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This study aims to evaluate the effect of autologous adipose-derived mesenchymal stem cells (AAD-MSC), with and without synthetic absorbable hydroxyapatite (HAP-91), on the bone regeneration in rabbits. Thirty-four female white New Zealand rabbits were submitted to a 10 mm distal diaphyseal radius ostectomy, divided into 3 experimental groups according to the treatment established. The bone gap was filled with 0.15 ml of a 0.9% saline solution containing two million AAD-MSC (G1), or AAD-MSC associated with HAP-91 (G2). The control group (CG) received only 0.15 ml of the 0.9% saline solution. Radiographs were made post-operatively, and after 15, 30, 45 and 90 days. Fifty percent of the samples were submitted to a histological examination at 45 days and the remaining ones at 90 days post-operatively. Radiographically, the periosteal reaction, bone callus volume and bone bridge quality were superior in G2 ( 0.05). Histologically, the bone repair was faster and more efficient in G1 at 45 days ( 0.05). In conclusion, AAD-MSC improved the regeneration on the experimentally induced bone defects in rabbits; however, the use of hydroxyapatite requires caution given the granulomatous reaction produced in the species.

Data quality of the tokamaks diagnostics is often a neglected topic. In literature it is rather rare to find considerations regarding the data quality received from the diagnostic systems’ sensors. The scope of the paper is to provide a discussion regarding systems’ construction and analysis in scope of implementation of data quality monitoring methods for a new generation of diagnostics. Mainly considerations are performed regarding the necessity of DQM (Data Quality Monitoring) implementation, functionality, performance and required system resources. The covered topics are related to basics of system construction including: system layout and construction blocks, data processing stages, signal processing modes, system construction with resource estimation in scope of DQM implementation. Based on the covered points, it is possible to plan the extra resources or specific construction, to provide reliable design with data quality monitoring features. The data quality monitoring aspect is especially important in the modern diagnostics working with a real-time feedback loop. Such approach could be especially interesting for the ITER-like projects, since the quality of the data may directly influence the behavior of the control systems during plasma phenomena. The work is based on experience in design work of various high performance diagnostic systems for plasma physics and high energy physics.

This contribution reviews an important example of current developments in diagnostic systems and data analysis tools aimed at improved understanding and control of transport processes in magnetically confined high temperature plasmas. The choice of tungsten for the plasma facing components of ITER and probably also DEMO means that impurity control in fusion plasmas is now a crucial challenge. Soft X-ray (SXR) diagnostic systems serve as a key sensor for experimental studies of plasma impurity transport with a clear prospective of its control via actuators based mainly on plasma heating systems. The SXR diagnostic systems typically feature high temporal resolution but limited spatial resolution due to access restrictions. In order to reconstruct the spatial distribution of the SXR radiation from line integrated measurements, appropriate tomographic methods have been developed and validated, while novel numerical methods relevant for real-time control have been proposed. Furthermore, in order to identify the main contributors to the SXR plasma radiation, at least partial control over the spectral sensitivity range of the detectors would be beneficial, which motivates for developments of novel SXR diagnostic methods. Last, but not least, semiconductor photosensitive elements cannot survive in harsh conditions of future fusion reactors due to radiation damage, which calls for development of radiation hard SXR detectors. Present research in this field is exemplified on recent results from tokamaks COMPASS, TORE SUPRA and the Joint European Torus JET. Further planning is outlined.

