The major geoeffective solar eruptions of 2012 March 7: comprehensive Sun-to-Earth analysis

During the interval 2012 March 7-11 the geospace experienced a barrage of intense space weather phenomena including the second largest geomagnetic storm of solar cycle 24 so far. Significant ultra-low-frequency wave enhancements and relativistic-electron dropouts in the radiation belts, as well as strong energetic-electron injection events in the magnetosphere were observed. These phenomena were ultimately associated with two ultra-fast (>2000 kms-1) coronal mass ejections (CMEs), linked to two X-class flares launched on early 2012 March 7. Given that both powerful events originated from solar active region NOAA 11429 and their onsets were separated by less than an hour, the analysis of the two events and the determination of solar causes and geospace effects are rather challenging. Using satellite data from a flotilla of solar, heliospheric and magnetospheric missions a synergistic Sun-to-Earth study of diverse observational solar, interplanetary and magnetospheric data sets was performed. It was found that only the second CME was Earth-directed. Using a novel method, we estimated its near-Sun magnetic field at 13R⊙ to be in the range [0.01, 0.16] G. Steep radial fall-offs of the near-Sun CME magnetic field are required to match the magnetic fields of the corresponding interplanetary CME (ICME) at 1 AU. Perturbed upstream solar-wind conditions, as resulting from the shock associated with the Earth-directed CME, offer a decent description of its kinematics. The magnetospheric compression caused by the arrival at 1 AU of the shock associated with the ICME was a key factor for radiation-belt dynamics.Publisher PDFPeer reviewe

Regulation of Cytokine-Mediated Vascular Permeability Under Flow-Induced Shear Stress

Ph.D. University of Hawaii at Manoa 2015.Includes bibliographical references.Endothelial cells form the innermost lining of blood vessels throughout the circulatory system. They exhibit a remarkable ability to adapt rapidly to biomechanical and biochemical stimuli from their microenvironment. Vascular endothelial cells play an essential role during the onset of inflammatory conditions and sepsis. Sepsis accounts for the highest number of mortalities in non-cardiac intensive care units and is linked to numerous other underlying conditions including cancer, inflammatory conditions and diabetes. Cancer patients, in particular, are especially susceptible to infections that lead to sepsis and show significantly higher mortality rates due to the immunocompromised nature of the host defense system. Currently, there are no available treatments for sepsis. Furthermore, TNFα has been implicated as one of the major proinflammatory cytokines in sepsis. In the current work, we used physiologically relevant shear stress rates and translated them into a well-controlled in vitro system applying fluid shear stress onto primary endothelial microvascular endothelial cells. We identified a complex formed by the active form of the small GTPase R-Ras and the cytoskeletal scaffold protein filamin A (FLNa) that can regulate TNFα-mediated activation of endothelial cells under fluid shear stress conditions. R-Ras binds directly to repeat 3 of FLNa forming a complex that is necessary for endothelial barrier integrity. We show here that activated GTP-bound R-Ras blocks vascular permeability. Permeability is monitored using the electrical cell impedance spectroscopy (ECIS) method that acquires real-time transendothelial electrical resistance (TEER) values. From the electrical resistance, impedance and capacitance, endothelial permeability can be derived by employing the ECIS model and quantified at nanoscale precision levels concurrently with endothelial cells subjected to fluid shear stress. We also demonstrate a novel platform comprised of ECIS and physiologically relevant fluid shear stress levels to test novel inhibitors or compounds that block TNFα-mediated vascular permeability. Thus, we show that the R-Ras/FLNa complex is important in regulating vascular endothelial permeability under fluid shear stress conditions. This work may offer insights into the regulation of endothelial permeability by providing novel targets to block vascular hyperpermeability or leakiness

Therapeutic Approach and Procedures in Treatment of Fracture Patella

FyzioterapieFaculty of Physical Education and SportFakulta tělesné výchovy a sport

The relationship between stress, social capital and quality of education among medical residents

