Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio as Risk Factors for Venous Thrombosis

High platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) are associated with an increased risk of arterial thrombosis, but their role in venous thromboembolism (VTE) has not been fully investigated. A case\ue2\u80\u93control study, of 486 patients with VTE, 100 with cerebral vein thrombosis (CVT), and 299 healthy individuals, was carried out to investigate whether high PLR or NLR values are associated with an increased risk of VTE. Patients with high PLR or NLR did not have an increased risk of VTE (odds ratio [OR] 0.89, 95% confidence interval [CI]: 0.46-1.76; OR: 0.69, 95% CI: 0.34-1.39, respectively) or CVT (OR: 1.65, 95% CI: 0.68-4.00; OR: 0.39, 95% CI: 0.09-1.72, respectively). Subgroups analysis showed that high PLR values were associated with the risk of provoked CVT (OR: 2.65, 95% CI: 1.02-6.92), and there was an interaction with thrombophilia abnormalities (OR: 7.67, 95% CI: 1.67-35.27) in patients with CVT. In conclusion, high PLR and NLR values are not associated with an overall increased risk of VTE or CVT. High PLR values increase the risk of provoked CVT and interact with thrombophilia abnormalities in patients with CVT

Ionospheric anomalies detected by ionosonde and possibly related to crustal earthquakes in Greece

Ionosonde data and crustal earthquakes with magnitude M > 6:0 observed in Greece during the 2003–2015 period were examined to check if the relationships obtained earlier between precursory ionospheric anomalies and earthquakes in Japan and central Italy are also valid for Greek earthquakes. The ionospheric anomalies are identified on the observed variations of the sporadic E-layer parameters (h0Es, foEs) and foF2 at the ionospheric station of Athens. The corresponding empirical relationships between the seismoionospheric disturbances and the earthquake magnitude and the epicentral distance are obtained and found to be similar to those previously published for other case studies. The large lead times found for the ionospheric anomalies occurrence may confirm a rather long earthquake preparation period. The possibility of using the relationships obtained for earthquake prediction is finally discussed.Published361–3712A. Fisica dell'alta atmosferaJCR Journa

Towards quantum 3d imaging devices

We review the advancement of the research toward the design and implementation of quantum plenoptic cameras, radically novel 3D imaging devices that exploit both momentum–position entanglement and photon–number correlations to provide the typical refocusing and ultra-fast, scanning-free, 3D imaging capability of plenoptic devices, along with dramatically enhanced performances, unattainable in standard plenoptic cameras: diffraction-limited resolution, large depth of focus, and ultra-low noise. To further increase the volumetric resolution beyond the Rayleigh diffraction limit, and achieve the quantum limit, we are also developing dedicated protocols based on quantum Fisher information. However, for the quantum advantages of the proposed devices to be effective and appealing to end-users, two main challenges need to be tackled. First, due to the large number of frames required for correlation measurements to provide an acceptable signal-to-noise ratio, quantum plenoptic imaging (QPI) would require, if implemented with commercially available high-resolution cameras, acquisition times ranging from tens of seconds to a few minutes. Second, the elaboration of this large amount of data, in order to retrieve 3D images or refocusing 2D images, requires high-performance and time-consuming computation. To address these challenges, we are developing high-resolution single-photon avalanche photodiode (SPAD) arrays and high-performance low-level programming of ultra-fast electronics, combined with compressive sensing and quantum tomography algorithms, with the aim to reduce both the acquisition and the elaboration time by two orders of magnitude. Routes toward exploitation of the QPI devices will also be discussed

Magnetic Field and Electron Density Data Analysis from Swarm Satellites Searching for Ionospheric Effects by Great Earthquakes: 12 Case Studies from 2014 to 2016

We analyse Swarm satellite magnetic field and electron density data one month before and one month after 12 strong earthquakes that have occurred in the first 2.5 years of Swarm satellite mission lifetime in the Mediterranean region (magnitude M6.1+) or in the rest of the world (M6.7+). The search for anomalies was limited to the area centred at each earthquake epicentre and bounded by a circle that scales with magnitude according to the Dobrovolsky’s radius. We define the magnetic and electron density anomalies statistically in terms of specific thresholds with respect to the same statistical quantity along the whole residual satellite track (|geomagnetic latitude| ≤ 50°, quiet geomagnetic conditions). Once normalized by the analysed satellite tracks, the anomalies associated to all earthquakes resemble a linear dependence with earthquake magnitude, so supporting the statistical correlation with earthquakes and excluding a relationship by chance.PublishedID 3711A. Geomagnetismo e PaleomagnetismoJCR Journa

Restoring tumour selectivity of the bioreductive prodrug pr-104 by developing an analogue resistant to aerobic metabolism by human aldo-keto reductase 1c3

PR-104 is a phosphate ester pre-prodrug that is converted in vivo to its cognate alcohol, PR-104A, a latent alkylator which forms potent cytotoxins upon bioreduction. Hypoxia selectivity results from one-electron nitro reduction of PR-104A, in which cytochrome P450 oxidoreductase (POR) plays an important role. However, PR-104A also undergoes ‘off-target’ two-electron reduction by human aldo-keto reductase 1C3 (AKR1C3), resulting in activation in oxygenated tissues. AKR1C3 expression in human myeloid progenitor cells probably accounts for the dose-limiting myelotoxicity of PR-104 documented in clinical trials, resulting in human PR-104A plasma exposure levels 3.4- to 9.6-fold lower than can be achieved in murine models. Structure-based design to eliminate AKR1C3 activation thus represents a strategy for restoring the therapeutic window of this class of agent in humans. Here, we identified SN29176, a PR-104A analogue resistant to human AKR1C3 activation. SN29176 retains hypoxia selectivity in vitro with aerobic/hypoxic IC(50) ratios of 9 to 145, remains a substrate for POR and triggers γH2AX induction and cell cycle arrest in a comparable manner to PR-104A. SN35141, the soluble phosphate pre-prodrug of SN29176, exhibited superior hypoxic tumour log cell kill (>4.0) to PR-104 (2.5–3.7) in vivo at doses predicted to be achievable in humans. Orthologues of human AKR1C3 from mouse, rat and dog were incapable of reducing PR-104A, thus identifying an underlying cause for the discrepancy in PR-104 tolerance in pre-clinical models versus humans. In contrast, the macaque AKR1C3 gene orthologue was able to metabolise PR-104A, indicating that this species may be suitable for evaluating the toxicokinetics of PR-104 analogues for clinical development. We confirmed that SN29176 was not a substrate for AKR1C3 orthologues across all four pre-clinical species, demonstrating that this prodrug analogue class is suitable for further development. Based on these findings, a prodrug candidate was subsequently identified for clinical trials

Synthesis and down conversion emission property of Eu3+ doped LaAlO3 CsAlO2 and LiLaO2 phosphors

[EN] LaAlO3:Eu3+, CsAlO2:Eu3+ and LiLaO2:Eu3+ phosphors with varying concen- trations of Eu3+ from 3 to 10 mol% were prepared by combustion synthesis method and the samples were further heated to 1,000ºC to improve the crystallinity of the materials. The structure and morphology of materials have been examined by X-ray diffraction and scan- ning electron microscopy. SEM images depicted that the morphology of crystallites have no uniform shapes and sizes. Small and coagulated particles of irregular shapes of different sizes are obtained. The characteristic emissions of Eu3+ were clearly observed at nearly 580, 592, 650, 682 to 709 (multiplet structure) nm for 5D - 7 Fn transitions where n = 0, 1, 3, 4 respectively, including the strongest emission peaks at 614 and 620 nm for 5 D0 - 7 F2 transitions in CsAlO2:Eu3+ and LiLaO2:Eu3+ host lattices. The intensity of emission peak corresponding to 5 D0 !→ 7 F1 transitions in LaAlO3 :Eu3+ material is comparable to that of 5D0 5D-7F2 transitions which is also a singlet. Photoluminescence intensity follows the order as in LiLaO2 > LaAlO3 > CsAlO2 lattices. Remarkable high photoluminescence intensity with 7 mol% doping of Eu3+ in LiLaO2 makes it a strong contender for red colored display applications.This work was supported by the European Commission through Nano CIS project (FP7-PEOPLE-2010-IRSES ref. 269279).Marí Soucase, B.; Singh, KC.; Moya Forero, MM.; Singh, I.; Om, H.; Chand, S. (2015). Synthesis and down conversion emission property of Eu3+ doped LaAlO3 CsAlO2 and LiLaO2 phosphors. Optical and Quantum Electronics. 47(7):1569-1578. https://doi.org/10.1007/s11082-014-9997-9S15691578477Abbattista, F., Vallino, M.: Remarks on the $$\text{La}_{2}\text{O}_{3}-\text{Li}_{2}\text{O}$$ La 2 O 3 - Li 2 O binary system between 750 and 1,000  $$^{\circ}$$ ∘ C. Ceram. 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Targeting the hypoxic fraction of tumours using hypoxia activated prodrugs

The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high priority target and one therapeutic strategies designed to eradicate hypoxic cells in tumours are a group of compounds known collectively as hypoxia activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (i) the ability of oxygen to either reverse or inhibit the activation process and (ii) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples

Rivaroxaban Compared with Standard Anticoagulants for the Treatment of Acute Venous Thromboembolism in Children: a Randomised, Controlled, Phase 3 Trial

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0–17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. Findings: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87–95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29–35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11–1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51–6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. Interpretation: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. Funding: Bayer AG and Janssen Research & Development. © 2020 Elsevier Ltd