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Abstract We report on the measurements of the spectra of gamma radiation generated by 855 MeV electrons in bent silicon and germanium crystals at MAMI (MAinzer MIkrotron). The crystals were 15 $$\upmu \text {m}$$ μ m thick along the beam direction to ensure high deflection efficiency. Their (111) crystalline planes were bent by means of a piezo-actuated mechanical holder, which allowed to remotely change the crystal curvature. In such a way it was possible to investigate the radiation emitted under planar channeling and volume reflection as a function of the curvature of the crystalline planes. We showed that, using volume reflection, intense gamma radiation can be produced – with intensity comparable to that obtained in channeling but with higher angular acceptance. We studied the trade-off between radiation intensity and angular acceptance at different values of the crystal curvature. The measurements of radiation spectra have been carried out for the first time in bent germanium crystals. In particular, the intensity of radiation in the germanium crystal is higher than in the silicon one due to the higher atomic number, which is important for the development of the X-ray and gamma radiation sources based on higher-Z deformed crystals, such as crystalline undulators.

Abstract We observed reduction of multiple Coulomb scattering of 855 MeV electrons within a Si crystalline plate w.r.t. an amorphous plate with the same mass thickness. The reduction owed to complete or partial suppression of the coherent part of multiple scattering in a crystal vs crystal orientation with the beam. Experimental data were collected at Mainz Mikrotron and critically compared to theoretical predictions and Monte Carlo simulations. Our results highlighted maximal 7% reduction of the r.m.s. scattering angle at certain beam alignment with the [100] crystal axes. However, partial reduction was recorded over a wide range of alignment of the electron beam with the crystal up to 15$$^{\circ }$$ ∘ . This evidence may be relevant to refine the modelling of multiple scattering in crystals for currently used software, which is interesting for detectors in nuclear, medical, high energy physics.

Abstract Beam steering performance of bent silicon crystals irradiated with high-intensity and high-energy protons has been studied. In particular, crystals of the type used for collimation and extraction purposes in the Large Hadron Collider and the Super Proton Synchrotron at CERN have been irradiated at the HiRadMat CERN facility with $$2.5 \times 10^{13}$$ 2.5×1013 440 GeV/c protons, with a pulse length of 7.2 $$\upmu $$ μ s. The purpose is to study possible changes in bending angle and channeling efficiency due to thermo-mechanical stresses in case of accidental irradiation during accelerator operations. A comparison between measurements performed before and after the irradiation does not show any appreciable performance reduction in either crystal.

Strong reduction of multiple scattering for channeled particles has been observed in an experiment on the deflection of a 180 GeV/c π+-meson beam by bent silicon crystals. The RMS deflections due to multiple scattering for the channeled particles were about six times smaller than for non-channeled ones. It was shown that the approach suggested recently for the description of multiple scattering for channeled particles using the experimental data for random crystal orientations gives fair agreement with the experiment. Keywords: Crystal, Channeling, Multiple scattering, Dechanneling, Beam deflection

Abstract Charged particle beams can be manipulated by exploiting the channeling phenomenon in bent crystals. Two plate-like crystals, bent by mechanical holders, were manufactured and characterised for such purpose at the Sensor and Semiconductor Laboratory in Ferrara, Italy. An anticlastic curvature was obtained for these crystals, achieving a steering angle of the order of 1 mrad, which is about 20 times larger than the values currently achieved for the bent crystals used in the LHC for collimation experiments. Finally, a Geant4 simulation was performed to study the channeling efficiency for beam deflection with 400 GeV/c and 7 TeV/c proton beams. Such crystals represent technological progress in the development of bent crystals for highly energetic charged particle beams. Indeed, they are designed to impart an angular kick to a 7 TeV/c proton beam with unprecedented high efficiency. Therefore, this study demonstrates the possibility of realizing bent crystals suitable for beam extraction in high-energy hadron accelerators, such as LHC or at the future FCC. A further series of studies should be conducted to evaluate the channeling efficiency and the deflection angle of the realized crystals via a charged proton beam.

Abstract Inelastic nuclear interaction probability of 400 GeV/c protons interacting with bent silicon crystals was investigated, in particular for both types of crystals installed at the CERN Large Hadron Collider for beam collimation purposes. In comparison to amorphous scattering interaction, in planar channeling this probability is $$\sim 36\%$$ ∼36% for the quasi-mosaic type (planes (111)), and $$\sim 27\%$$ ∼27% for the strip type (planes (110)). Moreover, the absolute inelastic nuclear interaction probability in the axial channeling orientation, along the $$\langle 110\rangle $$ ⟨110⟩ axis, was estimated for the first time, finding a value of $$0.6\%$$ 0.6% for a crystal 2 mm long along the beam direction, with a bending angle of 55 $$\upmu $$ μ rad. This value is more than two times lower with respect to the planar channeling orientation of the same crystal, and increases with the vertical angular misalignment. Finally, the correlation between the inelastic nuclear interaction probability in the planar channeling and the silicon crystal curvature is reported.

