Adjuvant therapeutic potential of tonabersat in the standard treatment of glioblastoma : a preclinical F98 glioblastoma rat model study

Purpose Even with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12-15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma. Cx43-mediated gap junctional communication has been observed between tumor cells, between astrocytes and between tumor cells and astrocytes. Therefore, gap junction directed therapy using a pharmacological suppressor or modulator, such as tonabersat, could be a promising target in the treatment of GB. In this preclinical study, we evaluated the possible therapeutic potential of tonabersat in the F98 model. Procedures Female Fischer rats were inoculated with +/- 25.000 F98 tumor cells in the right frontal lobe. Eight days post-inoculation contrast-enhanced T1-weighted (CE-T1w) magnetic resonance (MR) images were acquired to confirm tumor growth in the brain. After tumor confirmation, rats were randomized into a Control Group, a Connexin Modulation Group (CM), a Standard Medical Treatment Group (ST), and a Standard Medical Treatment with adjuvant Connexin Modulation Group (STCM). To evaluate therapy response, T2-weighted (T2w) and CE-T1w sequences were acquired at several time points. Tumor volume analysis was performed on CE-T1w images and statistical analysis was performed using a linear mixed model. Results Significant differences in estimated geometric mean tumor volumes were found between the ST Group and the Control Group and also between the STCM Group and the Control Group. In addition, significant differences in estimated geometric mean tumor volumes between the ST Group and the STCM Group were demonstrated. No significant differences in estimated geometric mean tumor volumes were found between the Control Group and the CM Group. Conclusion Our results demonstrate a therapeutic potential of tonabersat for the treatment of GB when used in combination with radiotherapy and temozolomide chemotherapy

Confinement effects in a guided-wave interferometer with millimeter-scale arm separation

Guided-wave atom interferometers measure interference effects using atoms held in a confining potential. In one common implementation, the confinement is primarily two-dimensional, and the atoms move along the nearly free dimension under the influence of an off-resonant standing wave laser beam. In this configuration, residual confinement along the nominally free axis can introduce a phase gradient to the atoms that limits the arm separation of the interferometer. We experimentally investigate this effect in detail, and show that it can be alleviated by having the atoms undergo a more symmetric motion in the guide. This can be achieved by either using additional laser pulses or by allowing the atoms to freely oscillate in the potential. Using these techniques, we demonstrate interferometer measurement times up to 72 ms and arm separations up to 0.42 mm with a well controlled phase, or times of 0.91 s and separations of 1.7 mm with an uncontrolled phase.Comment: 14 pages, 6 figure

Control of energy density inside disordered medium by coupling to open or closed channels

We demonstrate experimentally an efficient control of light intensity distribution inside a random scattering system. The adaptive wavefront shaping technique is applied to a silicon waveguide containing scattering nanostructures, and the on-chip coupling scheme enables access to all input spatial modes. By selectively coupling the incident light to open or closed channels of the disordered system, we not only vary the total energy stored inside the system by 7.4 times, but also change the energy density distribution from an exponential decay to a linear decay and to a profile peaked near the center. This work provides an on-chip platform for controlling light-matter interactions in turbid media

Effect of a reduction in glomerular filtration rate after nephrectomy on arterial stiffness and central hemodynamics: rationale and design of the EARNEST study

Background: There is strong evidence of an association between chronic kidney disease (CKD) and cardiovascular disease. To date, however, proof that a reduction in glomerular filtration rate (GFR) is a causative factor in cardiovascular disease is lacking. Kidney donors comprise a highly screened population without risk factors such as diabetes and inflammation, which invariably confound the association between CKD and cardiovascular disease. There is strong evidence that increased arterial stiffness and left ventricular hypertrophy and fibrosis, rather than atherosclerotic disease, mediate the adverse cardiovascular effects of CKD. The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR in a prospective fashion. At the same time, the proposed study will address ongoing safety concerns that persist because most longitudinal outcome studies have been undertaken at single centers and compared donor cohorts with an inappropriately selected control group.<p></p> Hypotheses: The reduction in GFR accompanying uninephrectomy causes (1) a pressure-independent increase in aortic stiffness (aortic pulse wave velocity) and (2) an increase in peripheral and central blood pressure.<p></p> Methods: This is a prospective, multicenter, longitudinal, parallel group study of 440 living kidney donors and 440 healthy controls. All controls will be eligible for living kidney donation using current UK transplant criteria. Investigations will be performed at baseline and repeated at 12 months in the first instance. These include measurement of arterial stiffness using applanation tonometry to determine pulse wave velocity and pulse wave analysis, office blood pressure, 24-hour ambulatory blood pressure monitoring, and a series of biomarkers for cardiovascular and bone mineral disease.<p></p> Conclusions: These data will prove valuable by characterizing the direction of causality between cardiovascular and renal disease. This should help inform whether targeting reduced GFR alongside more traditional cardiovascular risk factors is warranted. In addition, this study will contribute important safety data on living kidney donors by providing a longitudinal assessment of well-validated surrogate markers of cardiovascular disease, namely, blood pressure and arterial stiffness. If any adverse effects are detected, these may be potentially reversed with the early introduction of targeted therapy. This should ensure that kidney donors do not come to long-term harm and thereby preserve the ongoing expansion of the living donor transplant program.<p></p&gt

Camera System Performance Derived from Natural Scenes

The Modulation Transfer Function (MTF) is a well-established measure of camera system performance, commonly employed to characterize optical and image capture systems. It is a measure based on Linear System Theory; thus, its use relies on the assumption that the system is linear and stationary. This is not the case with modern-day camera systems that incorporate non-linear image signal processes (ISP) to improve the output image. Non-linearities result in variations in camera system performance, which are dependent upon the specific input signals. This paper discusses the development of a novel framework, designed to acquire MTFs directly from images of natural complex scenes, thus making the use of traditional test charts with set patterns redundant. The framework is based on extraction, characterization and classification of edges found within images of natural scenes. Scene derived performance measures aim to characterize non-linear image processes incorporated in modern cameras more faithfully. Further, they can produce ‘live’ performance measures, acquired directly from camera feeds

Effects of epitaxial strain on the growth mechanism of YBa2Cu3O7-x thin films in [YBa2Cu3O7-x / PrBa2Cu3O7-x] superlattices

We report on the growth mechanism of YBa2Cu3O7-x (YBCO). Our study is based on the analysis of ultrathin, YBa2Cu3O7-x layers in c-axis oriented YBa2Cu3O7-x / PrBa2Cu3O7-x superlattices. We have found that the release of epitaxial strain in very thin YBCO layers triggers a change in the dimensionality of the growth mode. Ultrathin, epitaxially strained, YBCO layers with thickness below 3 unit cells grow in a block by block two dimensional mode coherent over large lateral distances. Meanwhile, when thickness increases, and the strain relaxes, layer growth turns into three dimensional, resulting in rougher layers and interfaces.Comment: 10 pages + 9 figures, accepted in Phys. Rev.