Robust 3D U-Net Segmentation of Macular Holes

Macular holes are a common eye condition which result in visual impairment. We look at the application of deep convolutional neural networks to the problem of macular hole segmentation. We use the 3D U-Net architecture as a basis and experiment with a number of design variants. Manually annotating and measuring macular holes is time consuming and error prone. Previous automated approaches to macular hole segmentation take minutes to segment a single 3D scan. Our proposed model generates significantly more accurate segmentations in less than a second. We found that an approach of architectural simplification, by greatly simplifying the network capacity and depth, exceeds both expert performance and state-of-the-art models such as residual 3D U-Nets

Measuring diffuse neutrino fluxes with IceCube

In this paper the sensitivity of a future kilometer-sized neutrino detector to detect and measure the diffuse flux of high energy neutrinos is evaluated. Event rates in established detection channels, such as muon events from charged current muon neutrino interactions or cascade events from electron neutrino and tau neutrino interactions, are calculated using a detailed Monte Carlo simulation. Neutrino fluxes as expected from prompt charm decay in the atmosphere or from astrophysical sources such as Active Galactic Nuclei are modeled assuming power laws. The ability to measure the normalization and slope of these spectra is then analyzed. It is found that the cascade channel generally has a high sensitivity for the detection and characterization of the diffuse flux, when compared to what is expected for the upgoing- and downgoing-muon channels. A flux at the level of the Waxman-Bahcall upper bound should be detectable in all channels separately while a combination of the information of the different channels will allow detection of a flux more than one order of magnitude lower. Neutrinos from the prompt decay of charmed mesons in the atmosphere should be detectable in future measurements for all but the lowest predictions.Comment: 12 pages, 3 figure

Physical and psychological paths toward less severe fibromyalgia: A structural equation model

The authors gratefully acknowledge all the participants for their collaboration and enthusiasm. We thank the assistant researchers involved in this study and all the members of the Physical Activity for HEaLth Promotion (PA-HELP; CTS-1018) research group.Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j.rehab.2019.06.017.Objectives: Previous research suggested isolated associations of physical and psychological factors with fibromyalgia severity. Integration of physical and psychological, experienced and observed, modifiable factors associated with fibromyalgia severity in a single model will reveal therapeutic paths toward less severity of disease. We aimed to examine an encompassing model of determinants of fibromyalgia severity. Methods: This observational, population-based cross-sectional study included 569 people with fibromyalgia. An integrative model of fibromyalgia severity was tested by using structural equation modelling. This model included 8 factors: resilience, catastrophizing, active lifestyle, declarative memory, subjective fitness, objective fitness, psychological distress, and physical fatigue. Results: Two core paths were associated with reduced fibromyalgia severity: 1) a psychological path connecting high resilience and low catastrophizing with low distress and 2) a physical path, connecting a more active lifestyle (directly and via high objective and subjective physical fitness) with low fatigue. Additional interconnecting paths especially suggested a connection from the psychological to physical path. Our model explained 83% of the fibromyalgia severity. Conclusions: The present model integrated the complexity of mutually influencing factors of fibromyalgia severity, which may help to better understand the disease. It emphasised the importance of: 1) physical factors and psychological factors and their interconnections, 2) patients’ experiences and clinical measurements, and 3) positive and negative signs such as physical fitness and distress. Future longitudinal and experimental research should aim at testing the causal direction of the associations in the model as well as the clinical implications suggested by the model. For instance, to reduce fatigue, exercise should enhance not only objective fitness but also fitness-related perceptions. Reducing distress and fatigue seems crucial for lowering fibromyalgia severity.This work was supported by the Spanish Ministry of Economy and Competitiveness [I+D+i DEP2010-15639, I+D+I DEP2013-40908, I+D+I PSI2015-65241-R, and BES-2014-067612] and the Spanish Ministry of Education [FPU15/00002]. This study was funded in part by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ref. SOMM17/6107/UGR) and University of Jaén, Plan de Apoyo a la Investigación 2017-2019 [EI_SEJ07_2017]. The funders did not have any role in the study design, data collection and analyses, decision to publish, or preparation of the manuscript

Neurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines

Abstract Neurohypophysial oxytocin (OT) and vasopressin (VP) genes are transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+ CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment

TiO2 Photocatalyzed Oxidation of Drugs Studied by Laser Ablation Electrospray Ionization Mass Spectrometry

In drug discovery, it is important to identify phase I metabolic modifications as early as possible to screen for inactivation of drugs and/or activation of prodrugs. As the major class of reactions in phase I metabolism is oxidation reactions, oxidation of drugs with TiO2 photocatalysis can be used as a simple non-biological method to initially eliminate (pro)drug candidates with an undesired phase I oxidation metabolism. Analysis of reaction products is commonly achieved with mass spectrometry coupled to chromatography. However, sample throughput can be substantially increased by eliminating pretreatment steps and exploiting the potential of ambient ionization mass spectrometry (MS). Furthermore, online monitoring of reactions in a time-resolved way would identify sequential modification steps. Here, we introduce a novel (time-resolved) TiO2-photocatalysis laser ablation electrospray ionization (LAESI) MS method for the analysis of drug candidates. This method was proven to be compatible with both TiO2-coated glass slides as well as solutions containing suspended TiO2 nanoparticles, and the results were in excellent agreement with studies on biological oxidation of verapamil, buspirone, testosterone, andarine, and ostarine. Finally, a time-resolved LAESI MS setup was developed and initial results for verapamil showed excellent analytical stability for online photocatalyzed oxidation reactions within the set-up up to at least 1h.Peer reviewe