Abstract We propose a unique program of measurements of electric and magnetic dipole moments of charm, beauty and strange charged baryons at the LHC, based on the phenomenon of spin precession of channeled particles in bent crystals. Studies of crystal channeling and spin precession of positively- and negatively-charged particles are presented, along with feasibility studies and expected sensitivities for the proposed experiment using a layout based on the LHCb detector.

Abstract We report the observation of the steering of 855 MeV electrons by bent silicon and germanium crystals at the MAinzer MIkrotron. Crystals with 15 $$\upmu $$ μ m of length, bent along (111) planes, were exploited to investigate orientational coherent effects. By using a piezo-actuated mechanical holder, which allowed to remotely change the crystal curvature, it was possible to study the steering capability of planar channeling and volume reflection vs. the curvature radius and the atomic number, Z. For silicon, the channeling efficiency exceeds 35%, a record for negatively charged particles. This was possible due to the realization of a crystal with a thickness of the order of the dechanneling length. On the other hand, for germanium the efficiency is slightly below 10% due to the stronger contribution of multiple scattering for a higher-Z material. Nevertheless this is the first evidence of negative beam steering by planar channeling in a Ge crystal. Having determined for the first time the dechanneling length, one may design a Ge crystal based on such knowledge providing nearly the same channeling efficiency of silicon. The presented results are relevant for crystal-based beam manipulation as well as for the generation of e.m. radiation in bent and periodically bent crystals.

In this Erratum, an improved simulation of the channeling efficiency of protons and antiprotons as a function of the particle momentum is shown in for different configurations

Experimental results and simulation models show that crystals might play a relevant role for the development of new generations of high-energy and high-intensity particle accelerators and might disclose innovative possibilities at existing ones. In this paper we describe the most advanced manufacturing techniques of crystals suitable for operations at ultrahigh energy and ultrahigh intensity particle accelerators, reporting as an example of potential application the collimation of the particle beams circulating in the Large Hadron Collider at CERN, which will be upgraded through the addition of bent crystals in the frame of the High Luminosity Large Hadron Collider project.

A deflection efficiency of about 61% was observed for 400 GeV/c protons due to channeling, most strongly along the 〈110〉 axis of a bent silicon crystal. It is comparable with the deflection efficiency in planar channeling and considerably larger than in the case of the 〈111〉 axis. The measured probability of inelastic nuclear interactions of protons in channeling along the 〈110〉 axis is only about 10% of its amorphous level whereas in channeling along the (110) planes it is about 25%. High efficiency deflection and small beam losses make this axial orientation of a silicon crystal a useful tool for the beam steering of high energy charged particles.

Two high-accuracy goniometers equipped with two bent silicon crystals were installed in the betatron cleaning insertion of the CERN Large Hadron Collider (LHC) during its long shutdown. First beam tests were recently performed at the LHC with 450 GeV/c and 6500 GeV/c stored proton beams to investigate the feasibility of beam halo collimation assisted by bent crystals. For the first time channeling of 6500 GeV/c protons was observed in a particle accelerator. A strong reduction of beam losses due to nuclear inelastic interactions in the aligned crystal in comparison with its amorphous orientation was detected. The loss reduction value was about 24. Thus, the results show that deflection of particles by a bent crystal due to channeling is effective for this record particle energy.

In ideal two-stage collimation systems, the secondary collimator–absorber should have its length sufficient to exclude practically the exit of halo particles with large impact parameters. In the UA9 experiments on the crystal assisted collimation of the SPS beam a 60 cm long tungsten bar is used as a secondary collimator–absorber which is insufficient for the full absorption of the halo protons. Multi-turn simulation studies of the collimation allowed to select the position for the beam loss monitor downstream the collimation area where the contribution of particles deflected by the crystal in channeling regime but emerging from the secondary collimator–absorber is considerably reduced. This allowed observation of a strong leakage reduction of halo protons from the SPS beam collimation area, thereby approaching the case with an ideal absorber.

Deflection of 400 GeV/c protons by a short bent silicon crystal was studied at the CERN SPS. It was shown that the dechanneling probability increases while the dechanneling length decreases with an increase of incident angles of particles relative to the crystal planes. The observation of the dechanneling length reduction provides evidence of the particle population increase at the top levels of transverse energies in the potential well of the planar channels. Keywords: Crystal, Channeling, Beam, Deflection

We present a quantitative experimental analysis of the radiation emission of 12.6 GeV electrons moving along and across the (111) planes of a strongly bent silicon crystal with a bending radius of 0.15 m. We have measured the radiation emitted during volume reflection, which has shown to strongly enhance the emission of low-energy photons, and a convincing agreement between simulations and experimental data is found.

