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Background: Intra-articular injections of platelet-rich plasma (PRP) to treat symptoms of knee osteoarthritis (OA) have been successfully used in young patients and in the early stages of disease. No previous studies have analyzed outcomes of PRP injections during the late stages. Hypothesis: PRP reduces pain and leads to a more effective and lasting functional recovery than corticosteroid with local anesthetic. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 75 patients with symptomatic knee OA (Kellgren-Lawrence grade 3 to 4) were enrolled in this study between August 2013 and July 2014. Patients were randomized to treatment either with a single leukocyte-reduced PRP or corticosteroid intra-articular injection. The primary variable was visual analog scale assessment at 1 month. Secondary outcomes were the Knee injury and Osteoarthritis Outcome Score (KOOS) and Short Form–36 (SF-36) at 1, 3, and 6 months after treatment. Patient satisfaction at final follow-up was assessed. Both groups were homogeneous and comparable in baseline characteristics. Results: All variables improved in both groups. Statistical differences between groups were not found for the majority of the outcome variables, although the magnitude of improvements tended to be greater in the PRP group. Quality-of-life differences between values at 3 and 6 months versus baseline increased significantly more in the study group (P = .05 and .03, respectively), and so did general health perception differences at 6 months (P = .018). Conclusion: A single PRP intra-articular injection is effective for relieving pain and improving activities of daily living and quality of life in late-stage knee OA. For patients with late-stage knee OA who are 67 years or older, 1 intra-articular injection of PRP has similar results to 1 shot of corticosteroid.

In order to address the growing need for more accurate space-weather predictions, a new model named EUHFORIA (EUropean Heliospheric FORecasting Information Asset) was recently developed. We present the first results of the performance assessment for the solar-wind modeling with EUHFORIA and identify possible limitations of its present setup. Using the basic EUHFORIA 1.0.4 model setup with the default input parameters, we modeled background solar wind (no coronal mass ejections) and compared the obtained results with Advanced Composition Explorer (ACE) in-situ measurements. For the purposes of statistical study we developed a technique of combining daily EUHFORIA runs into continuous time series. The combined time series were derived for the years 2008 (low solar activity) and 2012 (high solar activity), from which in-situ speed and density profiles were extracted. We find for the low-activity phase a better match between model results and observations compared to the high-activity time interval considered. The quality of the modeled solar-wind parameters is found to be rather variable. Therefore, to better understand the results obtained we also qualitatively inspected characteristics of coronal holes, i.e. the sources of the studied fast streams. We discuss how different characteristics of the coronal holes and input parameters to EUHFORIA influence the modeled fast solar wind, and suggest possibilities for the improvement of the model.

This paper presents a review on the PECASUS service, which provides advisories on enhanced space weather activity for civil aviation. The advisories are tailored according to the Standards and Recommended Practices of the International Civil Aviation Organization (ICAO). Advisories are disseminated in three impact areas: radiation levels at flight altitudes, GNSS-based navigation and positioning, and HF communication. The review, which is based on the experiences of the authors from two years of running pilot ICAO services, describes empirical models behind PECASUS products and lists ground- and space-based sensors, providing inputs for the models and 24/7 manual monitoring activities. As a concrete example of PECASUS performance, its products for a post-storm ionospheric F2-layer depression event are analyzed in more detail. As PECASUS models are particularly tailored to describe F2-layer thinning, they reproduce observations more accurately than the International Reference Ionosphere model (IRI(STORM)), but, on the other hand, it is recognized that the service performance is much affected by the coverage of its input data. Therefore, more efforts will be directed toward systematic measuring of the availability, timeliness and quality of the data provision in the next steps of the service development.

