Magnetic Navigation in Percutaneous Cardiac Intervention

Magnetic navigation is the use of a magnetic fi eld to re-orientate a magnetically-enabled wire or device. The fi eld is directed by external magnets that are moved by a computercontrolled system. This technology could improve percutaneous coronary interventional procedures as it improves 3 specifi c and complementary capabilities, namely precise tip adjustability, computer-enhanced, image-guided tip orientation, and computer–enhanced image processing. Although this technology is relatively new, it already appears that this system can equal, and even improve on, current conventional wire technique. The current usability, combined with the exciting potential of future developments, could result in a formidable adjunct to PCI. This thesis deals with the early use of the system, development of diff erent strategies for the exploitation of the unique novel features that the system has. Specifi cally it will describe a number of areas. 1. Background, history and system description: The aim of this introduction is to provide a brief description of the background of magnetic procedures with respect to Stereotaxis Inc, and a description of the magnetic moment, and a short description of the current system together with the specially-produced wires. 2. Feasibility in phantom models, and initial system development: This section deals with aspects related to feasibility of use, validation of the software, and initial experience in diff erent clinical situations and fi nally with the potential use in treating one of the sequelae of coronary disease i.e. poor left ventricular function by the possible delivery of cardiac stem cells. 3. Initial experience in clinical practice and illustrative case reports: This section deals with the clinical use in percutaneous coronary intervention concentrating on the initial patient studies. 4. Investigation of benefi ts in subgroups: This section concentrates on particular subsets of coronary intervention patients and the specifi c hypotheses that can be drawn from these

Pre-exposure prophylaxis for HIV prevention: how to predict success

Use of antiretroviral drugs to prevent sexual transmission of HIV-1 has been a critical priority since their development. In the past 2 years results from seven important prevention trials have been reported (table). One of the trials, HPTN 052, showed nearly complete prevention of HIV transmission when viraemia was suppressed. The other studies focused on antiretroviral agents for pre-exposure prophylaxis: two used 1% tenofovir gel (CAPRISA 004 and VOICE), four used oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in combination (iPrEX, TDF2, Partners in Prevention [PIP], and Fem-PrEP), and two used oral TDF alone (VOICE and PIP). Somewhat confusingly, the findings of these studies have led to reports both of successful prevention of HIV infection (CAPRISA 004, iPrEx, TDF2, and PIP) and of futility (VOICE and Fem-PrEP)

The Asymptotic distribution of circles in the orbits of Kleinian groups

Let P be a locally finite circle packing in the plane invariant under a non-elementary Kleinian group Gamma and with finitely many Gamma-orbits. When Gamma is geometrically finite, we construct an explicit Borel measure on the plane which describes the asymptotic distribution of small circles in P, assuming that either the critical exponent of Gamma is strictly bigger than 1 or P does not contain an infinite bouquet of tangent circles glued at a parabolic fixed point of Gamma. Our construction also works for P invariant under a geometrically infinite group Gamma, provided Gamma admits a finite Bowen-Margulis-Sullivan measure and the Gamma-skinning size of P is finite. Some concrete circle packings to which our result applies include Apollonian circle packings, Sierpinski curves, Schottky dances, etc.Comment: 31 pages, 8 figures. Final version. To appear in Inventiones Mat

Adverse effects of fenofibrate in mice deficient in the protein quality control regulator, CHIP

We previously reported how the loss of CHIP expression (Carboxyl terminus of Hsc70-Interacting Protein) during pressure overload resulted in robust cardiac dysfunction, which was accompanied by a failure to maintain ATP levels in the face of increased energy demand. In this study, we analyzed the cardiac metabolome after seven days of pressure overload and found an increase in long-chain and medium-chain fatty acid metabolites in wild-type hearts. This response was attenuated in mice that lack expression of CHIP (CHIP-/-). These findings suggest that CHIP may play an essential role in regulating oxidative metabolism pathways that are regulated, in part, by the nuclear receptor PPARα (Peroxisome Proliferator-Activated Receptor alpha). Next, we challenged CHIP-/- mice with the PPARα agonist called fenofibrate. We found that treating CHIP-/- mice with fenofibrate for five weeks under non-pressure overload conditions resulted in decreased skeletal muscle mass, compared to wild-type mice, and a marked increase in cardiac fibrosis accompanied by a decrease in cardiac function. Fenofibrate resulted in decreased mitochondrial cristae density in CHIP-/- hearts as well as decreased expression of genes involved in the initiation of autophagy and mitophagy, which suggests that a metabolic challenge, in the absence of CHIP expression, impacts pathways that contribute to mitochondrial quality control. In conclusion, in the absence of functional CHIP expression, fenofibrate results in unexpected skeletal muscle and cardiac pathologies. These findings are particularly relevant to patients harboring loss-of-function mutations in CHIP and are consistent with a prominent role for CHIP in regulating cardiac metabolism

