickel superalloy RR1000. Particular emphasis is placed on model parameter determination, which is accomplished using standard cyclic plasticity and stress relaxation experimental data

Industry Simulation Gateway on a Scalable Cloud

Large scale simulation experimentation typically requires significant computational resources due to an excessive number of simulation runs and replications to be performed. The traditional approach to provide such computational power, both in academic research and industry/business applications, was to use computing clusters or desktop grid resources. However, such resources not only require upfront capital investment but also lack the flexibility and scalability that is required to serve a variable number of clients/users efficiently. This paper presents how SakerGrid, a commercial desktop grid based simulation platform and its associated science gateway have been extended towards a scalable cloud computing solution. The integration of SakerGrid with the MiCADO automated deployment and autoscaling framework supports the execution of multiple simulation experiments by dynamically allocating virtual machines in the cloud in order to complete the experiment by a user-defined deadline

Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model

BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. METHODOLOGY/PRINCIPLE FINDINGS: EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). CONCLUSIONS/SIGNIFICANCE: Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells for effective treatment of human patients with recurrent glioblastoma