Imaging of X-Ray-Excited Emissions from Quantum Dots and Biological Tissue in Whole Mouse

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering and absorption limit the depth and resolution in both animal and human subjects. Two new hybrid approaches are presented, using the penetrating power of X-rays to increase the depth of optical imaging. Foremost, we demonstrate the excitation by X-rays of quantum-dots (QD) emitting in the near-infrared (NIR), using a clinical X-ray system to map the distribution of QDs at depth in whole mouse. We elicit a clear, spatially-resolved NIR signal from deep organs (brain, liver and kidney) with short (1 second) exposures and tolerable radiation doses that will permit future in vivo applications. Furthermore, X-ray-excited endogenous emission is also detected from whole mouse. The use of keV X-rays to excite emission from QDs and tissue represent novel biomedical imaging technologies, and exploit emerging QDs as optical probes for spatial-temporal molecular imaging at greater depth than previously possible.Peer reviewe

The time-dependent rearrangement of the epithelial basement membrane in human skin wounds

In 62 human skin wounds (surgical wounds, stab wounds and lacerations after surgical treatment) we analyzed the immunohistochemical localization of collagen IV in the epithelial basement membrane. In 27 of these wounds the distribution of collagen VII, which represents a specific component of the basement membrane of stratified epithelia, was also analyzed. We were able to demonstrate a virtually identical co-distribution of both collagen IV and VII in the wound area with no significant time-dependent differences in the appearance of both collagen types. Fragments of the epithelial basement membrane could be detected in the wound area from as early as 4 days after wounding and after 8 days a complete restitution of the epithelial basement membrane was observed. In all cases with a wound age of more than 21 days the basement membrane was completely reformed over the former lesional area. The period between 8 and 21 days after wounding was characterized by a wide variability ranging from complete restitution to deposition of basement membrane fragments or total lack of the epidermal basement membrane

Direct exfoliation and dispersion of two-dimensional materials in pure water via temperature control

The high-volume synthesis of two-dimensional (2D) materials in the form of platelets is desirable for various applications. While water is considered an ideal dispersion medium, due to its abundance and low cost, the hydrophobicity of platelet surfaces has prohibited its widespread use. Here we exfoliate 2D materials directly in pure water without using any chemicals or surfactants. In order to exfoliate and disperse the materials in water, we elevate the temperature of the sonication bath, and introduce energy via the dissipation of sonic waves. Storage stability greater than one month is achieved through the maintenance of high temperatures, and through atomic and molecular level simulations, we further discover that good solubility in water is maintained due to the presence of platelet surface charges as a result of edge functionalization or intrinsic polarity. Finally, we demonstrate inkjet printing on hard and flexible substrates as a potential application of water-dispersed 2D materials.close1

Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Malaltia d'Alzheimer; Apolipoproteïnes; Angiopatia amiloide cerebralEnfermedad de Alzheimer; Apolipoproteínas; Angiopatía amiloide cerebralAlzheimer’s disease; Apolipoproteins; Cerebral amyloid angiopathyCerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer’s disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.This research was funded by Instituto de Salud Carlos III (co-financed by the European Regional Development Fund FEDER “Una manera de hacer Europa”), grant numbers PI13/00364, PI16/00471, PI14/01134 and PI17/00275. A.R.-U. was funded by Instituto de Salud Carlos III predoctoral contract FI17/00031. The Neurovascular Research Laboratory is part of the INVICTUS+ network, ISCIII, Spain [RD16/0019/0021]. J.L.S.-Q. is a member of the CIBER of Diabetes and Metabolism (CIBERDEM), ISCIII, Spain. M.H.-G. is supported by the Miguel Servet programme, ISCIII, Spain [CPII17/00010]. A.R.-U., N.P., S.B. and J.L.S.-Q. are members of the Quality Research Group 2017-SGR-1149 from Generalitat de Catalunya. A.R.-U., N.P., S.B. and J.L.S.-Q. are members of the Group of Vascular Biology from the Spanish Atherosclerosis Society

Brain age predicts mortality

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death

DESIGN OF AN INTEGRATED AGRARIAN DATA DIMENSIONAL DATA WAREHOUSE

The concept of the Data warehouse was developed to provide a single access point to data from a variety of sources. There isa need to have a single location for the storage and sharing of data that users can easily utilize to make effective and qualitybusiness decisions, rather than trying to traverse the multiple data sources that exist today. Although many frameworks havebeen developed to integrate these sources into a single database, a reliable framework has yet to be developed. A majorhindrance to achieving a reliable warehouse is the poor quality of data obtained from the data transformation stage in theextract, transfer and load process. This poor quality of data contributes to inaccurate and unreliable results and if this data isused for decision making, unforeseen critical business errors can occur. This work reviews the data integration andtransformation process in dimensional data warehouses and proposes a dual structure for data integration and metadata ofmulti-formatted data used for the design of dimensional data warehouse using Agrarian data collected from Ondo State,Nigeria as a case study.Keywords: Data Warehouse, Data Integration, Metadata, Agrarian data