Clinical Evidence Supports a Protective Role for CXCL5 in Coronary Artery Disease

Our goal was to measure the association of CXCL5 and molecular phenotypes associated with coronary atherosclerosis severity in patients at least 65 years old. CXCL5 is classically defined as a proinflammatory chemokine, but its role in chronic inflammatory diseases, such as coronary atherosclerosis, is not well defined. We enrolled individuals who were at least 65 years old and undergoing diagnostic cardiac catheterization. Coronary artery disease (CAD) severity was quantified in each subject via coronary angiography by calculating a CAD score. Circulating CXCL5 levels were measured from plasma, and both DNA genotyping and mRNA expression levels in peripheral blood mononuclear cells were quantified via microarray gene chips. We observed a negative association of CXCL5 levels with CAD at an odds ratio (OR) of 0.46 (95% CI, 0.27–0.75). Controlling for covariates, including sex, statin use, hypertension, hyperlipidemia, obesity, self-reported race, smoking, and diabetes, the OR was not significantly affected [OR, 0.54 (95% CI, 0.31–0.96)], consistent with a protective role for CXCL5 in coronary atherosclerosis. We also identified 18 genomic regions with expression quantitative trait loci of genes correlated with both CAD severity and circulating CXCL5 levels. Our clinical findings are consistent with the emerging link between chemokines and atherosclerosis and suggest new therapeutic targets for CAD

Impact of percutaneous coronary intervention timing on 5-year outcome in patients with non-ST-segment elevation acute coronary syndromes. The ‘wait a day’ approach might be safer

Background The OPTIMA trial was a randomised multicentre trial exploring the influence of the timing of percutaneous coronary intervention (PCI) on patient outcomes in an intermediate to high risk non-ST-elevation acute coronary syndrome (NSTE-ACS) population. In order to decide the best treatment strategy for patients presenting with NSTEACS, long-term outcomes are essential. Methods Five-year follow-up data from 133 of the 142 patients could be retrieved (94 %). The primary endpoint was a composite of death and spontaneous myocardial infarction (MI). Spontaneous MI was defined as MI occurring more than 30 days after randomisation. Secondary endpoints were the individual outcomes of death, spontaneous MI or re-PCI. Results No significant difference with respect to the primary endpoint was observed (17.8 vs. 10.1 %; HR 1.55, 95 % CI: 0.73–4.22, p = 0.21). There was no significant difference in mortality rate. However, spontaneous MI was significantly more common in the group receiving immediate PCI (11.0 vs. 1.4 %; HR 4.46, 95 % CI: 1.21–16.50, p = 0.02). We did not find a significant difference between the groups with respect to re-PCI rate. Conclusion There was no difference in the composite of death and spontaneous MI. The trial suggests an increased long-term risk of spontaneous MI for patients treated with immediate PCI

The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

Production and Decay of D_1(2420)^0 and D_2^*(2460)^0

We have investigated $D^{+}\pi^{-}$ and $D^{*+}\pi^{-}$ final states and observed the two established $L=1$ charmed mesons, the $D_1(2420)^0$ with mass $2421^{+1+2}_{-2-2}$ MeV/c$^{2}$ and width $20^{+6+3}_{-5-3}$ MeV/c$^{2}$ and the $D_2^*(2460)^0$ with mass $2465 \pm 3 \pm 3$ MeV/c$^{2}$ and width $28^{+8+6}_{-7-6}$ MeV/c$^{2}$. Properties of these final states, including their decay angular distributions and spin-parity assignments, have been studied. We identify these two mesons as the $j_{light}=3/2$ doublet predicted by HQET. We also obtain constraints on {\footnotesize $\Gamma_S/(\Gamma_S + \Gamma_D)$} as a function of the cosine of the relative phase of the two amplitudes in the $D_1(2420)^0$ decay.Comment: 15 pages in REVTEX format. hardcopies with figures can be obtained by sending mail to: [email protected]