This paper is devoted to an experimental study of focusing and defocusing positively charged particle beams with the help of specially bent single crystals. Four crystals have been fabricated for this purpose. The studies have been performed at the CERN SPS in 400 GeV/c proton and 180 GeV/c pion beams. The results of measurements of beam envelopes are presented. The rms size of the horizontal profile at the focus was 5–8 times smaller than at the exit of the crystals. The measured focal lengths were 4–21 m. The results of measurements are in good agreement with calculations. Possible applications of focusing crystals in present and future high energy accelerators are discussed.

We present the experimental data and analysis of experiments conducted at SLAC National Accelerator Laboratory investigating the processes of channeling, volume-reflection and volume-capture along the (111) plane in a strongly bent quasimosaic silicon crystal. These phenomena were investigated at 5 energies: 3.35, 4.2, 6.3, 10.5, and 14.0 GeV with a crystal with bending radius of 0.15 m, corresponding to curvatures of 0.053, 0.066, 0.099, 0.16, and 0.22 times the critical curvature, respectively. Based on the parameters of fitting functions we have extracted important parameters describing the channeling process such as the dechanneling length, the angle of volume reflection, the surface transmission, and the widths of the distribution of channeled particles parallel and orthogonal to the plane.

In fusion, the validation of turbulent transport models is undertaken with the goals of making basic physics discoveries as well as for development of new predictive models to improve the operation and enhance the performance of existing and future fusion reactors. A fusion industry is just beginning to emerge globally. Like fission, validation in fusion energy research is a vibrant research area, but unlike fusion, a fission industry exists. The fission power industry motivates validation efforts, often performed at universities with small-scale experiments and advanced models and simulations developed in-house. Because fission research spans basic physics and applications, and addresses near-term and long-term industry interests, validation is thriving. This perspective article describes the validation of turbulent transport models in both fusion research and fission research, draws parallels between the validation methods and techniques used in two areas of the fields, and presents an outlook for thriving university fusion and fission research programs underpinned by a virtual cycle of basic and applied research that supports industry needs as well as tackling intellectual grand challenges.

We present a source solution for the tsunami generated by the Mw 6.6 earthquake that occurred on 2 May 2020, about 80 km offshore south of Crete, in the Cretan Passage, on the shallow portion of the Hellenic Arc subduction zone (HASZ). The tide gauges recorded this local tsunami on the southern coast of Crete and Kasos island. We used Crete tsunami observations to constrain the geometry and orientation of the causative fault, the rupture mechanism, and the slip amount. We first modelled an ensemble of synthetic tsunami waveforms at the tide gauge locations, produced for a range of earthquake parameter values as constrained by some of the available moment tensor solutions. We allow for both a splay and a back-thrust fault, corresponding to the two nodal planes of the moment tensor solution. We then measured the misfit between the synthetic and the Ierapetra observed marigram for each source parameter set. Our results identify the shallow, steeply dipping back-thrust fault as the one producing the lowest misfit to the tsunami data. However, a rupture on a lower angle fault, possibly a splay fault, with a sinistral component due to the oblique convergence on this segment of the HASZ, cannot be completely ruled out. This earthquake reminds us that the uncertainty regarding potential earthquake mechanisms at a specific location remains quite significant. In this case, for example, it is not possible to anticipate if the next event will be one occurring on the subduction interface, on a splay fault, or on a back-thrust, which seems the most likely for the event under investigation. This circumstance bears important consequences because back-thrust and splay faults might enhance the tsunamigenic potential with respect to the subduction interface due to their steeper dip. Then, these results are relevant for tsunami forecasting in the framework of both the long-term hazard assessment and the early warning systems.