Valuable female cattle are continuously subject to follicular puncture (ovum pick-up - OPU). This technique is commonly used for in-vitro embryo production, but may result in ovarian lesion. Mesenchymal stem cells (MSC) ameliorate the function of injured tissues, but their use to treat ovarian lesions in cattle has not been established. We investigated whether a local injection of MSC would reduce the negative effects of repeated OPU under acute and chronic scenarios in bovines. First, we performed four OPU sessions and injected 2.5 × 10 6 MSCs immediately after the 4th OPU procedure (n = 5). The treated organs (right ovary) were compared to their saline-treated counterparts (left), and presented superior production of oocytes and embryos in the three following OPU sessions (P < 0.05). Then, cows with progressive fertility loss went through three OPU sessions. Animals received MSC, saline, or MSC + FSH in both ovaries after the first OPU. In the two following OPU sessions, the MSC and MSC + FSH - treated groups failed to present any significant alteration in the number of oocytes and embryos compared to saline-treated animals. Thus, MSC have beneficial effects on the fertility of OPU-lesioned cows, but not in cows with cystic ovarian disease and chronic ovarian lesions.

WEST (Tungsten Environment in Steady-State Tokamak) will be operating by the end of 2016 as a test bed for the ITER divertor components in long pulse operation. In this context, radiative cooling of highly ionized impurities like tungsten (W) sputtered from Plasma Facing Components (PFC) into the plasma core is a critical issue since even small impurity concentrations below 10-4 degrade significantly plasma performances and can lead to radiative collapse. In the plasma core, tungsten emission is dominant in the Soft X-ray (SXR) range 0.1 keV -- 15 keV with complex contributions from line transition, radiative recombination and Bremsstrahlung emission.This paper presents the recent development of a synthetic SXR diagnostic using GEM (Gas Electron Multiplier) detectors. This diagnostic will be used on WEST for W transport studies and will be equipped with two new GEM based poloidal cameras allowing 2D tomographic reconstructions with spectral resolution in energy bands. Thus once GEM response to plasma emissivity is characterized thanks to synthetic diagnostic, it offers new possibilities to disentangle the different SXR contributions in harsh fusion environments like e.g. WEST or ITER with respect to conventional semiconductor diodes working in current mode. Emitted SXR spectrum from the plasma is modelled thanks to ADAS database from given WEST scenario. The synthetic diagnostic includes Lines of Sight (LoS) etendues of the two cameras as well as probability of photoabsorption through filters, photoionization in the detection gas mixture (Ar-CO2), and transport of electron avalanches in the gas through GEM foils as computed with Magboltz. Local SXR emissivity is then retrieved from tomographic inversion using a Minimum Fisher Information (MFI) algorithm.

Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHCT) and is a major cause of morbidity and mortality. Systemic steroid therapy is the first-line treatment for aGVHD, although about half of patients will become refractory to treatment. As the number of patients undergoing alloHCT increases, developing safe and effective treatments for aGVHD will become increasingly important, especially for those whose disease becomes refractory to systemic steroid therapy. This paper reviews current treatment options for patients with steroid-refractory aGVHD and discusses data from recently published clinical studies to outline emerging therapeutic strategies.

U1 interference (U1i) RNAs can be designed to correct splicing defects and target pathogenic RNA, such as HIV-1 RNA. In this study, we show that U1i RNAs that enhance HIV-1 RNA splicing are more effective at inhibiting HIV-1 production compared to top U1i RNAs that inhibit polyadenylation of HIV-1 RNA. A U1i RNA was also identified targeting a site upstream of the first splice acceptor site in the Gag coding region that was effective at inhibiting HIV-1 production. U1-T6, which enhanced HIV-1 RNA splicing, was superior to an antiviral short hairpin RNA (shRNA) currently in clinical trials. To increase specificity, the recognition domain of U1-T6 was elongated by 3–6 nt. The elongated molecules inhibited HIV-1 production from different HIV-1 strains, including one with a mismatch in the target site. These results suggest that lengthening the recognition domain can enhance the specificity of U1i RNAs for their intended target sites while at the same time allowing them to tolerate single mismatch mutations. Overall, our results demonstrate that U1-T6 with an elongated recognition domain inhibits HIV-1 production and has both the efficacy and specificity to be a promising candidate for HIV-1 gene therapy.

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.

Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group ( P  = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group ( P  = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679.