Multiscale correlative tomography: an investigation of creep cavitation in 316 stainless steel

Creep cavitation in an ex-service nuclear steam header Type 316 stainless steel sample is investigated through a multiscale tomography workflow spanning eight orders of magnitude, combining X-ray computed tomography (CT), plasma focused ion beam (FIB) scanning electron microscope (SEM) imaging and scanning transmission electron microscope (STEM) tomography. Guided by microscale X-ray CT, nanoscale X-ray CT is used to investigate the size and morphology of cavities at a triple point of grain boundaries. In order to understand the factors affecting the extent of cavitation, the orientation and crystallographic misorientation of each boundary is characterised using electron backscatter diffraction (EBSD). Additionally, in order to better understand boundary phase growth, the chemistry of a single boundary and its associated secondary phase precipitates is probed through STEM energy dispersive X-ray (EDX) tomography. The difference in cavitation of the three grain boundaries investigated suggests that the orientation of grain boundaries with respect to the direction of principal stress is important in the promotion of cavity formation

3D Characterisation of Dry Powder Inhaler Formulations: Developing X-ray Micro Computed Tomography Approaches.

Carrier-based dry powder inhaler (DPI) formulations need to be accurately characterised for their particle size distributions, surface roughnesses, fines contents and flow properties. Understanding the micro-structure of the powder formulation is crucial, yet current characterisation methods give incomplete information. Commonly used techniques like laser diffraction (LD) and optical microscopy (OM) are limited due to the assumption of sphericity and can give variable results depending on particle orientation and dispersion. The aim of this work was to develop new powder analytical techniques using X-ray computed tomography (XCT) that could be employed for non-destructive metrology of inhaled formulations. α-lactose monohydrate powders with different characteristics have been analysed, and their size and shape (sphericity/aspect ratio) distributions compared with results from LD and OM. The three techniques were shown to produce comparable size distributions, while the different shape distributions from XCT and OM highlight the difference between 2D and 3D imaging. The effect of micro-structure on flowability was also analysed through 3D measurements of void volume and tap density. This study has demonstrated for the first time that XCT provides an invaluable, non-destructive and analytical approach to obtain number- and volume-based particle size distributions of DPI formulations in 3D space, and for unique 3D characterisation of powder micro-structure

Multi-Dimensional Characterization of Battery Materials

Demand for low carbon energy storage has highlighted the importance of imaging techniques for the characterization of electrode microstructures to determine key parameters associated with battery manufacture, operation, degradation, and failure both for next generation lithium and other novel battery systems. Here, recent progress and literature highlights from magnetic resonance, neutron, X-ray, focused ion beam, scanning and transmission electron microscopy are summarized. Two major trends are identified: First, the use of multi-modal microscopy in a correlative fashion, providing contrast modes spanning length- and time-scales, and second, the application of machine learning to guide data collection and analysis, recognizing the role of these tools in evaluating large data streams from increasingly sophisticated imaging experiments

The Obligation of Physicians to Medical Outliers: A Kantian and Hegelian Synthesis

Background Patients who present to medical practices without health insurance or with serious co-morbidities can become fiscal disasters to those who care for them. Their consumption of scarce resources has caused consternation among providers and institutions, especially as it concerns the amount and type of care they should receive. In fact, some providers may try to avoid caring for them altogether, or at least try to limit their institutional or practice exposure to them. Discussion We present a philosophical discourse, with emphasis on the writings of Immanuel Kant and G.F.W. Hegel, as to why physicians have the moral imperative to give such outliers considerate and thoughtful care. Outliers are defined and the ideals of morality, responsibility, good will, duty, and principle are applied to the care of patients whose financial means are meager and to those whose care is physiologically futile. Actions of moral worth, unconditional good will, and doing what is right are examined. Summary Outliers are a legitimate economic concern to individual practitioners and institutions, however this should not lead to an evasion of care. These patients should be identified early in their course of care, but such identification should be preceded by a well-planned recognition of this burden and appropriate staffing and funding should be secured. A thoughtful team approach by medical practices and their institutions, involving both clinicians and non-clinicians, should be pursued

Crystallographic Tomography and Molecular Modelling of Structured Organic Polycrystalline Powders

A fundamental understanding of the behaviour of polycrystalline materials, including pharmaceuticals, is vital for control of their physicochemical and crystalline properties, which in turn has the potential to improve drug product development for example. In this work, attenuation X-ray computed tomography (CT) and diffraction contrast tomography (DCT) are combined with molecular modelling to understand the powder packing behaviour and crystal interactions of the organic cubic compound hexamine (hexamethylenetetramine). It is the first application of DCT to polycrystalline organic materials. The crystal morphology is predicted through synthonic modelling, with fully 3D-resolved confirmation of the crystallography of the external {110} facets, edges and corner directions by DCT. Analysis of the powder-bed reveals agglomerate structures and orientational texture, with its chemical origins energetically predicted to be face-to-face in accordance with the experimental data. Finally, measurements of crystal & crystallite interactions provide evidence for different mechanisms of powder bed agglomeration

Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice

Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations, often leading to uninterpretable or invalid outcomes. If the statistical concepts identified within this review are considered and addressed during the design of a trial amendment, it is possible to effectively assess a new treatment arm within an ongoing trial without compromising the original trial outcomes

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

Search for gamma-ray emission from magnetars with the Fermi Large Area Telescope

We report on the search for 0.1-10 GeV emission from magnetars in 17 months of Fermi Large Area Telescope (LAT) observations. No significant evidence for gamma-ray emission from any of the currently-known magnetars is found. The most stringent upper limits to date on their persistent emission in the Fermi-LAT energy range are estimated between ~10^{-12}-10^{-10} erg/s/cm2, depending on the source. We also searched for gamma-ray pulsations and possible outbursts, also with no significant detection. The upper limits derived support the presence of a cut-off at an energy below a few MeV in the persistent emission of magnetars. They also show the likely need for a revision of current models of outer gap emission from strongly magnetized pulsars, which, in some realizations, predict detectable GeV emission from magnetars at flux levels exceeding the upper limits identified here using the Fermi-LAT observations.Comment: ApJ Letters in press; Corresponding authors: Caliandro G. A., Hadasch D., Rea N., Burnett

Detection of Gamma-Ray Emission from the Starburst Galaxies M82 and NGC 253 with the Large Area Telescope on Fermi

We report the detection of high-energy gamma-ray emission from two starburst galaxies using data obtained with the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. Steady point-like emission above 200 MeV has been detected at significance levels of 6.8 sigma and 4.8 sigma respectively, from sources positionally coincident with locations of the starburst galaxies M82 and NGC 253. The total fluxes of the sources are consistent with gamma-ray emission originating from the interaction of cosmic rays with local interstellar gas and radiation fields and constitute evidence for a link between massive star formation and gamma-ray emission in star-forming galaxies.Comment: Submitted to ApJ Letter