This is a unique case of retinoschisis as an ocular manifestation of brucellosis. A 38-year-old male presented with recurrent episodes of bilateral eye redness, predominately in his left eye. His visual acuity was not affected, and he did not report any other symptoms. On slit lamp examination, binocular Koeppe nodules of the iris and cells in the left anterior chamber were observed. Fundoscopy followed by meticulous multimodal imaging confirmed left inferior retinoschisis. The patient was diagnosed with panuveitis, and a series of laboratory examinations revealed positive anti-IgM Brucella antibodies. Ocular brucellosis can cause variable, atypical, and serious presentations, hence, early diagnosis is paramount to avoid complications., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Chondroitin sulfate (ChS), chitosan (Chi), and fish gelatin (FG), which are byproducts of a fish-treatment small enterprise, were incorporated with glycerol (Gly) to obtain dense hydrogel membranes with reduced brittleness, candidates for dressing in wound healing applications. The mechanical properties of all samples were studied via Dynamic Mechanical Analysis (DMA) and tensile tests while their internal structure was characterized using Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray Diffraction (XRD) instruments. Their surface morphology was analyzed by ThermoGravimetric Analysis (TGA) method, while their water permeability was estimated via Water Vapor Transmission Rate (WVTR) measurements. Wettability and degradation rate measurements were also carried out. Characterization results indicated that secondary interactions between the natural polymers and the plasticizer create the hydrogel membranes. The samples were amorphous due to the high concentration of plasticizer and the amorphous nature of the natural polymers. The integration of ChS led to decreased decomposition temperature in comparison with the glycerol-free sample, and all the materials had dense structures. Finally, the in vitro endothelial cell attachment studies indicate that the hydrogel membranes successfully support the attachment and survival of primary on the hydrogel membranes and could be appropriate for external application in wound healing applications as dressings.

Human pluripotent stem cell culture conditions are constantly being optimized, thus providing insight to the environmental cues that affect cell choices. A wide variety of media, coating materials, and substrates is now available for use, serving different scientific needs. Factors such as material stiffness, roughness, and topography are being recognized to contribute or even direct the acquisition of specific phenotypes. Here, we describe the use of patterned silicon substrates coated with Matrigel for the propagation and differentiation of human pluripotent stem cells., (© 2021. Springer Science+Business Media, LLC.)

The human brain carries out complex tasks and higher functions and is crucial for organismal survival, as it senses both intrinsic and extrinsic environments. Proper brain development relies on the orchestrated development of different precursor cells, which will give rise to the plethora of mature brain cell-types. Within this process, neuronal cells develop closely to and in coordination with vascular cells (endothelial cells (ECs), pericytes) in a bilateral communication process that relies on neuronal activity, attractive or repulsive guidance cues for both cell types and on tight-regulation of gene expression. Translational control is a master regulator of the gene-expression pathway and in particular for neuronal and ECs, it can be localized in developmentally relevant (axon growth cone, endothelial tip cell) and mature compartments (synapses, axons). Herein, we will review mechanisms of translational control relevant to brain development in neurons and ECs in health and disease., (© 2021 The Authors.)

Ligand-receptor complexes formed at the plasma membrane are internalised via various endocytic pathways that influence the ultimate signalling output by regulating the selection of interaction partners by the complex along the trafficking route. We report that, in differentiated cells, activin A-receptor complexes are internalised via clathrin-mediated endocytosis (CME) and macropinocytosis (MP), whereas in human embryonic stem cells (hESCs) internalisation occurs via CME. We further show that hESCs are devoid of MP, which becomes functional upon differentiation towards endothelial cells through mesoderm mediators. Our results reveal, for the first time, that MP is an internalisation route for activin A in differentiated cells, and that MP is not active in hESCs and is induced as cells differentiate., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

In this study, we use non-linear imaging microscopy to characterize the structural properties of porous collagen-GAG scaffolds (CGS) seeded with human umbilical vein endothelial cells (HUVECs), as well as human mesenchymal stem cells (hMSCs), a co-culture previously reported to form vessel-like structures inside CGS. The evolution of the resulting tissue construct was monitored over 10 days via simultaneous two- and three-photon excited fluorescence microscopy. Time-lapsed 2- and 3-photon excited fluorescence imaging was utilized to monitor the temporal evolution of the vascular-like structures up to 100 µm inside the scaffold up to 10 days post-seeding. 3D polarization-dependent second harmonic generation (PSHG) was utilized to monitor collagen-based scaffold remodeling and determine collagen fibril orientation up to 200 µm inside the scaffold. We demonstrate that polarization-dependent second harmonic generation can provide a novel way to quantify the reorganization of the collagen architecture in CGS simultaneously with key biomechanical interactions between seeded cells and CGS that regulate the formation of vessel-like structures inside 3D tissue constructs. A comparison between samples at different days in vitro revealed that gradually, the scaffolds developed an orthogonal net-like architecture, previously found in real skin., Competing Interests: The data that support the findings of this study are available from the corresponding author upon reasonable request., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Purpose: To investigate the possible association of the matrix metalloproteinase 2 (MMP2)-1306C/T polymorphism with the risk of ischemic retinal vein occlusion (iRVO)., Methods: A total of 69 patients with RVO were enrolled in this study (43 with non-iRVO and 26 with iRVO). All subjects were screened for hypertension, diabetes mellitus, hyperlipidemia, history of stroke, anticoagulant medication, smoking status and glaucoma. The genotyping of MMP2-1306C/T polymorphism was performed using PCR-RFLP-based methods., Results: MMP2-1306C/T T allele carriers (CT+TT) were statistically significant associated with a higher risk of iRVO compared to CC genotype in the overall RVO group (odds ratio = 3.91, p = 0.015, 95% confidence interval:1.30-11.79). Analysis, following stratification by age revealed that T allele carriers had a statistically significant increased risk of iRVO compared to C allele carriers only in RVO patients <75 years old., Conclusion: Our results demonstrated that MMP2-1306C/T polymorphism is a likely predisposing factor for iRVO in patients <75 years old. This is the first study attempting association of a gene polymorphism with the prevalence of iRVO., (Copyright © 2020 IMSS. Published by Elsevier Inc. All rights reserved.)

