Atenolol versus losartan in children and young adults with Marfan's syndrome

BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period

The Ovarian Cancer Chemokine Landscape Is Conducive to Homing of Vaccine-Primed and CD3/CD28-Costimulated T Cells Prepared for Adoptive Therapy.

PURPOSE: Chemokines are implicated in T-cell trafficking. We mapped the chemokine landscape in advanced stage ovarian cancer and characterized the expression of cognate receptors in autologous dendritic cell (DC)-vaccine primed T cells in the context of cell-based immunotherapy. EXPERIMENTAL DESIGN: The expression of all known human chemokines in patients with primary ovarian cancer was analyzed on two independent microarray datasets and validated on tissue microarray. Peripheral blood T cells from five HLA-A2 patients with recurrent ovarian cancer, who previously received autologous tumor DC vaccine, underwent CD3/CD28 costimulation and expansion ex vivo. Tumor-specific T cells were identified by HER2/neu pentamer staining and were evaluated for the expression and functionality of chemokine receptors important for homing to ovarian cancer. RESULTS: The chemokine landscape of ovarian cancer is heterogeneous with high expression of known lymphocyte-recruiting chemokines (CCL2, CCL4, and CCL5) in tumors with intraepithelial T cells, whereas CXCL10, CXCL12, and CXCL16 are expressed quasi-universally, including in tumors lacking tumor-infiltrating T cells. DC-vaccine primed T cells were found to express the cognate receptors for the above chemokines. Ex vivo CD3/CD28 costimulation and expansion of vaccine-primed Tcells upregulated CXCR3 and CXCR4, and enhanced their migration toward universally expressed chemokines in ovarian cancer. CONCLUSIONS: DC-primed tumor-specific T cells are armed with the appropriate receptors to migrate toward universal ovarian cancer chemokines, and these receptors are further upregulated by ex vivo CD3/CD28 costimulation, which render T cells more fit for migrating toward these chemokines. Clin Cancer Res; 21(12); 2840-50. ©2015 AACR

Hidden degree of freedom and critical states in a two-dimensional electron gas in the presence of a random magnetic field

We establish the existence of a hidden degree of freedom and the critical states of a spinless electron system in a spatially-correlated random magnetic field with vanishing mean. Whereas the critical states are carried by the zero-field contours of the field landscape, the hidden degree of freedom is recognized as being associated with the formation of vortices in these special contours. It is argued that, as opposed to the coherent backscattering mechanism of weak localization, a new type of scattering processes in the contours controls the underlying physics of localization in the random magnetic field system. In addition, we investigate the role of vortices in governing the metal-insulator transition and propose a renormalization-group diagram for the system under study.Comment: 17 pages, 16 figures; Figs. 1, 7, 9, and 10 have been reduced in quality for e-submissio

Super universality of the quantum Hall effect and the "large NN picture" of the ϑ\vartheta angle

It is shown that the "massless chiral edge excitations" are an integral and universal aspect of the low energy dynamics of the $\vartheta$ vacuum that has historically gone unnoticed. Within the $SU(M+N)/S(U(M) \times U(N))$ non-linear sigma model we introduce an effective theory of "edge excitations" that fundamentally explains the quantum Hall effect. In sharp contrast to the common beliefs in the field our results indicate that this macroscopic quantization phenomenon is, in fact, a {\em super universal} strong coupling feature of the $\vartheta$ angle with the replica limit $M=N=0$ only playing a role of secondary importance. To demonstrate super universality we revisit the large $N$ expansion of the $CP^{N-1}$ model. We obtain, for the first time, explicit scaling results for the quantum Hall effect including quantum criticality of the quantum Hall plateau transition. Consequently a scaling diagram is obtained describing the cross-over between the weak coupling "instanton phase" and the strong coupling "quantum Hall phase" of the large $N$ theory. Our results are in accordance with the "instanton picture" of the $\vartheta$ angle but fundamentally invalidate all the ideas, expectations and conjectures that are based on the historical "large $N$ picture."Comment: 40 pages, 9 figure

Parkin-deficient Mice Exhibit Nigrostriatal Deficits but not Loss of Dopaminergic Neurons

Loss-of-function mutations in parkin are the major cause of early-onset familial Parkinson's disease. To investigate the pathogenic mechanism by which loss of parkin function causes Parkinson's disease, we generated a mouse model bearing a germline disruption in parkin. Parkin-/- mice are viable and exhibit grossly normal brain morphology. Quantitative in vivo microdialysis revealed an increase in extracellular dopamine concentration in the striatum of parkin-/- mice. Intracellular recordings of medium-sized striatal spiny neurons showed that greater currents are required to induce synaptic responses, suggesting a reduction in synaptic excitability in the absence of parkin. Furthermore, parkin-/- mice exhibit deficits in behavioral paradigms sensitive to dysfunction of the nigrostriatal pathway. The number of dopaminergic neurons in the substantia nigra of parkin-/- mice, however, is normal up to the age of 24 months, in contrast to the substantial loss of nigral neurons characteristic of Parkinson's disease. Steady-state levels of CDCrel-1, synphilin-1, and α-synuclein, which were identified previously as substrates of the E3 ubiquitin ligase activity of parkin, are unaltered in parkin-/- brains. Together these findings provide the first evidence for a novel role of parkin in dopamine regulation and nigrostriatal function, and a non-essential role of parkin in the survival of nigral neurons in mice

Measurement of the Running of the Electromagnetic Coupling at Large Momentum-Transfer at LEP

The evolution of the electromagnetic coupling, alpha, in the momentum-transfer range 1800GeV^2 < -Q^2 < 21600GeV^2 is studied with about 40000 Bhabha-scattering events collected with the L3 detector at LEP at centre-of-mass energies 189-209GeV. The running of alpha is parametrised as: alpha(Q^2) = alpha_0/(1-C Delta alpha(Q^2)), where alpha_0=\alpha(Q^2=0) is the fine-structure constant and C=1 corresponds to the evolution expected in QED. A fit to the differential cross section of the e+e- ->e+e- process for scattering angles in the range |cos theta|<0.9 excludes the hypothesis of a constant value of alpha, C=0, and validates the QED prediction with the result: C = 1.05 +/- 0.07 +/- 0.14, where the first uncertainty is statistical and the second systematic

Modeling Vortex Swarming In Daphnia

Based on experimental observations in \textit{Daphnia}, we introduce an agent-based model for the motion of single and swarms of animals. Each agent is described by a stochastic equation that also considers the conditions for active biological motion. An environmental potential further reflects local conditions for \textit{Daphnia}, such as attraction to light sources. This model is sufficient to describe the observed cycling behavior of single \textit{Daphnia}. To simulate vortex swarming of many \textit{Daphnia}, i.e. the collective rotation of the swarm in one direction, we extend the model by considering avoidance of collisions. Two different ansatzes to model such a behavior are developed and compared. By means of computer simulations of a multi-agent system we show that local avoidance - as a special form of asymmetric repulsion between animals - leads to the emergence of a vortex swarm. The transition from uncorrelated rotation of single agents to the vortex swarming as a function of the swarm size is investigated. Eventually, some evidence of avoidance behavior in \textit{Daphnia} is provided by comparing experimental and simulation results for two animals.Comment: 24 pages including 11 multi-part figs. Major revisions compared to version 1, new results on transition from uncorrelated rotation to vortex swarming. Extended discussion. For related publications see http://www.sg.ethz.ch/people/scfrank/Publication

Immigration and Internal Migration 'Flight' from US Metropolitan Areas: Toward a New Demographic Balkanisation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68704/2/10.1080_00420989550012861.pd