Paraxial diffusion-field retrieval

Unresolved spatially-random microstructure, in an illuminated sample, can lead to position-dependent blur when an image of that sample is taken using an incoherent imaging system. For a small propagation distance, between the exit surface of the sample and the entrance surface of a position-sensitive detector, the paraxial approximation implies that the blurring influence of the sample may be modeled using an anomalous-diffusion field. This diffusion field may have a scalar or tensor character, depending on whether the random microstructure has an autocorrelation function that is rotationally isotropic or anisotropic, respectively. Partial differential equations are written down and then solved, in a closed-form manner, for several variants of the inverse problem of diffusion-field retrieval given suitable intensity images. Both uniform-illumination and structured-illumination schemes are considered. Links are made, between the recovered diffusion field and certain statistical properties of the unresolved microstructure. The developed theory -- which may be viewed as a crudely parallel form of small-angle scattering under the Guinier approximation -- is applicable to a range of paraxial radiation and matter fields, such as visible light, x rays, neutrons, and electrons

Directional dark field retrieval with single-grid x-ray imaging

Directional dark-field imaging is an emerging x-ray modality that is sensitive to unresolved anisotropic scattering from sub-pixel sample microstructures. A single-grid imaging set-up can be used to capture dark-field images by looking at changes in a grid pattern projected upon the sample. By creating analytical models for the experiment, we have developed a single-grid directional dark field retrieval algorithm that can extract dark-field parameters such as the dominant scattering direction, and the semi-major and -minor scattering angles. We show that this method is effective even in the presence of high image noise, allowing for low dose and time sequence imaging

A fast implicit X-ray diffusive-dark-field retrieval method using a single mask and exposure

Complementary to conventional and phase X-ray radiography, dark-field imaging has become central in visualizing diffusive scattering signal due to the spatially-unresolved texture within an object. To date most diffusive-dark-field retrieval methods require either the acquisition of multiple images at the cost of higher radiation dose or significant amounts of computational memory and time. In this work, a simple method of X-ray diffusive dark-field retrieval is presented, applicable to any single-mask imaging setup, with only one exposure of the sample. The approach, which is based on a model of geometric and diffusive reverse-flow conservation, is implicit and non-iterative. This numerically fast methodology is applied to experimental X-ray images acquired using both a random mask and a grid mask, giving high quality reconstructions that are very stable in the presence of noise. The method should be useful for high-speed imaging and/or imaging with low-flux sources

Multimodal Intrinsic Speckle-Tracking (MIST) to extract rapidly-varying diffuse X-ray scatter

Speckle-based phase-contrast X-ray imaging (SB-PCXI) can reconstruct high-resolution images of weakly-attenuating materials that would otherwise be indistinguishable in conventional attenuation-based imaging. The experimental setup of SB-PCXI requires only a sufficiently coherent source and spatially random mask, positioned between the source and detector. The technique can extract sample information at length scales smaller than the imaging system's spatial resolution; this enables multimodal signal reconstruction. ``Multimodal Intrinsic Speckle-Tracking'' (MIST) is a rapid and deterministic formalism derived from the paraxial-optics form of the Fokker-Planck equation. MIST simultaneously extracts attenuation, refraction, and small-angle scattering (diffusive-dark-field) signals from a sample and is more computationally efficient compared to alternative speckle-tracking approaches. Hitherto, variants of MIST have assumed the diffusive-dark-field signal to be spatially slowly varying. Although successful, these approaches have been unable to well-describe unresolved sample microstructure whose statistical form is not spatially slowly varying. Here, we extend the MIST formalism such that there is no such restriction, in terms of a sample's rotationally-isotropic diffusive-dark-field signal. We reconstruct multimodal signals of two samples, each with distinct X-ray attenuation and scattering properties. The reconstructed diffusive-dark-field signals have superior image quality compared to our previous approaches which assume the diffusive-dark-field to be a slowly varying function of transverse position. Our generalisation may assist increased adoption of SB-PCXI in applications such as engineering and biomedical disciplines, forestry, and palaeontology, and is anticipated to aid the development of speckle-based diffusive-dark-field tensor tomography.Comment: 18 pages, 7 figure