Background: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries., Methods: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs)., Findings: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505)., Interpretation: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care., Competing Interests: Competing interests: Dr. James reports grants from Sanofi Pasteur, outside the submitted work. Dr. Driscoll reports grants from World Health Organization, during the conduct of the study. Dr. Ivers reports grants from National Health and Medical Research Council of Australia, during the conduct of the study. Dr. Jozwiak reports personal fees from TEVA, personal fees from ALAB, personal fees from BOEHRINGER INGELHEIM, personal fees from SYNEXUS, non-financial support from SERVIER, non-financial support from MICROLIFE, non-financial support from MEDICOVER, outside the submitted work. Dr. Rakovac reports grants from World Health Organization, during the conduct of the study. Dr Shariful Islam is funded by National Heart Foundation of Australia and Institute for Physical Activity and Nutrition, Deakin University. Dr. Sheikh reports grants from Health Data Research UK, outside the submitted work. Dr. Singh reports personal fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Trio health, Medscape, WebMD, Clinical Care options, Clearview healthcare partners, Putnam associates, Spherix, Practice Point communications, the National Institutes of Health and the American College of Rheumatology, and Speaker’s bureau of Simply Speaking, owns stock options in Amarin pharmaceuticals and Viking pharmaceuticals, serves on the steering committee of OMERACT, an international organization that develops measures for clinical trials and receives arm’s length funding from 12 pharmaceutical companies, serves on the FDA Arthritis Advisory Committee, is a member of the Veterans Affairs Rheumatology Field Advisory Committee, and is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis, outside the submitted work. Dr. Stein reports personal fees from Lundbeck, personal fees from Sun, outside the submitted work. Dr. Degenhardt reports grants from Indivior, Seqirus, Reckitt Benckiser, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Diffusion is a limiting factor in regenerating large tissues (100-200 μm) due to reduced nutrient supply and waste removal leading to low viability of the regenerating cells as neovascularization of the implant by the host is a slow process. Thus, generating prevascularized tissue engineered constructs, in which endothelial (ECs) and mural (MCs) cells, such as smooth muscle cells (SMCs), and pericytes (PCs), are preassembled into functional in vitro vessels capable of rapidly connecting to the host vasculature could overcome this obstacle. Toward this purpose, using feeder-free and low serum conditions, we developed a simple, efficient and rapid in vitro approach to induce the differentiation of human pluripotent stem cells-hPSCs (human embryonic stem cells and human induced pluripotent stem cells) to defined SMC populations (contractile and synthetic hPSC-SMCs) by extensively characterizing the cellular phenotype (expression of CD44, CD73, CD105, NG2, PDGFRβ, and contractile proteins) and function of hPSC-SMCs. The latter were phenotypically and functionally stable for at least 8 passages, and could stabilize vessel formation and inhibit vessel network regression, when co-cultured with ECs in vitro . Subsequently, using a methylcellulose-based hydrogel system, we generated spheroids consisting of EC/hPSC-SMC (vascular organoids), which were extensively phenotypically characterized. Moreover, the vascular organoids served as focal starting points for the sprouting of capillary-like structures in vitro , whereas their delivery in vivo led to rapid generation of a complex functional vascular network. Finally, we investigated the vascularization potential of these vascular organoids, when embedded in hydrogels composed of defined extracellular components (collagen/fibrinogen/fibronectin) that can be used as scaffolds in tissue engineering applications. In summary, we developed a robust method for the generation of defined SMC phenotypes from hPSCs. Fabrication of vascularized tissue constructs using hPSC-SMC/EC vascular organoids embedded in chemically defined matrices is a significant step forward in tissue engineering and regenerative medicine., (Copyright © 2020 Markou, Kouroupis, Badounas, Katsouras, Kyrkou, Fotsis, Murphy and Bagli.)

