"I am not delusional!" Sensory dysaesthesia secondary to degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction, most classically presenting with a broad-based gait and clumsy hands. Limb sensory loss and paraesthesia are considered common symptoms of DCM. However, we report an unusual case of a patient presenting with prominent and atypical sensory symptoms. The patient repeatedly presented to accident and emergency complaining of her body resembling a wet gel-like substance that she attributed to the use of olive oil moisturising cream. The patient was found to have myelopathic signs on examination and MRI consistent with severe cervical myelopathy. She subsequently underwent successful decompressive anterior cervical discectomy, as recommended by international guidelines. This case serves to remind health professionals of uncommon presentations of common disease and the importance of maintaining a wide initial differential diagnosis

Multi-shot Echo Planar Imaging for accelerated Cartesian MR Fingerprinting: An alternative to conventional spiral MR Fingerprinting.

PURPOSE: To develop an accelerated Cartesian MRF implementation using a multi-shot EPI sequence for rapid simultaneous quantification of T1 and T2 parameters. METHODS: The proposed Cartesian MRF method involved the acquisition of highly subsampled MR images using a 16-shot EPI readout. A linearly varying flip angle train was used for rapid, simultaneous T1 and T2 quantification. The results were compared to a conventional spiral MRF implementation. The acquisition time per slice was 8s and this method was validated on two different phantoms and three healthy volunteer brains in vivo. RESULTS: Joint T1 and T2 estimations using the 16-shot EPI readout are in good agreement with the spiral implementation using the same acquisition parameters (<4% deviation for T1 and <6% deviation for T2). The T1 and T2 values also agree with the conventional values previously reported in the literature. The visual qualities of fine brain structures in the multi-parametric maps generated by multi-shot EPI-MRF and Spiral-MRF implementations were comparable. CONCLUSION: The multi-shot EPI-MRF method generated accurate quantitative multi-parametric maps similar to conventional Spiral-MRF. This multi-shot approach achieved considerable k-space subsampling and comparatively short TRs in a similar manner to spirals and therefore provides an alternative for performing MRF using an accelerated Cartesian readout; thereby increasing the potential usability of MRF.The research leading to these results has received funding from the European Commission H2020 Framework Programme (H2020- MSCAITN- 2014), number 642685 MacSeNet, the Engineering and Physical Sciences Research Council (EPSRC) platform Compressed Quantitative MRI grant, number EP/M019802/1 and the Scottish Research Partnership in Engineering (SRPe) award, number SRPe PECRE1718/ 17

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects

Giant molecular filaments in the Milky Way II. The fourth Galactic quadrant

Context: Filamentary structures are common morphological features of the cold, molecular interstellar medium (ISM). Recent studies have discovered massive, hundred-parsec-scale filaments that may be connected to the large-scale, Galactic spiral arm structure. Addressing the nature of these giant molecular filaments (GMFs) requires a census of their occurrence and properties. Aims: We perform a systematic search of GMFs in the fourth Galactic quadrant and determine their basic physical properties. Methods: We identify GMFs based on their dust extinction signatures in the near- and mid-infrared and the velocity structure probed by 13CO line emission. We use the 13CO line emission and ATLASGAL dust emission data to estimate the total and dense gas masses of the GMFs. We combine our sample with an earlier sample from literature and study the Galactic environment of the GMFs. Results: We identify nine GMFs in the fourth Galactic quadrant: six in the Centaurus spiral arm and three in inter-arm regions. Combining this sample with an earlier study using the same identification criteria in the first Galactic quadrant results in 16 GMFs, nine of which are located within spiral arms. The GMFs have sizes of 80–160 pc and 13CO-derived masses between 5−90 × 104M⊙. Their dense gas mass fractions are between 1.5–37%, which is higher in the GMFs connected to spiral arms. We also compare the different GMF-identification methods and find that emission and extinction-based techniques overlap only partially, thereby highlighting the need to use both to achieve a complete census

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states