Empirical Assessment of Breast Lesion Detection Capability Through an Innovative Microwave Imaging Device

This paper investigates the effect of conductivity weighting on microwave images obtained through a dedicated imaging device. MammoWave is a microwave imaging device for detection of breast lesions, operating using only two azimuthally rotating antennas without the use of matching liquids. For each breast, a set of conductivity weighted images are generated through modifying our algorithm based on Huygens principle, producing intensity maps representing the homogeneity of tissues’ dielectric properties. Subsequently, we introduce several imaging parameters (i.e. features) to quantify the non-homogenous behaviour of the image. Through empirical investigation on 103 breasts, we can verify that a selection of these features could allow distinction between breasts with radiological findings (WF), i.e. with benign or malign lesions, and breasts with no radiological findings (NF). Statistical significance was set at p<0.05.We obtained single features Area Under the receiver operating characteristic Curves (AUCs) spanning from 0.65 to 0.68. Significantly, we achieve AUCs of up to 0.77 when considering dense breasts only, which tend to cause detection limitations in mammography exams

Shaking Scenarios from Multiple Source Models Shed Light on the 8 September 1905 Mw 7 Calabria Earthquake (Southern Italy)

4noThe earthquake (Mw 7) that struck western Calabria (southern Italy) on 8 September 1905 profoundly struck a broad region, causing 557 deaths, injuring more than 2000 people, and leaving about 300,000 people homeless. Historical documents also reported a tsunami, although not devastating, for which effects were observed both along the coast and offshore. For all the damage it caused, this event was much studied but not fully explained. Literature source models for the 1905 earthquake are numerous and diverse, in fault geometry, location, and even associated magnitude. They also differ in nature, because these solutions are either field-based or derived from tsunami modeling and macroseismic data inversion. Above all, few or none of the previously published source models appear to be fully compatible with the damage pattern caused by this earthquake. To contribute to the identification of the seismogenic source of this destructive event, we computed a series of ground-shaking scenarios based on the different fault-source models that various authors associated with this event. The only documented data available that are suitable for our comparative purposes are the macroseismic intensities associated with localities affected by the event. Our results show that shaking scenarios for two out of seven literature source models are compatible with the damage distribution caused by the 1905 earthquake. The different parameters and boundary conditions constraining these two solutions suggest that either seismogenic source should include further complexities. Alternatively, because these two sources are antithetic and partially form a graben, they might have kinematically interacted, if passively, on 8 September 1905. Also, our critical analysis attempts to take site effects into account, at least qualitatively, allowing a more robust evaluation of damage distribution against numerical models.openembargoed_20160430Sandron, Denis; Loreto, Maria Filomena; Fracassi, Umberto; Tiberi, LaraSandron, Denis; Loreto, Maria Filomena; Fracassi, Umberto; Tiberi, Lar

HCO3−/Cl− Exchange Inactivation and Reactivation during Mouse Oocyte Meiosis Correlates with MEK/MAPK-Regulated Ae2 Plasma Membrane Localization

Background: Germinal Vesicle (GV) stage mouse oocytes in first meiotic prophase exhibit highly active HCO3−/Cl− exchange—a class of transport nearly ubiquitously involved in regulation of intracellular pH and cell volume. During meiosis, however, oocyte HCO3−/Cl− exchange becomes inactivated during first metaphase (MI), remains inactive in second metaphase (MII), and is reactivated only after egg activation. Previous work using pharmacological manipulations had indicated that activity of the MEK/MAPK signaling pathway was negatively correlated with HCO3−/Cl− exchange activity during meiosis. However, the mechanism by which the exchanger is inactivated during meiotic progression had not been determined, nor had the role of MEK/MAPK been directly established. Methodology/Principal Findings: Expression of a constitutively active form of MEK (MAP kinase kinase), which prevented the normal downregulation of MAPK after egg activation, also prevented reactivation of HCO3−/Cl− exchange. Conversely, suppression of endogenous MAPK activity with dominant negative MEK activated the normally quiescent HCO3−/Cl− exchange in mature MII eggs. A GFP-tagged form of the HCO3−/Cl− exchanger isoform Ae2 (Slc4a2) was strongly expressed at the GV oocyte plasma membrane, but membrane localization decreased markedly during meiotic progression. A similar pattern for endogenous Ae2 was confirmed by immunocytochemistry. The loss of membrane-localized Ae2 appeared selective, since membrane localization of a GFP-tagged human dopamine D1 receptor did not change during meiotic maturation. Conclusions: Direct manipulation of MAPK activity indicated that GFP-tagged Ae2 localization depended upon MAPK activity. Inactivation of HCO3−/Cl− exchange during the meiotic cell cycle may therefore reflect the loss of Ae2 from the oocyte plasma membrane, downstream of MEK/MAPK signaling. This identifies a novel role for MEK/MAPK-mediated cytostatic factor (CSF) activity during meiosis in membrane protein trafficking in mouse oocytes, and shows for the first time that selective retrieval of membrane proteins is a feature of meiosis in mammalian oocytes

distinct: a novel approach to differential distribution analyses

We present distinct, a general method for differential analysis of full distributions that is well suited to applications on single-cell data, such as single-cell RNA sequencing and high-dimensional flow or mass cytometry data. High-throughput single-cell data reveal an unprecedented view of cell identity and allow complex variations between conditions to be discovered; nonetheless, most methods for differential expression target differences in the mean and struggle to identify changes where the mean is only marginally affected. distinct is based on a hierarchical non-parametric permutation ap- proach and, by comparing empirical cumulative distribution functions, iden- tifies both differential patterns involving changes in the mean, as well as more subtle variations that do not involve the mean. We performed extensive bench- marks across both simulated and experimental datasets from single-cell RNA sequencing and mass cytometry data, where distinct shows favourable per- formance, identifies more differential patterns than competitors, and displays good control of false positive and false discovery rates. distinct is available as a Bioconductor R package