Purpose: To compare prospectively intravitreal ranibizumab treatment and pars plana vitrectomy (PPV) in patients with recurrent vitreous haemorrhage (VH) due to proliferative diabetic retinopathy (PDR), who were previously treated with PPV., Methods: Participants in this prospective study were 37 patients (37 eyes) with PDR, previously treated with PPV. All patients presented recurrent VH and were treated with either ranibizumab (n = 18) or PPV (n = 19). All participants were examined at week 2 post-treatment and every month thereafter for 1 year. Main outcomes were the need of PPV, the rate of recurrence of VH and the change in visual acuity by the end of the 12-month follow-up., Results: At month 12, there was statistically significant improvement in visual acuity in both groups compared to baseline, but the two groups did not differ regarding the change in visual acuity. In ranibizumab group, two patients presented recurrent VH during the follow-up and one patient needed PPV to clear the VH by month 12. In PPV group, two patients had mild recurrent VH, which cleared itself. No statistically significant difference was noticed regarding the rate of recurrent VH and the need of PPV between the two groups., Conclusion: Intravitreal ranibizumab seems to be a safe and effective treatment alternative in patients with recurrent VH secondary to PDR, who had been previously treated with PPV.

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data., Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning., Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence., Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs)., Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

Purpose: To investigate possible associations of single-nucleotide polymorphisms (SNPs) from five genes with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO)., Methods: A total of 69 patients with retinal vein occlusion-RVO (24 with BRVO and 45 with CRVO), and 82 controls, were enrolled in this study. All subjects were screened for hypertension, diabetes mellitus, hyperlipidemia, glaucoma, anticoagulant medication, smoking status and history of stroke. The genotyping of AGTR1-A1166C, adiponectin + 276 G/T, MMP2-1306C/T, Gpla/lla-C807T/G873A and VKORC1-G1639A polymorphisms was performed using restriction fragment length polymorphism or allele-specific polymerase chain reaction., Results: The percentage of the AGTR1-A1166C C allele carriers and Gpla/lla-C807T/G873A T/A carriers was significantly higher in the CRVO patients than in the controls (P = 0.00001 and P = 0.0004, respectively). At the multiple logistic regression analysis, the AGTR1-A1166C C allele carrier status and the Gpla/lla-C807T/G873A T/A allele carrier status were found to be associated with an increased risk of CRVO. Moreover, adiponectin + 276 G/T T allele carriers had a significantly increased risk of RVO in subjects ≥ 75 years old. There was no significant difference between the BRVO patients and controls concerning the genotype or the allele frequency distributions of these SNPs. The genotype distributions or allelic frequencies of the other evaluated polymorphisms did not significantly differ between the patients with RVO and the control subjects., Conclusions: AGTR1 A1166C and Gpla/lla C807T/G873A polymorphisms are likely to be risk factors for CRVO. Adiponectin + 276 G/T SNP is likely to predispose to RVO in older subjects.

The interaction rate of a charged particle beam with the atomic nuclei of a target varies significantly if the target has a crystalline structure. In particular, under specific orientations of the target with respect to the incident beam, the probability of inelastic interaction with nuclei can be enhanced with respect to the unaligned case. This effect, which can be named antichanneling, can be advantageously used in the cases where the interaction between beam and target has to be maximized. Here we propose to use antichanneling to increase the radioisotope production yield via cyclotron. A dedicated set of experimental measurements was carried out at the INFN Legnaro Laboratories with the AN2000 and CN accelerators to prove the existence of the antichanneling effect. The variation of the interaction yield at hundreds of keV to MeV energies was observed by means of sapphire and indium phosphide crystals, achieving an enhancement of the interaction rate up to 73% and 25%, respectively. Such a result may pave the way to the development of a novel type of nozzle for the existing cyclotrons, which can exploit crystalline materials as targets for radioisotope production, especially to enhance the production rate for expensive prime materials with minor upgrades of the current instrumentation.

