Vascular complications of cancer chemotherapy

Development of new anticancer drugs has resulted in improved mortality rates and 5-year survival rates in patients with cancer. However, many of the modern chemotherapies are associated with cardiovascular toxicities that increase cardiovascular risk in cancer patients, including hypertension, thrombosis, heart failure, cardiomyopathy, and arrhythmias. These limitations restrict treatment options and might negatively affect the management of cancer. The cardiotoxic effects of older chemotherapeutic drugs such as alkylating agents, antimetabolites, and anticancer antibiotics have been known for a while. The newer agents, such as the antiangiogenic drugs that inhibit vascular endothelial growth factor signalling are also associated with cardiovascular pathology, especially hypertension, thromboembolism, myocardial infarction, and proteinuria. Exact mechanisms by which vascular endothelial growth factor inhibitors cause these complications are unclear but impaired endothelial function, vascular and renal damage, oxidative stress, and thrombosis might be important. With increasing use of modern chemotherapies and prolonged survival of cancer patients, the incidence of cardiovascular disease in this patient population will continue to increase. Accordingly, careful assessment and management of cardiovascular risk factors in cancer patients by oncologists and cardiologists working together is essential for optimal care so that prolonged cancer survival is not at the expense of increased cardiovascular events

Drug treatment of hypertension: focus on vascular health

Hypertension, the most common preventable risk factor for cardiovascular disease and death, is a growing health burden. Serious cardiovascular complications result from target organ damage including cerebrovascular disease, heart failure, ischaemic heart disease and renal failure. While many systems contribute to blood pressure (BP) elevation, the vascular system is particularly important because vascular dysfunction is a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, arterial remodelling, vascular inflammation and increased stiffness. Antihypertensive drugs that influence vascular changes associated with high BP have greater efficacy for reducing cardiovascular risk than drugs that reduce BP, but have little or no effect on the adverse vascular phenotype. Angiotensin converting enzyme ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) improve endothelial function and prevent vascular remodelling. Calcium channel blockers also improve endothelial function, although to a lesser extent than ACEIs and ARBs. Mineralocorticoid receptor blockers improve endothelial function and reduce arterial stiffness, and have recently become more established as antihypertensive drugs. Lifestyle factors are essential in preventing the adverse vascular changes associated with high BP and reducing associated cardiovascular risk. Clinicians and scientists should incorporate these factors into treatment decisions for patients with high BP, as well as in the development of new antihypertensive drugs that promote vascular health

Semiparametric Bayesian models for human brain mapping

Functional magnetic resonance imaging (fMRI) has led to enormous progress in human brain mapping. Adequate analysis of the massive spatiotemporal data sets generated by this imaging technique, combining parametric and non-parametric components, imposes challenging problems in statistical modelling. Complex hierarchical Bayesian models in combination with computer-intensive Markov chain Monte Carlo inference are promising tools.The purpose of this paper is twofold. First, it provides a review of general semiparametric Bayesian models for the analysis of fMRI data. Most approaches focus on important but separate temporal or spatial aspects of the overall problem, or they proceed by stepwise procedures. Therefore, as a second aim, we suggest a complete spatiotemporal model for analysing fMRI data within a unified semiparametric Bayesian framework. An application to data from a visual stimulation experiment illustrates our approach and demonstrates its computational feasibility

Single-particle and Interaction Effects on the Cohesion and Transport and Magnetic Properties of Metal Nanowires at Finite Voltages

The single-particle and interaction effects on the cohesion, electronic transport, and some magnetic properties of metallic nanocylinders have been studied at finite voltages by using a generalized mean-field electron model. The electron-electron interactions are treated in the self-consistent Hartree approximation. Our results show the single-particle effect is dominant in the cohesive force, while the nonzero magnetoconductance and magnetotension coefficients are attributed to the interaction effect. Both single-particle and interaction effects are important to the differential conductance and magnetic susceptibility.Comment: 5 pages, 6 figure

Waiting time distribution for electron transport in a molecular junction with electron-vibration interaction