Increasing the accessibility and impact of justice-related student and practitioner research

Much good quality research by pre-doctoral students and case-work focused practitioners remains unpublished. However, their findings could contribute to the evidence base underpinning science and practice within international justice system contexts. There are two main challenges to making findings accessible: reaching all criminal justice stakeholders, and encouraging collaborative efforts in research addressing ‘real world’ problems. This article presents the rationale for a new, open access repository. The aim is to share good quality pre-doctoral and practitioner criminal justice research across traditional disciplinary and international borders. Such a repository should be easy to use, well maintained and sustainable. Its reach, value and impact also need to be measurable. We present the major considerations relating to the operation and workflow of such a repository, and outline the potential value, benefits and limitations. Our research suggests that the proposed repository could foster interdisciplinary and collaborative work to benefit global justice systems and societies

Brexanolone, a GABAA Modulator, in the Treatment of Postpartum Depression in Adults: A Comprehensive Review

Postpartum depression (PPD) is one of the three major categories on the spectrum of postpartum psychiatric syndromes. Postpartum psychiatric syndromes are classified as either postpartum blues, postpartum depression, or postpartum psychosis. Postpartum depression is important to recognize clinically because of the effect it can have on the mother-child bond. The neurosteroid allopregnanolone, a progesterone derivative, is important for its role in positively modulating GABAA receptors. GABA-mediated signaling has been previously implicated in major depressive disorder. Allopregnanolone-mediated signaling has been identified as an important therapeutic target. Treatment with an allopregnanolone-analog, brexanolone, has been shown to improve depression scores in trials for the treatment of PPD. Brexanolone is a positive allosteric modulator of GABAA and is the first drug approved by the FDA to treat postpartum depression. Brexanolone enhances the inhibitory effects of GABAA, restores dysfunctional GABAA transmembrane channels, and mimics a naturally produced progesterone metabolite that fluctuates during pregnancy and postpartum. One open-label study and two phase two studies have some significant reduction in HAM-D scores after treatment and that the effect was still there 30 days post-treatment. Per the data reported, intravenous infusion of brexanolone could be efficacious and safe for the treatment of women suffering from postpartum depression

Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare salivary cancer. The highest rates of disease recurrence are in patients with NOTCH pathway activation, reported in up to 20%. Novel drugs targeting NOTCH signaling are under investigation in the recurrent/metastatic (R/M) setting. To understand their clinical utility, there is an urgent need to better characterize the disease course and outcomes following current standard of care treatment. METHODS: 120 patients with R/M ACC underwent clinical review at a single UK Cancer Centre. Patients were retrospectively assessed for tumor NOTCH pathway activation using next generation sequencing (NGS) targeting NOTCH1/2/3 genes and/or NOTCH1 intra-cellular domain (NICD1) immunohistochemistry. Demographic and treatment data were extracted from the clinical notes. Kaplan-Meier survival analysis was performed using log rank test. RESULTS: NOTCH pathway activation was identified in 13/120 patients (11 %). In 12/101 patients analyzed by NGS, NOTCH1/3 activating somatic mutations were identified, and a further patient was identified with NICD1 diffuse nuclear staining in whom NGS testing was not possible. Patients with NOTCH pathway activation had shorter median RFS (1.1 vs 3.4 years, p = 0.2032) and significantly reduced median OS from diagnosis (4.0 vs 16.3 years, p < 0.0001). There was significantly reduced median OS from time of disease recurrence/metastasis (1.9 vs 9.6 years, p < 0.0001). CONCLUSION: This study clearly demonstrates a reduction in OS from time of first confirmed disease recurrence/metastasis for patients with NOTCH pathway activated ACC. This provides support for developing new drugs for this sub-group of patients, for whom clinical outcomes are significantly worse and effective treatments are lacking