Incipient empyema as an embolic complication of group A streptococcal septic arthritis in a patient with concomitant influenza B infection.

A 43-year-old healthy male presented with left ankle septic arthritis. Surgical specimens cultured Streptococcus pyogenes (group A Streptococcus, GAS) and IV benzylpenicillin was commenced. In the setting of coryzal symptoms, a chest radiograph and nasopharyngeal swab revealed a left-sided pleural effusion and influenza B infection, respectively. Persisting fevers, rising CRP, and increasing breathlessness led to repeat chest radiography showing a rapidly enlarging left-sided effusion. Following intercostal catheter insertion with intrapleural fibrinolytic therapy, 6 L of haemorrhagic fluid was drained leading to defervescence and clinical improvement. At follow-up 4 weeks later, he was asymptomatic with a normal chest radiograph. Similar to previous reported cases of GAS empyema, this case was associated with concurrent viral respiratory tract infection, but is unusual as it arose through haematogenous seeding from an extra-thoracic source. This case reminds clinicians to be aware of the strongly pyogenic nature of GAS and its significance as a potential cause of pleural infection, especially in patients with concomitant viral respiratory infections

Modelling of compressional alfvén eigencmodes in axisymmetric toroidal fusion plasmas

Compressional Alfven eigenmodes (CAEs) have been linked to electromagnetic emission detected in tokamaks in the frequency range around harmonics of the ion cyclotron frequency, and more recently to sub-ion cyclotron frequency emission in spherical tokamak experiments. This has sparked interest in using CAEs as a diagnostic for fast-ion distributions in fusion devices. This thesis presents a linear stability code, Whales2, that solves for CAEs using the linearised cold ideal Hall- MHD equations. Whales2 is a mixed finite elements spectral code that operates in a 2-dimensional axisymmetric toroidal geometry to solve for the frequency and spatial structure of CAEs in a given ideal-MHD equilibrium. In this thesis we present how the Whales2 code is designed to calculate CAEs whilst avoiding the physical coupling of CAEs to the slow-magnetoacoustic and shear Alfven eigenmodes. We demonstrate that Whales2 is free from spectral pollution and that the self-adjointness of the ideal-MHD equations is preserved in the numerical methods employed by Whales2. We show that Whales2 well reproduces analytical and qualitative predictions of CAE theory in a range of test cases in cylindrical and toroidal geometries. We also use output from Whales2 to establish the behaviour of CAEs with respect to including the Hall term in the MHD equations, particularly in the lifting of the positive/negative frequency degeneracy that is present in ideal-MHD. Results from Whales2 show the impact that the Hall term can have on the spatial localisation of CAEs. Whales2 manipulates the MHD equations based on the method detailed in [3] to avoid CAE coupling to the shear Alfven continuum - the effectiveness of this method is demonstrated clearly for the first time, to the author's knowledge. x

CHARACTERISATION OF HYDRIDE PRECIPITATION AND REORIENTATION IN ZIRCALOY-4 AT DIFFERENT METALLURGICAL STATES

Hydride precipitation and reorientation has the potential to embrittle zirconium alloys. This study aims to better understand the influence of the Zr microstructure on hydride precipitation and reorientation. Specifically, the crystallography, phase stability and morphology of hydride precipitation was correlated to microstructural variations due to changes in the metallurgical state of the zirconium alloy. The work highlights, that microstructural features induced during recrystallisation have a significant influence on the distribution and orientation of hydrides when no external stress is applied. The stability of ϒ-hydride was shown to be dictated by metallurgical state whereby its formation was promoted in the recrystallised sample owing to its reduced strength. The influence of grain orientation on ϒ stability was also explored. It was highlighted that upon cooling, grains oriented in the <101 ̅0> direction are under compression such that ϒ-hydride formation is supressed. This study suggests that the extent of reorientation is driven by differences in hydrogen content of the alloy as well as the applied stress during reorientation, whilst the influence of the metallurgical state still remains unclear. Quantification of the dislocation density in both the matrix and hydride during precipitation highlighted that extensive matrix recovery takes place during hydriding. It was also shown that the dislocation density in the hydride is lower after thermomechanical loading whereby the presence of dislocation nests left behind after initial hydride precipitation and dissolution could provide more space for the hydride to precipitate into

Yield of colorectal cancer at colonoscopy according to faecal haemoglobin concentration in symptomatic patients referred from primary care

Background: Lower gastrointestinal (GI) symptoms are poor predictors of colorectal cancer (CRC). This study examined the diagnostic yield of colonoscopy by faecal haemoglobin concentration (f‐Hb) in symptomatic patients assessed in primary care by faecal immunochemical testing (FIT). Methods: In three Scottish NHS Boards, FIT kits (HM‐JACKarc, Hitachi Chemical Diagnostics Systems Co., Ltd, Tokyo, Japan) were used by GPs to guide referrals for patients with lower GI symptoms (lab data studied for 12 months from December 2015 onward in Tayside, 18 months from June 2018 onward in Fife, and 5 months from September 2018 onward in Greater Glasgow and Clyde). CRC cases diagnosed at colonoscopy were ascertained from colonoscopy and pathology records. Results: 4841 symptomatic patients who underwent colonoscopy after FIT submission were included. Of 2166 patients (44.7%) with f‐Hb <10 µg Hb/g faeces (µg/g), 14 (0.6%) were diagnosed with CRC, with a number needed to scope (NNS) of 155. Of 2675 patients (55.3%) with f‐Hb ≥10 µg/g, 252 were diagnosed with CRC (9.4%) with a NNS of 11. Of 705 patients with f‐Hb ≥400 µg/g, 158 (22.4%) were diagnosed with CRC with a NNS of 5. Over half of those diagnosed with CRC with f‐Hb <10 µg/g had co‐existing anaemia. Conclusions: Symptomatic patients with f‐Hb ≥10 µg/g should undergo further investigation for CRC, while higher f‐Hb could be used to triage its urgency during the COVID‐19 recovery phase. Patients with f‐Hb <10 µg/g, without anaemia, are very unlikely to be diagnosed with CRC and the majority need no further investigation

Water-Soluble Truncated Fatty Acid-Porphyrin Conjugates Provide Photo-Sensitizer Activity for Photodynamic Therapy in Malignant Mesothelioma.

Clinical trials evaluating intrapleural photodynamic therapy (PDT) are ongoing for mesothelioma. Several issues still hinder the development of PDT, such as those related to the inherent properties of photosensitizers. Herein, we report the synthesis, photophysical, and photobiological properties of three porphyrin-based photosensitizers conjugated to truncated fatty acids (C5SHU to C7SHU). Our photosensitizers exhibited excellent water solubility and high PDT efficiency in mesothelioma. As expected, absorption spectroscopy confirmed an increased aggregation as a consequence of extending the fatty acid chain length. In vitro PDT activity was studied using human mesothelioma cell lines (biphasic MSTO-211H cells and epithelioid NCI-H28 cells) alongside a non-malignant mesothelial cell line (MET-5A). The PDT effect of these photosensitizers was initially assessed using the colorimetric WST-8 cell viability assay and the mode of cell death was determined via flow cytometry of Annexin V-FITC/PI-stained cells. Photosensitizers appeared to selectively localize within the non-nuclear compartments of cells before exhibiting high phototoxicity. Both apoptosis and necrosis were induced at 24 and 48 h. As our pentanoic acid-derivatized porphyrin (C5SHU) induced the largest anti-tumor effect in this study, we put this forward as an anti-tumor drug candidate in PDT and photo-imaging diagnosis in mesothelioma

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals