Emerging Therapies for Advanced Clear Cell Renal Cell Carcinoma

Multiple combinational regimens have recently been approved and are now considered the standard of care for patients with advanced clear cell renal cell carcinoma (RCC). Several additional combinational regimens are deep in clinical assessment and are likely to soon join the crowded front-line therapeutic landscape. Most of these regimens are combinations of agents already approved as single-agents in RCC including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors. While these new front-line regimens are associated with reliably high response rates and prolonged survival, complete and durable remissions remain limited to a small subset of patients and the vast majority of patients continue to require subsequent therapy. The need for the continued development of novel agents in RCC persists and efforts have focused on agents targeting the molecular biology of clear cell RCC and novel immunotherapies including cytokines. In this review, we discuss the progress in the development of these novel therapies in the context of the evolving standard of care for patients with advanced clear cell RCC

Analyzing The Determinants Of Attitude, Behavior, And Satisfaction On Imported Products: Implications For The Growing Food And Beverage Industry

The aims of this study are to determine the influences of attitude formation, behavior, and satisfaction, with specific reference to the products of the food and beverage industry of Southeast Asia. This study employs the theoretical frameworks of the Theory of Planned Behavior and others to understand the psychological processes that take place between forming beliefs and actual consumption. The key findings reveal that consumers are influenced by both the traditional food attributes such as quality, price, and availability, while also extraneously influenced both by perceived family influence and perceived societal influence in their attitude formation. These factors, through the proposed model of study, were also statistically proven to influence behavioral intention of the sample group through willingness to purchase. In addition, satisfaction with prior purchase was also shown to be a determinant of consumer attitude, while the determinants of expected satisfaction were inconclusive. The results of the modelling and analyses of this study indicate the necessity for the concurrent development of innovative marketing strategies and quality improvements in the industry as it follows its projected growth course and outward expansion

Magnetic fields in galaxies: I. Radio disks in local late-type galaxies

We develop an analytical model to follow the cosmological evolution of magnetic fields in disk galaxies. Our assumption is that fields are amplified from a small seed field via magnetohydrodynamical (MHD) turbulence. We further assume that this process is fast compared to other relevant timescales, and occurs principally in the cold disk gas. We follow the turbulent energy density using the Shabala & Alexander (2009) galaxy formation and evolution model. Three processes are important to the turbulent energy budget: infall of cool gas onto the disk and supernova feedback increase the turbulence; while star formation removes gas and hence turbulent energy from the cold gas. Finally, we assume that field energy is continuously transferred from the incoherent random field into an ordered field by differential galactic rotation. Model predictions are compared with observations of local late type galaxies by Fitt & Alexander (1993) and Shabala et al. (2008). The model reproduces observed magnetic field strengths and luminosities in low and intermediate-mass galaxies. These quantities are overpredicted in the most massive hosts, suggesting that inclusion of gas ejection by powerful AGNs is necessary in order to quench gas cooling and reconcile the predicted and observed magnetic field strengths.Comment: 10 pages, 8 figures; MNRAS in pres

HDAC2 expression in parvalbumin interneurons regulates synaptic plasticity in the mouse visual cortex

An experience-dependent postnatal increase in GABAergic inhibition in the visual cortex is important for the closure of a critical period of enhanced synaptic plasticity. Although maturation of the subclass of parvalbumin (Pv)-expressing GABAergic interneurons is known to contribute to critical period closure, the role of epigenetics on cortical inhibition and synaptic plasticity has not been explored. The transcription regulator, histone deacetylase 2 (HDAC2), has been shown to modulate synaptic plasticity and learning processes in hippocampal excitatory neurons. We found that genetic deletion of HDAC2 specifically from Pv interneurons reduces inhibitory input in the visual cortex of adult mice and coincides with enhanced long-term depression that is more typical of young mice. These findings show that HDAC2 loss in Pv interneurons leads to a delayed closure of the critical period in the visual cortex and supports the hypothesis that HDAC2 is a key negative regulator of synaptic plasticity in the adult brain.National Institute of Neurological Diseases and Stroke (U.S.) (Grant NS078839)National Institute on Aging (Grant NS078839