Coronal mass ejections (CMEs),  in particular Earth-directed ones, are regarded as the main drivers of geomagnetic activity. In this study, we present a statistical analysis of a set of 53 fast ( V  ≥ 1000 km·s −1 ) Earth-directed halo CMEs observed by the SOHO/LASCO instrument during the period Jan. 2009–Sep. 2015, and we then use this CME sample to test the forecasting capabilities of a new Sun-to-Earth prediction scheme for the geoeffectiveness of Earth-directed halo CMEs. First, we investigate the CME association with other solar activity features such as solar flares, active regions, and others, by means of multi-instrument observations of the solar magnetic and plasma properties, with the final aim of identifying recurrent peculiar features that can be used as precursors of CME-driven geomagnetic storms. Second, using coronagraphic images to derive the CME kinematical properties at 0.1 AU, we propagate the events to 1 AU by means of 3D global MHD simulations. In particular, we use the WSA-ENLIL+Cone model to reconstruct the propagation and global evolution of each event up to their arrival at Earth, where simulation results are compared with interplanetary CME (ICME) in-situ signatures. We then use simulation outputs upstream of Earth to predict their impact on geospace. By applying the pressure balance condition at the magnetopause and the coupling function proposed by Newell et al. [ J Geophys Res: Space Phys 113 (2008)] to link upstream solar wind properties to the global K p index, we estimate the expected magnetospheric compression and geomagnetic activity level, and compare our predictions with global data records. The analysis indicates that 82% of the fast Earth-directed halo CMEs arrived at Earth within the next 4 days. Almost the totality of them compressed the magnetopause below geosynchronous orbits and triggered a minor or major geomagnetic storm afterwards. Among them, complex sunspot-rich active regions associated with X- and M-class flares are the most favourable configurations from which geoeffective CMEs originate. The analysis of related Solar Energetic Particle (SEP) events shows that 74% of the CMEs associated with major SEPs were geoeffective, i.e. they triggered a minor to intense geomagnetic storm ( K p  ≥ 5). Moreover, the SEP production is enhanced in the case of fast and interacting CMEs. In this work we present a first attempt at applying a Sun-to-Earth geoeffectiveness prediction scheme − based on 3D simulations and solar wind-geomagnetic activity coupling functions − to a statistical set of fast Earth-directed, potentially geoeffective halo CMEs. The results of the prediction scheme are promising and in good agreement with the actual data records for geomagnetic activity. However, we point out the need for future studies performing a fine-tuning of the prediction scheme, in particular in terms of the evaluation of the CME input parameters and the modelling of their internal magnetic structure.

Cord blood platelet rich plasma (CB-PRP) derivatives have been investigated as potential therapeutic agents for the treatment of diverse conditions including ocular surface disease and skin ulcers. We have developed processes for the formulation of several CB-PRP preparations, which have different composition and attributes. Here we describe the molecular characteristics of these preparations and we make recommendations as to their most appropriate clinical application based on functional and immunomodulatory profiles. We show that incubation of adult peripheral blood mononuclear cells (PBMCs) with all three preparations dramatically reduced the production of INFγ and the expression of NKG2D and CD107a in NK, NKT, and T cells thus diminishing their activation, we propose that the likely mechanism is the high levels of soluble NKG2D ligands present in plasma. Of the three preparations we investigated, CB platelet lysate (PL) and platelet releaseate (PR) have higher concentrations of trophic and pro-angiogenic factors, CB platelet poor plasma (PPP) has the lowest concentration of all analytes measured. Based on these finding we propose that CB-PR is the most suitable raw material for skin wound patches, while CB-PL and PPP can be used to prepare eye drops for severe ocular surface pathologies and inflammatory conditions such as corneal ulcers or severe dry eye disease, respectively.

Diseases and injuries that compromise the ocular surface cause considerable patient distress and have long term consequences for their quality of life. Treatment modalities that can address the delicate balance of tissue regeneration, inflammation and maintenance of corneal transparency are therefore needed. We have recently formulated two novel eye drops from placental tissues: cord blood platelet lysate (CBED) and amniotic membrane extract eye drops (AMED), which can be used to treat severe ocular disorders. Here we characterise these two preparations by measuring: (a) growth factors (GF) and cytokines composition, (b) promotion of human corneal epithelial cell (HCEC) growth and (c) effects on immune cells in a lymphocyte culture assay. Finally, their bioavailability was assayed in an ex vivo porcine corneal model. We show that both preparations contain GF and cytokines that were able to promote the in vitro growth of HCEC and support repair in an in vitro scratch test. When assessed in a lymphocyte culture, both favoured immune suppression reducing the cellular expression of NKG2D and CD107a as well as the production of interferon gamma (IFN-γ) in natural killer, NKT and T cells. Regarding bioavailability, CBED active molecules were found mainly in the pre-corneal fraction with some penetration into the corneal fraction, in an ex vivo model. In summary, both placental-derived allogeneic preparations, CBED and AMED, display regenerative and immunomodulatory capabilities. These results will help define mechanisms of action and the best indications and doses of each product for use in a particular patient and support the development of off-the-shelf therapies for ocular surface pathologies in which wound healing defects and inflammatory events are contributing factors.