Bedaquiline in MDR/XDR-TB cases: first experience on compassionate use

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Applicability of the shorter 'Bangladesh regimen' in high multidrug-resistant tuberculosis settings

In spite of the recent introduction of two new drugs (delamanid and bedaquiline) and a few repurposed compounds to treat multidrug-resistant and extensively drug-resistant tuberculosis (MDR- and XDR-TB), clinicians are facing increasing problems in designing effective regimens in severe cases. Recently a 9 to 12-month regimen (known as the 'Bangladesh regimen') proved to be effective in treating MDR-TB cases. It included an initial phase of 4 to 6 months of kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol, followed by 5 months of moxifloxacin, clofazimine, pyrazinamide, and ethambutol. However, recent evidence from Europe and Latin America identified prevalences of resistance to the first-line drugs in this regimen (ethambutol and pyrazinamide) exceeding 60%, and of prothionamide exceeding 50%. Furthermore, the proportions of resistance to the two most important pillars of the regimen - quinolones and kanamycin - were higher than 40%. Overall, only 14 out of 348 adult patients (4.0%) were susceptible to all of the drugs composing the regimen, and were therefore potentially suitable for the 'shorter regimen'. A shorter, cheaper, and well-tolerated MDR-TB regimen is likely to impact the number of patients treated and improve adherence if prescribed to the right patients through the systematic use of rapid MTBDRsl testing

Machine Learning Approach for Care Improvement of Children and Youth with Type 1 Diabetes Treated with Hybrid Closed-Loop System

Type 1 diabetes is a disease affecting beta cells of the pancreas and it’s responsible for a decreased insulin secretion, leading to an increased blood glucose level. The traditional method for glucose treatment is based on finger-stick measurement of the blood glucose concentration and consequent manual insulin injection. Nowadays insulin pumps and continuous glucose monitoring systems are replacing them, being simpler and automatized. This paper focuses on analyzing and improving the knowledge about which Machine Learning algorithms can work best with glycaemic data and tries to find out the relation between insulin pump settings and glycaemic control. The dataset is composed of 90 days of recordings taken from 16 children and adolescents. Three Machine Learning approaches, two for classification, Logistic Regression (LR) and Random Forest (RL), and one for regression, Multivariate Linear Regression (MLR), have been used for the purpose. Specifically, the pump settings analysis was performed based on the Time In Range (TIR) computation and comparison consequent to pump setting changes. RF and MLR have shown the best results, while, for the settings’ analysis, the data show a discrete correlation between changes and TIRs. This study provides an interesting closer look at the data recorded by the insulin pump and a suitable starting point for a thorough and complete analysis of them

3D Huygens Principle based Microwave Imaging through MammoWave Device: Validation through Phantoms.

This work focuses on developing a 3D microwave imaging (MWI) algorithm based on the Huygens principle (HP). Specifically, a novel, fast MWI device (MammoWave) has been presented and exploited for its capabilities of extending image reconstruction from 2D to 3D. For this purpose, dedicated phantoms containing 3D structured inclusion have been prepared with mixtures having different dielectric properties. Phantom measurements have been performed at multiple planes along the z-axis by simultaneously changing the transmitter and receiver antenna height via the graphic user interface (GUI) integrated with MammoWave. We have recorded the complex S21 multi-quote data at multiple planes along the z-axis. The complex multidimensional raw data has been processed via an enhanced HP-based image algorithm for 3D image reconstruction. This paper demonstrates the successful detection and 3D visualization of the inclusion with varying dimensions at multiple planes/cross-sections along the z-axis with a dimensional error lower than 7.5%. Moreover, the paper shows successful detection and 3D visualization of the inclusion in a skull-mimicking phantom having a cylindrically shaped inclusion, with the location of the detected inclusion in agreement with the experimental setup. Additionally, the localization of a 3D structured spherical inclusion has been shown in a more complex scenario using a 3-layer cylindrically shaped phantom, along with the corresponding 3D image reconstruction and visualization

Effects of the load size on the maximum local SAR at 7T

In this study we investigated the effects of the load size on the maximum local SAR at 7T. Specifically, we resorted to: i) 3D full wave numerical electromagnetic simulations for analyzing a surface loop loaded with anatomic human calves models; ii) 2D analytical approach for analyzing a volume resonator loaded with homogeneous cylindrical phantoms having average tissue dielectric properties. In both cases we noticed that the maximum local SAR decreases with decreasing load size: this holds true if the RF magnetic fields (B1+) for the different load sizes are scaled so to achieve the same slice average value of 1ìT