New prioritized value iteration for Markov decision processes

The problem of solving large Markov decision processes accurately and quickly is challenging. Since the computational effort incurred is considerable, current research focuses on finding superior acceleration techniques. For instance, the convergence properties of current solution methods depend, to a great extent, on the order of backup operations. On one hand, algorithms such as topological sorting are able to find good orderings but their overhead is usually high. On the other hand, shortest path methods, such as Dijkstra's algorithm which is based on priority queues, have been applied successfully to the solution of deterministic shortest-path Markov decision processes. Here, we propose an improved value iteration algorithm based on Dijkstra's algorithm for solving shortest path Markov decision processes. The experimental results on a stochastic shortest-path problem show the feasibility of our approach. © Springer Science+Business Media B.V. 2011.García Hernández, MDG.; Ruiz Pinales, J.; Onaindia De La Rivaherrera, E.; Aviña Cervantes, JG.; Ledesma Orozco, S.; Alvarado Mendez, E.; Reyes Ballesteros, A. (2012). New prioritized value iteration for Markov decision processes. Artificial Intelligence Review. 37(2):157-167. doi:10.1007/s10462-011-9224-zS157167372Agrawal S, Roth D (2002) Learning a sparse representation for object detection. In: Proceedings of the 7th European conference on computer vision. Copenhagen, Denmark, pp 1–15Bellman RE (1954) The theory of dynamic programming. Bull Amer Math Soc 60: 503–516Bellman RE (1957) Dynamic programming. Princeton University Press, New JerseyBertsekas DP (1995) Dynamic programming and optimal control. Athena Scientific, MassachusettsBhuma K, Goldsmith J (2003) Bidirectional LAO* algorithm. In: Proceedings of indian international conferences on artificial intelligence. p 980–992Blackwell D (1965) Discounted dynamic programming. Ann Math Stat 36: 226–235Bonet B, Geffner H (2003a) Faster heuristic search algorithms for planning with uncertainty and full feedback. In: Proceedings of the 18th international joint conference on artificial intelligence. Morgan Kaufmann, Acapulco, México, pp 1233–1238Bonet B, Geffner H (2003b) Labeled RTDP: improving the convergence of real-time dynamic programming. In: Proceedings of the international conference on automated planning and scheduling. Trento, Italy, pp 12–21Bonet B, Geffner H (2006) Learning depth-first search: a unified approach to heuristic search in deterministic and non-deterministic settings and its application to MDP. In: Proceedings of the 16th international conference on automated planning and scheduling. Cumbria, UKBoutilier C, Dean T, Hanks S (1999) Decision-theoretic planning: structural assumptions and computational leverage. J Artif Intell Res 11: 1–94Chang I, Soo H (2007) Simulation-based algorithms for Markov decision processes Communications and control engineering. Springer, LondonDai P, Goldsmith J (2007a) Faster dynamic programming for Markov decision processes. Technical report. Doctoral consortium, department of computer science and engineering. University of WashingtonDai P, Goldsmith J (2007b) Topological value iteration algorithm for Markov decision processes. In: Proceedings of the 20th international joint conference on artificial intelligence. Hyderabad, India, pp 1860–1865Dai P, Hansen EA (2007c) Prioritizing bellman backups without a priority queue. In: Proceedings of the 17th international conference on automated planning and scheduling, association for the advancement of artificial intelligence. Rhode Island, USA, pp 113–119Dibangoye JS, Chaib-draa B, Mouaddib A (2008) A Novel prioritization technique for solving Markov decision processes. In: Proceedings of the 21st international FLAIRS (The Florida Artificial Intelligence Research Society) conference, association for the advancement of artificial intelligence. Florida, USAFerguson D, Stentz A (2004) Focused propagation of MDPs for path planning. In: Proceedings of the 16th IEEE international conference on tools with artificial intelligence. pp 310–317Hansen EA, Zilberstein S (2001) LAO: a heuristic search algorithm that finds solutions with loops. Artif Intell 129: 35–62Hinderer K, Waldmann KH (2003) The critical discount factor for finite Markovian decision processes with an absorbing set. Math Methods Oper Res 57: 1–19Li L (2009) A unifying framework for computational reinforcement learning theory. PhD Thesis. The state university of New Jersey, New Brunswick. NJLittman ML, Dean TL, Kaelbling LP (1995) On the complexity of solving Markov decision problems.In: Proceedings of the 11th international conference on uncertainty in artificial intelligence. Montreal, Quebec pp 394–402McMahan HB, Gordon G (2005a) Fast exact planning in Markov decision processes. In: Proceedings of the 15th international conference on automated planning and scheduling. Monterey, CA, USAMcMahan HB, Gordon G (2005b) Generalizing Dijkstra’s algorithm and gaussian elimination for solving MDPs. Technical report, Carnegie Mellon University, PittsburghMeuleau N, Brafman R, Benazera E (2006) Stochastic over-subscription planning using hierarchies of MDPs. In: Proceedings of the 16th international conference on automated planning and scheduling. Cumbria, UK, pp 121–130Moore A, Atkeson C (1993) Prioritized sweeping: reinforcement learning with less data and less real time. Mach Learn 13: 103–130Puterman ML (1994) Markov decision processes. Wiley Editors, New YorkPuterman ML (2005) Markov decision processes. Wiley Inter Science Editors, New YorkRussell S (2005) Artificial intelligence: a modern approach. Making complex decisions (Ch-17), 2nd edn. Pearson Prentice Hill Ed., USAShani G, Brafman R, Shimony S (2008) Prioritizing point-based POMDP solvers. IEEE Trans Syst Man Cybern 38(6): 1592–1605Sniedovich M (2006) Dijkstra’s algorithm revisited: the dynamic programming connexion. Control Cybern 35: 599–620Sniedovich M (2010) Dynamic programming: foundations and principles, 2nd edn. Pure and Applied Mathematics Series, UKTijms HC (2003) A first course in stochastic models. Discrete-time Markov decision processes (Ch-6). Wiley Editors, UKVanderbei RJ (1996) Optimal sailing strategies. Statistics and operations research program, University of Princeton, USA ( http://www.orfe.princeton.edu/~rvdb/sail/sail.html )Vanderbei RJ (2008) Linear programming: foundations and extensions, 3rd edn. Springer, New YorkWingate D, Seppi KD (2005) Prioritization methods for accelerating MDP solvers. J Mach Learn Res 6: 851–88

Use of Intravenous Peramivir for Treatment of Severe Influenza A(H1N1)pdm09

Oral antiviral agents to treat influenza are challenging to administer in the intensive care unit (ICU). We describe 57 critically ill patients treated with the investigational intravenous neuraminidase inhibitor drug peramivir for influenza A (H1N1)pdm09 [pH1N1]. Most received late peramivir treatment following clinical deterioration in the ICU on enterically-administered oseltamivir therapy. The median age was 40 years (range 5 months-81 years). Common clinical complications included pneumonia or acute respiratory distress syndrome requiring mechanical ventilation (54; 95%), sepsis requiring vasopressor support (34/53; 64%), acute renal failure requiring hemodialysis (19/53; 36%) and secondary bacterial infection (14; 25%). Over half (29; 51%) died. When comparing the 57 peramivir-treated cases with 1627 critically ill cases who did not receive peramivir, peramivir recipients were more likely to be diagnosed with pneumonia/acute respiratory distress syndrome (p = 0.0002) or sepsis (p = <0.0001), require mechanical ventilation (p = <0.0001) or die (p = <0.0001). The high mortality could be due to the pre-existing clinical severity of cases prior to request for peramivir, but also raises questions about peramivir safety and effectiveness in hospitalized and critically ill patients. The use of peramivir merits further study in randomized controlled trials, or by use of methods such as propensity scoring and matching, to assess clinical effectiveness and safety

Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug–Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA)

Purpose: The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Patients and Methods: This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017–March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with ≥2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool. Results: A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p 50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with ≥2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with ≥2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients). Conclusion: This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/ VEL regimen was more frequently detected on elderly patients and on those with ≥2 comedications at risk of multi-DDI, ie, among patients characterized by higher rates of comorbidities and polypharmacy

Synthesis, Electrical Measurement, and Field Emission Properties of α-Fe2O3Nanowires

α-Fe2O3nanowires (NWs) were formed by the thermal oxidation of an iron film in air at 350 °C for 10 h. The rhombohedral structure of the α-Fe2O3NWs was grown vertically on the substrate with diameters of 8–25 nm and lengths of several hundred nm. It was found that the population density of the NWs per unit area (DNWs) can be varied by the film thickness. The thicker the iron film, the more NWs were grown. The growth mechanism of the NWs is suggested to be a combination effect of the thermal oxidation rate, defects on the film, and selective directional growth. The electrical resistivity of a single NW with a length of 800 nm and a diameter of 15 nm was measured to be 4.42 × 103 Ωcm using conductive atomic force microscopy. The field emission characteristics of the NWs were studied using a two-parallel-plate system. A low turn–on field of 3.3 V/μm and a large current density of 10−3 A/cm2(under an applied field of about 7 V/μm) can be obtained using optimal factors ofDNWsin the cathode