Current magnetohydrodynamics (MHD) models largely rely on synoptic magnetograms, such as the ones produced by the Global Oscillation Network Group (GONG). Magnetograms are currently available mostly from the front side of the Sun, which significantly reduces the accuracy of MHD modeling. Extreme Ultraviolet (EUV) images can instead be obtained from other vantage points. To investigate the potential, we explore the possibility of using EUV information from the Atmospheric Imaging Assembly (AIA) to directly generate the input for the state‐of‐the‐art 3D MHD model European Heliospheric FORecasting Information Asset (EUHFORIA). Toward this goal, we develop a method called Transfer‐Solar‐GAN which combines a conditional generative adversarial network with a transfer learning approach to overcome training data set limitations. The source domain data set is constructed from multiple pairs of the central portion of co‐registered AIA and Helioseismic and Magnetic Imager (HMI) line of sight (LOS) full‐disk images, while the target domain is constructed from pairs of portions of AIA and GONG sine‐latitude synoptic maps that we call segments. We evaluate Transfer‐Solar‐GAN by comparing modeled and measured solar wind velocity and magnetic field density parameters at the L1 Lagrange point and along the Parker Solar Probe (PSP) trajectory which were determined with EUHFORIA using both empirical GONG and artificial‐intelligence (AI)‐synthetic synoptic magnetograms as inputs. Our results demonstrate that the Transfer‐Solar‐GAN model can provide the necessary information to run solar physics models by EUV information. Our proposed model is trained with only 528 paired image segments and enforces a reliable data division strategy.

Multipotent mesenchymal stromal cells (MSC) offer new therapeutic opportunities based on their ability to modulate an imbalanced immune system. Immunomodulatory potency is typically demonstrated in vitro by measuring the presence of surrogate markers (i.e., indoleamine-2,3-dioxygenase, IDO; tumor necrosis factor receptor type 1, TNFR1) and/or functional assays in co-cultures (i.e., inhibition of lymphoproliferation, polarization of macrophages). However, the biological variability of reagents used in the latter type of assays leads to unreliable and difficult to reproduce data therefore making cross-comparison between batches difficult, both at the intra- and inter-laboratory levels. Herein, we describe a set of experiments aiming at the definition and validation of reliable biological reagents as a first step towards standardization of a potency assay. This approach is based on the co-culture of Wharton’s jelly (WJ)-derived MSC and cryopreserved pooled peripheral blood mononuclear cells. Altogether, we successfully defined a robust and reproducible immunopotency assay based on previously described methods incorporating substantial improvements such as cryopreservation of multiple vials of pooled peripheral blood mononuclear cells (PBMC) from 5 individual donors that enable a number of tests with same reagents, also reducing waste of PBMC from individual donors and therefore contributing to a more efficient and ethical method to use substances of human origin (SoHO). The new methodology was successfully validated using 11 batches of clinical grade MSC,WJ. Methods described here contribute to minimize PBMC donor variability while reducing costs, streamlining assay setup and convenience and laying the foundations for harmonization of biological reagents usage in standardized immunopotency assays for MSC.Highlights• The use of pools of peripheral blood mononuclear cells (PBMCs) in potency assays contributes to robust and reproducible results, which is key in the assessment of mesenchymal stroma cells (MSC) potency for batch release.• Cryopreservation of PBMCs does not impact negatively on their activation and proliferation abilities.• Cryopreserved pools of PBMC constitutes convenient off-the-shelf reagents for potency assays.• Cryopreservation of pooled PBMCs from multiple donors is a way to reduce waste of donated PBMC and its associated costs, as well as reducing the impact of individual donor variability of substances of human origin (SoHO).

Photoconductive semiconductor switching (PCSS) devices have unique characteristics to address the growing need for electrically isolated, optically gated, picosecond-scale jitter devices capable of operating at high voltage, current, and frequency. The state of the art in material selection, doping, triggering, and system integration in PCSSs is presented. The material properties and doping considerations of GaN, GaAs, SiC, diamond, and β-Ga2O3 in the fabrication of PCSS devices are discussed. A review of the current understanding of the physics of the high-gain mode known as lock-on is presented.

Aims . Our goal is to develop and provide an open end-to-end (Sun to Earth) space weather modeling system, enabling to combine (“couple”) various space weather models in an integrated tool, with the models located either locally or geographically distributed, so as to better understand the challenges in creating such an integrated environment. Methods . The physics-based models are installed on different compute clusters and can be run interactively and remotely and that can be coupled over the internet, using open source “high-level architecture” software, to make complex modeling chains involving models from the Sun to the Earth. Visualization tools have been integrated as “models” that can be coupled to any other integrated model with compatible output. Results . The first operational version of the VSWMC is accessible via the SWE Portal and demonstrates its end-to-end simulation capability. Users interact via the front-end GUI and can interactively run complex coupled simulation models and view and retrieve the output, including standard visualizations, via the GUI. Hence, the VSWMC provides the capability to validate and compare model outputs.