Background/aim: Fuchs' endothelial corneal dystrophy (FECD) is a hereditary, progressive, bilateral, and irreversible disorder of the corneal endothelium. The purpose of this study was to develop a novel, accurate and high-throughput real-time polymerase chain reaction (PCR) method and melting-curve analysis in order to genotype the rs613872 polymorphism in the transcription factor 4 (TCF4) gene and to implement it on a well-ascertained sample of 22 Greek FECD patients and 58 healthy individuals, age- and sex-matched., Patients and Methods: DNA was extracted from blood samples, which were screened with the DNA sequencing method in order to detect the g.31753T>G/p.L450W (rs8035192) and g.31767C>A/p.Q455K (rs8035191) mutations in a COL8A2 genomic region., Results: TCF4 risk G allele frequency increased to 48% in FECD patients compared to 17% in healthy-subjects [OR=4.82 (95% CI=1.98-11.73)]. No p.L450W and p.Q455K COL8A2 gene mutations were detected., Conclusion: We confirmed that rs613872 in the TCF4 gene is strongly and statistically associated with late-onset FECD in a Greek population., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We measured a considerable increase of the emitted radiation by 120  GeV/c electrons in an axially oriented lead tungstate scintillator crystal, if compared to the case in which the sample was not aligned with the beam direction. This enhancement resulted from the interaction of particles with the strong crystalline electromagnetic field. The data collected at the external lines of the CERN Super Proton Synchrotron were critically compared to Monte Carlo simulations based on the Baier-Katkov quasiclassical method, highlighting a reduction of the scintillator radiation length by a factor of 5 in the case of beam alignment with the [001] crystal axes. The observed effect opens the way to the realization of compact electromagnetic calorimeters or detectors based on oriented scintillator crystals in which the amount of material can be strongly reduced with respect to the state of the art. These devices could have relevant applications in fixed-target experiments, as well as in satellite-borne γ telescopes.

Background Cardiac repair strategies are being evaluated for myocardial infarctions, but the safety issues regarding their arrhythmogenic potential remain unresolved. By utilizing the in-vivo rat model, we have examined the medium-term electrophysiologic effects of a biomaterial scaffold that has been cellularized with spheroids of human adipose tissue, derived from mesenchymal stem cells and umbilical vein endothelial cells. Methods Mesenchymal stem cells, which exhibit adequate differentiation capacity, were co-cultured with umbilical vein endothelial cells and were seeded on an alginate based scaffold. After in-vitro characterization, the cellularized scaffold was implanted in (n=15) adult Wistar rats 15 min post ligation of the left coronary artery, with an equal number of animals serving as controls. Two weeks thereafter, monophasic action potentials were recorded and activation-mapping was performed with a multi-electrode array. An arrhythmia score for inducible ventricular tachyarrhythmias was calculated after programmed electrical stimulation. Results The arrhythmia score was comparable between the treated animals and controls. No differences were detected in the local conduction at the infarct border and in the voltage rise in monophasic action potential recordings. Treatment did not affect the duration of local repolarization, but tended to enhance its dispersion. Conclusions The fabricated bi-culture cellularized scaffold displayed favorable properties after in-vitro characterization. Medium-term electrophysiologic assessment after implantation in the infarcted rat myocardium revealed low arrhythmogenic potential, but the long-term effects on repolarization dispersion will require further investigation., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To assess macro- and microstructural brain changes in patients with pseudoexfoliation syndrome (PXS)., Materials and Methods: Comprehensive ophthalmic examination and brain MRI were conducted on 20 patients with PXS without glaucoma (aged 62.75 ± 0.4 years) and 20 controls (aged 62 ± 0.6 years). White matter (WM) integrity was evaluated on FLAIR and single-shot multisection SE-EPI diffusion tensor imaging (DTI) sequences. The presence and the number of white matter hyperintensities (WMHIs) on FLAIR images was compared between all patients and control subjects. Microstructural WM changes on DTI was evaluated using Tract-based spatial statistics (TBSS). DTI metrics of the optic tracts were assessed by the region-of-interest (ROI) method., Results: A significantly higher number of WMHIs was found in the patients with PXS than in the control subjects (P ≤ 0.002). On DTI the patients showed bilateral increase in the mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) values in the anterior thalamic radiation, the inferior fronto-occipital fasciculus, the superior longitudinal fasciculus, the inferior longitudinal fasciculus and the forceps minor. TBSS revealed no significant difference in fractional anisotropy (FA) values, but ROIs analysis of the optic tracts revealed decreased FA values in the patients., Conclusion: MRI in patients with PXS detects abnormalities in the brain and the optic tracts at a subclinical stage. Early detection of microstructural changes could be useful to guide appropriate treatment to impede the disease process., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Inelastic nuclear interaction probability of 400 GeV/c protons interacting with bent silicon crystals was investigated, in particular for both types of crystals installed at the CERN Large Hadron Collider for beam collimation purposes. In comparison to amorphous scattering interaction, in planar channeling this probability is ∼ 36 % for the quasi-mosaic type (planes (111)), and ∼ 27 % for the strip type (planes (110)). Moreover, the absolute inelastic nuclear interaction probability in the axial channeling orientation, along the ⟨ 110 ⟩ axis, was estimated for the first time, finding a value of 0.6 % for a crystal 2 mm long along the beam direction, with a bending angle of 55 μ rad. This value is more than two times lower with respect to the planar channeling orientation of the same crystal, and increases with the vertical angular misalignment. Finally, the correlation between the inelastic nuclear interaction probability in the planar channeling and the silicon crystal curvature is reported.