Objective: The educational climate is a key factor in medical education. The study aims to examine the relationship between trainee doctors' perceptions of hospital educational environment, stress and social capital. A cross-sectional study among 104 trainee doctors working in a Greek public hospital was conducted. According to the main hypotheses, perceptions of clinical training are positively associated with social capital and negatively with stress. Results: Perceptions of autonomy dimension of training quality was positively related to community participation, tolerance of diversity and total social capital. Perceptions of teaching and social support dimensions of the quality of education were positively correlated with community participation. All training quality subscales were negatively correlated with almost all working stress subscales. Analysis revealed significantly higher scores in autonomy perceptions for those who evaluated their undergraduate studies positively. Females had a significantly lower score in perceptions of teaching and social support scales

Design, characterization and evaluation of a laser-guided focused ultrasound system for preclinical investigations

Abstract Background The clinical applications of transcranial focused ultrasound continue to expand and include ablation as well as drug delivery applications in the brain, where treatments are typically guided by MRI. Although MRI-guided focused ultrasound systems are also preferred for many preclinical investigations, they are expensive to purchase and operate, and require the presence of a nearby imaging center. For many basic mechanistic studies, however, MRI is not required. The purpose of this study was to design, construct, characterize and evaluate a portable, custom, laser-guided focused ultrasound system for noninvasive, transcranial treatments in small rodents. Methods The system comprised an off-the-shelf focused ultrasound transducer and amplifier, with a custom cone fabricated for direct coupling of the transducer to the head region. A laser-guidance apparatus was constructed with a 3D stage for accurate positioning to 1 mm. Pressure field simulations were performed to demonstrate the effects of the coupling cone and the sealing membrane, as well as for determining the location of the focus and acoustic transmission across rat skulls over a range of sizes. Hydrophone measurements and exposures in hydrogels were used to assess the accuracy of the simulations. In vivo treatments were performed in rodents for opening the blood–brain barrier and to assess the performance and accuracy of the system. The effects of varying the acoustic pressure, microbubble dose and animal size were evaluated in terms of efficacy and safety of the treatments. Results The simulation results were validated by the hydrophone measurements and exposures in the hydrogels. The in vivo treatments demonstrated the ability of the system to open the blood–brain barrier. A higher acoustic pressure was required in larger-sized animals, as predicted by the simulations and transmission measurements. In a particular sized animal, the degree of blood–brain barrier opening, and the safety of the treatments were directly associated with the microbubble dose. Conclusion The focused ultrasound system that was developed was found to be a cost-effective alternative to MRI-guided systems as an investigational device that is capable of accurately providing noninvasive, transcranial treatments in rodents

Nanoparticle-assisted, image-guided laser interstitialthermal therapy for cancer treatment

Laser interstitial thermal therapy (LITT) guided by magnetic resonance imaging (MRI) is a new treatment option for patients with brain and non-central nervous system (non-CNS) tumors. MRI guidance allows for precise placement of optical fiber in the tumor, while MR thermometry provides real-time monitoring and assessment of thermal doses during the procedure. Despite promising clinical results, LITT complications relating to brain tumor procedures, such as hemorrhage, edema, seizures, and thermal injury to nearby healthy tissues, remain a significant concern. To address these complications, nanoparticles offer unique prospects for precise interstitial hyperthermia applications that increase heat transport within the tumor while reducing thermal impacts on neighboring healthy tissues. Furthermore, nanoparticles permit the co-delivery of therapeutic compounds that not only synergize with LITT, but can also improve overall effectiveness and safety. In addition, efficient heat-generating nanoparticles with unique optical properties can enhance LITT treatments through improved real-time imaging and thermal sensing. This review will focus on (1) types of inorganic and organic nanoparticles for LITT; (2) in vitro, in silico, and ex vivo studies that investigate nanoparticles' effect on light–tissue interactions; and (3) the role of nanoparticle formulations in advancing clinically relevant image-guided technologies for LITT.https://doi.org/10.1002/wnan.182