On the elementary level, electronic current consists of individual electron tunnelling events that are separated by random time intervals. The waiting time distribution is a probability to observe the electron transfer in the detector electrode at time $t+\tau$ given that an electron was detected in the same electrode at earlier time $t$. We study waiting time distribution for quantum transport in a vibrating molecular junction. By treating the electron-vibration interaction exactly and molecule-electrode coupling perturbatively, we obtain master equation and compute the distribution of waiting times for electron transport. The details of waiting time distributions are used to elucidate microscopic mechanism of electron transport and the role of electron-vibration interactions. We find that as nonequilibrium develops in molecular junction, the skewness and dispersion of the waiting time distribution experience stepwise drops with the increase of the electric current. These steps are associated with the excitations of vibrational states by tunnelling electrons. In the strong electron-vibration coupling regime, the dispersion decrease dominates over all other changes in the waiting time distribution as the molecular junction departs far away from the equilibrium

The magnetic environment in the central region of nearby galaxies

The central regions of galaxies harbor some of the most extreme physical phenomena, including dense stellar clusters, non-circular motions of molecular clouds and strong and pervasive magnetic field structures. In particular, radio observations have shown that the central few hundred parsecs of our Galaxy has a striking magnetic field configuration. It is not yet clear whether these magnetic structures are unique to our Milky Way or a common feature of all similar galaxies. Therefore, we report on (a) a new radio polarimetric survey of the central 200 pc of the Galaxy to better characterize the magnetic field structure and (b) a search for large-scale and organized magnetized structure in the nuclear regions of nearby galaxies using data from the Very Large Array (VLA) archive. The high angular resolution of the VLA allows us to study the central 1 kpc of the nearest galaxies to search for magnetized nuclear features similar to what is detected in our own Galactic center. Such magnetic features play a important role in the nuclear regions of galaxies in terms of gas transport and the physical conditions of the interstellar medium in this unusual region of galaxies.Comment: 8 pages; Proceedings for "The Universe under the Microscope" (AHAR 2008), held in Bad Honnef (Germany) in April 2008, to be published in Journal of Physics: Conference Series by Institute of Physics Publishing, R. Schoedel, A. Eckart, S. Pfalzner, and E. Ros (eds.

VLA Detection of the Ionized Stellar Winds Arising from Massive Stars in the Galactic Center Arches Cluster

The Galactic center Arches stellar cluster, detected and studied until now only in the near-infrared, is comprised of at least one hundred massive (M>20 Msun) stars. Here we report the detection at centimeter wavelengths of radio continuum emission from eight radio sources associated with the cluster. Seven of these radio sources have rising spectral indices between 4.9 and 8.5 GHz and coincide spatially with the brightest stars in the cluster, as determine from JHK photometry and Brackett alpha and Brackett Gamma spectroscopy. Our results confirm the presence of powerful ionized winds in these stars. The eighth radio source has a nonthermal spectrum and its nature is yet unclear, but it could be associated with a lower mass young star in the cluster.Comment: 6 pages, 2 embedded figures, accepted to ApJLetter

Toxicity of cancer therapy: what the cardiologist needs to know about angiogenesis inhibitors

Clinical outcomes for patients with a wide range of malignancies have improved substantially over the last two decades. Tyrosine kinase inhibitors (TKIs) are potent signalling cascade inhibitors and have been responsible for significant advances in cancer therapy. By inhibiting vascular endothelial growth factor receptor (VEGFR)-mediated tumour blood vessel growth, VEGFR-TKIs have become a mainstay of treatment for a number of solid malignancies. However, the incidence of VEGFR-TKI-associated cardiovascular toxicity is substantial and previously under-recognised. Almost all patients have an acute rise in blood pressure, and the majority develop hypertension. They are associated with the development of left ventricular systolic dysfunction (LVSD), heart failure and myocardial ischaemia and can have effects on myocardial repolarisation. Attention should be given to rigorous baseline assessment of patients prior to commencing VEGFR-TKIs, with careful consideration of baseline cardiovascular risk factors. Baseline blood pressure measurement, ECG and cardiac imaging should be performed routinely. Hypertension management currently follows national guidelines, but there may be a future role forendothelin-1 antagonism in the prevention or treatment of VEGFR-TKI-associated hypertension. VEGFR-TKI-associated LVSD appears to be independent of dose and is reversible. Patients who develop LVSD and heart failure should be managed with conventional heart failure therapies, but the role of prophylactic therapy is yet to be defined. Serial monitoring of left ventricular function and QT interval require better standardisation and coordinated care. Management of these complex patients requires collaborative, cardio-oncology care to allow the true therapeutic potential from cancer treatment while minimising competing cardiovascular effects