Charged particle beams can be manipulated by exploiting the channeling phenomenon in bent crystals. Two plate-like crystals, bent by mechanical holders, were manufactured and characterised for such purpose at the Sensor and Semiconductor Laboratory in Ferrara, Italy. An anticlastic curvature was obtained for these crystals, achieving a steering angle of the order of 1 mrad, which is about 20 times larger than the values currently achieved for the bent crystals used in the LHC for collimation experiments. Finally, a Geant4 simulation was performed to study the channeling efficiency for beam deflection with 400 GeV/c and 7 TeV/c proton beams. Such crystals represent technological progress in the development of bent crystals for highly energetic charged particle beams. Indeed, they are designed to impart an angular kick to a 7 TeV/c proton beam with unprecedented high efficiency. Therefore, this study demonstrates the possibility of realizing bent crystals suitable for beam extraction in high-energy hadron accelerators, such as LHC or at the future FCC. A further series of studies should be conducted to evaluate the channeling efficiency and the deflection angle of the realized crystals via a charged proton beam.

Mechanical stress exerts a substantial role on skeletal-cell renewal systems, whereas accumulating evidence suggests that epigenetic mechanisms induce changes and differential gene expression. Although the underlying mechanisms remain to be fully elucidated, our study suggests that the influence of the long term mechanical stimulation elicits epigenetic modifications controlling osteogenic differentiation of human adipose tissue multipotential stromal cells (hAT-MSCs) and contributes to an accelerating in vitro osteogenesis. GNAS imprinting gene acts as a critical regulator of osteoblast differentiation and is implicated in human genetic disorders with pathological formation of ectopic-skeletal bone. Investigating a wide variety of stimuli, we showed that daily mechanical stretch on hAT-MSCs of 7th and 15th days' intervals induced a significant down-regulation in DNA methylation status of critical CpG sites of NESP and GNASXL isoforms, accompanied by up-regulation of the corresponding gene transcripts, and osteogenic differentiation earlier in culture. Importantly, methylation analysis of differentiating bone marrow-derived MSCs revealed similar methylation patterns. Bioinformatic analysis further showed that all CpG islands exhibiting significant methylation alterations encompassed transcriptional repressor CTCF binding sites. We hereby emphasize the need to investigate the epigenetic alterations on hAT-MSCs during environmental mechanical forces and to consider how the knowledge gained through these studies may foster new means of symptoms prevention and management of ectopic bone formation in the clinic., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We report on the first experimental observations of quasichanneling oscillations, recently seen in simulations and described theoretically. Although above-barrier particles penetrating a single crystal are generally seen as behaving almost as in an amorphous substance, distinct oscillation peaks nevertheless appear for particles in that category. The quasichanneling oscillations were observed at SLAC National Accelerator Laboratory by aiming 20.35 GeV positrons and electrons at a thin silicon crystal bent to a radius of R=0.15  m, exploiting the quasimosaic effect. For electrons, two relatively faint quasichanneling peaks were observed, while for positrons, seven quasichanneling peaks were clearly identified.

Inherited optic neuropathies are a genetically diverse group of disorders mainly characterized by visual loss and optic atrophy. Since the first recognition of Leber's hereditary optic neuropathy, several genetic defects altering primary mitochondrial respiration have been proposed to contribute to the development of syndromic and non-syndromic optic neuropathies. Moreover, the genomics and imaging revolution in the past decade has increased diagnostic efficiency and accuracy, allowing recognition of a link between mitochondrial dynamics machinery and a broad range of inherited neurodegenerative diseases involving the optic nerve. Mutations of novel genes modifying mainly the balance between mitochondrial fusion and fission have been shown to lead to overlapping clinical phenotypes ranging from isolated optic atrophy to severe, sometimes lethal multisystem disorders, and are reviewed herein. Given the particular vulnerability of retinal ganglion cells to mitochondrial dysfunction, the accessibility of the eye as a part of the central nervous system and improvements in technical imaging concerning assessment of the retinal nerve fiber layer, optic nerve evaluation becomes critical - even in asymptomatic patients - for correct diagnosis, understanding and early treatment of these complex and enigmatic clinical entities., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We propose a unique program of measurements of electric and magnetic dipole moments of charm, beauty and strange charged baryons at the LHC, based on the phenomenon of spin precession of channeled particles in bent crystals. Studies of crystal channeling and spin precession of positively- and negatively-charged particles are presented, along with feasibility studies and expected sensitivities for the proposed experiment using a layout based on the LHCb detector., (© The Author(s) 2017.)