Quantifying the Impact of Altered Hemodynamics and Vascular Biomechanics to Changes in Structure and Function in Native and Corrected Aortic Coarctation

Coarctation of the aorta (CoA) is associated with substantial cardiovascular morbidities despite successful treatment through surgical or catheter-based intervention. Although specific mechanisms leading to these morbidities remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We used a novel animal model that facilitates quantification of CoA-induced hemodynamic and vascular biomechanics alterations and their impact on vascular structure and function, independent of genetic or confounding factors. Rabbits underwent thoracic CoA at 10 weeks of age (~9 human years) to induce a 20 mmHg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using subject-specific imaging and BP data at 32 weeks to quantify velocity, strain, and wall shear stress (WSS). Vascular structure and function were evaluated at proximal and distal locations by histology, immunohistochemistry, and myograph analysis. Results revealed proximal systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular remodeling, endothelial dysfunction proximally and distally, and increased stiffness and reduced active force response proximally. Corrected rabbits had reduced but significant medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of alleviated systolic and mean BP (~4 human years) after the suture dissolved. Proximal arteries of CoA and corrected groups demonstrated increased non-muscle myosin expression and decreased myosin heavy chain expression, and this dedifferentiation may influence vascular remodeling and aortic stiffening. CFD analysis of untreated CoA rabbits demonstrated significantly reduced WSS proximal to CoA and markedly elevated WSS distally due to the presence of a stenotic velocity jet. Results from corrected rabbits indicate the velocity jet may have persistent effects on hemodynamics, as WSS remained significantly reduced. These hemodynamic and morphological observations are consistent with alterations in human patients. Using these coupled imaging and experimental results, we may determine changes in structure and function specific to CoA and correction and how they are influenced by hemodynamics and vascular biomechanics. We are now poised to augment clinical treatment of CoA through several methods, including investigation of specific cellular mechanisms causing morbidity in CoA and the development of therapies to improve endothelial function and restore vascular stiffness

Natural Supersymmetry and Implications for Higgs physics

We re-analyze the LHC bounds on light third generation squarks in Natural Supersymmetry, where the sparticles have masses inversely proportional to their leading-log contributions to the electroweak symmetry breaking scale. Higgsinos are the lightest supersymmetric particles; top and bottom squarks are the next-to-lightest sparticles that decay into both neutral and charged Higgsinos with well-defined branching ratios determined by Yukawa couplings and kinematics. The Higgsinos are nearly degenerate in mass, once the bino and wino masses are taken to their natural (heavy) values. We consider three scenarios for the stop and sbottom masses: (I) $\tilde{t}_R$ is light, (II) $\tilde{t}_L$ and $\tilde{b}_L$ are light, and (III) $\tilde{t}_R$, $\tilde{t}_L$, and $\tilde{b}_L$ are light. Dedicated stop searches are currently sensitive to Scenarios II and III, but not Scenario I. Sbottom-motivated searches ($2 b + \rm{MET}$) impact both squark flavors due to \tilde{t} \ra b \charp_1 as well as \tilde{b} \ra b \neut_{1,2}, constraining Scenarios I and III with somewhat weaker constraints on Scenario II. The totality of these searches yield relatively strong constraints on Natural Supersymmetry. Two regions that remain are: (1) the "compressed wedge", where $(m_{\tilde{q}} - |\mu|)/m_{\tilde{q}} \ll 1$, and (2) the "kinematic limit" region, where m_{\tilde{q}} \gsim 600-750 GeV, at the kinematic limit of the LHC searches. We calculate the correlated predictions for Higgs physics, demonstrating that these regions lead to distinct predictions for the lightest Higgs couplings that are separable with \simeq 10% measurements. We show that these conclusions remain largely unchanged once the MSSM is extended to the NMSSM in order to naturally obtain a large enough mass for the lightest Higgs boson consistent with LHC data.Comment: 18 pages, 8 figure

Standard model explanation of a CDF dijet excess in Wjj

We demonstrate the recent observation of a peak in the dijet invariant mass of the Wjj signal observed by the CDF Collaboration can be explained as the same upward fluctuation observed by CDF in single-top-quark production. In general, both t-channel and s-channel single-top-quark production produce kinematically induced peaks in the dijet spectrum. Since CDF used a Monte Carlo simulation to subtract the single-top backgrounds instead of data, a peak in the dijet spectrum is expected. The D0 Collaboration has a small upward fluctuation in their published t-channel data; and hence we predict they would see at most a small peak in the dijet invariant mass spectrum of Wjj if they follow the same procedure as CDF.Comment: 3 pg., 2 figs, revtex, minor clarifications, to appear in Phys. Rev.