Exploring contrast generalisation in deep learning-based brain MRI-to-CT synthesis

BACKGROUND: Synthetic computed tomography (sCT) has been proposed and increasingly clinically adopted to enable magnetic resonance imaging (MRI)-based radiotherapy. Deep learning (DL) has recently demonstrated the ability to generate accurate sCT from fixed MRI acquisitions. However, MRI protocols may change over time or differ between centres resulting in low-quality sCT due to poor model generalisation. PURPOSE: investigating domain randomisation (DR) to increase the generalisation of a DL model for brain sCT generation. METHODS: CT and corresponding T 1-weighted MRI with/without contrast, T 2-weighted, and FLAIR MRI from 95 patients undergoing RT were collected, considering FLAIR the unseen sequence where to investigate generalisation. A "Baseline" generative adversarial network was trained with/without the FLAIR sequence to test how a model performs without DR. Image similarity and accuracy of sCT-based dose plans were assessed against CT to select the best-performing DR approach against the Baseline. RESULTS: The Baseline model had the poorest performance on FLAIR, with mean absolute error (MAE) = 106 ± 20.7 HU (mean ±σ). Performance on FLAIR significantly improved for the DR model with MAE = 99.0 ± 14.9 HU, but still inferior to the performance of the Baseline+FLAIR model (MAE = 72.6 ± 10.1 HU). Similarly, an improvement in γ-pass rate was obtained for DR vs Baseline. CONCLUSION: DR improved image similarity and dose accuracy on the unseen sequence compared to training only on acquired MRI. DR makes the model more robust, reducing the need for re-training when applying a model on sequences unseen and unavailable for retraining

Morphological analysis of the sheathed flagellum of Brucella melitensis

<p>Abstract</p> <p>Background</p> <p>It was recently shown that <it>B. melitensis </it>is flagellated. However, the flagellar structure remains poorly described.</p> <p>Findings</p> <p>We analyzed the structure of the polar sheathed flagellum of <it>B. melitensis </it>by TEM analysis and demonstrated that the Ryu staining is a good method to quickly visualize the flagellum by optical microscopy. The TEM analysis demonstrated that an extension of the outer membrane surrounds a filament ending by a club-like structure. The Δ<it>ftcR</it>, Δ<it>fliF</it>, Δ<it>flgE </it>and Δ<it>fliC </it>flagellar mutants still produce an empty sheath.</p> <p>Conclusions</p> <p>Our results demonstrate that the flagellum of <it>B. melitensis </it>has the characteristics of the sheathed flagella. Our results also suggest that the flagellar sheath production is not directly linked to the flagellar structure assembly and is not regulated by the FtcR master regulator.</p

In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed around Brucella Infected Cells in Resistant and Susceptible Mice

Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b+ F4/80+ MHC-II+ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS+ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis

Comparative Proteomics Analyses Reveal the virB of B. melitensis Affects Expression of Intracellular Survival Related Proteins

BACKGROUND: Brucella melitensis is a facultative, intracellular, pathogenic bacterium that replicates within macrophages. The type IV secretion system encoded by the virB operon (virB) is involved in Brucella intracellular survival. However, the underlying molecular mechanisms, especially the target proteins affected by the virB, remain largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: In order to define the proteins affected by virB, the proteomes of wild-type and the virB mutant were compared under in vitro conditions where virB was highly activated. The differentially expressed proteins were identified by MALDI-TOF-MS. Forty-four down-regulated and eighteen up-regulated proteins which exhibited a 2-fold or greater change were identified. These proteins included those involved in amino acid transport and metabolism, lipid metabolism, energy production, cell membrane biogenesis, translation, post-translational modifications and protein turnover, as well as unknown proteins. Interestingly, several important virulence related proteins involved in intracellular survival, including VjbR, DnaK, HtrA, Omp25, and GntR, were down-regulated in the virB mutant. Transcription analysis of virB and vjbR at different growth phase showed that virB positively affect transcription of vjbR in a growth phase dependent manner. Quantitative RT-PCR showed that transcription of these genes was also affected by virB during macrophage cell infection, consistent with the observed decreased survival of the virB mutant in macrophage. CONCLUSIONS/SIGNIFICANCE: These data indicated that the virB operon may control the intracellular survival of Brucella by affecting the expression of relevant proteins

Bank regulation and systemic risk: cross country evidence

Using data for banks from 65 countries for the period 2001–2013, we investigate the impact of bank regulation and supervision on individual banks’ systemic risk. Our cross-country empirical findings show that bank activity restriction, initial capital stringency and prompt corrective action are all positively related to systemic risk, measured by Marginal Expected Shortfall. We use the staggered timing of the implementation of Basel II regulation across countries as an exogenous event and use latitude for instrumental variable analysis to alleviate the endogeneity concern. Our results also hold for various robustness tests. We further find that the level of equity banks can alleviate such effect, while bank size is likely to enhance the effect, supporting our conjecture that the impact of bank regulation and supervision on systemic risk is through bank’s capital shortfall. Our results do not argue against bank regulation, but rather focus on the design and implementation of regulation

Complementing Bagehot: Illiquidity and insolvency resolution

During the recent financial crisis, central banks have provided liquidity and governments have set up rescue programmes to restore confidence and stability, often against the LLR principle advocated by Bagehot. Using a model of a systemic bank suffering from liquidity shocks, we find that the unregulated bank keeps too much liquidity and monitors too little. A central bank can alleviate the liquidity problem, but induces moral hazard. Therefore, we introduce an additional authority that is able to bail out the bank either by injecting capital at a fixed return or by receiving an equity claim. This authority faces a trade-off: demanding a fixed premium increases investment but worsens moral hazard. Request for an equity claim by the fiscal authority reduces excessive risk taking at the expense of investment. This resembles the current situation on financial markets, in which banks take less risk but also provide less credit to the economyBailout; Bank Regulation; Capital; Lender of Last Resort; Liquidity