“Malignant” Perivascular Epithelioid Cell Neoplasm: Risk Stratification and Treatment Strategies

Purpose. Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors characterized by a myomelanocytic phenotype, and PEComas occurring in “nonclassic” anatomic distributions are known as perivascular epithelioid cell tumor not otherwise specified (PEComa-NOS). This review aims to compile and analyze cases of PEComa-NOS in an effort to better define their natural history. Design. We evaluated all 234 cases of PEComa-NOS reported in the English literature, extracting information regarding diagnostic features, treatment approaches, and outcomes. Multivariate analysis of a number of variables evaluable on pathologic review was performed to refine preexisting risk stratification criteria. Outcomes for patients receiving nonsurgical treatment are also reported. Results. Primary tumor size ≥5 cm (P = 0.02) and a high (1/50 HPF) mitotic rate (P < 0.0001) were the only factors significantly associated with recurrence following surgical resection. Cytotoxic chemotherapy and radiation therapy have shown little benefit in treating PEComa-NOS; mTOR inhibition is emerging as a treatment option. Conclusion. Progress has been made in understanding the natural history and molecular biology of PEComa-NOS. This review further clarifies risk of recurrence in this disease, allowing clinicians to better risk stratify patients. Further work should focus on applying this knowledge to making treatment decisions for patients with this disease

Colorectal cancer patients with liver metastases and severe hyperbilirubinemia: A consecutive series that explores the benefits and risks of chemotherapy

Tamana Walia, J Fernando Quevedo, Timothy J Hobday, Gary Croghan, Aminah JatoiDivision of Medical Oncology, Rochester, MN, USABackground: Do colorectal cancer patients with hyperbilirubinemia and liver metastases benefit from chemotherapy?Methods/Results: This study entailed a review of 3,019 consecutive patients with colorectal cancer. Within this cohort, 20 met the study&amp;rsquo;s a priori selection criteria, which included a new diagnosis of colorectal cancer, no prior therapy, and a total bilirubin of &amp;ge;3.0 mg/dL. All 20 patients had liver metastases, and as a whole the group had a median serum bilirubin of 6.4 mg/dL (range 3.1, 28 mg/dL). Six patients received chemotherapy with an oxaliplatin-containing regimen, and four subsequently sustained a drop in their bilirubin. In one instance, a drop from 27.2 to 2.5 mg/dL occurred. These six patients lived a median of 71 days (range 23+, 283 days), but one treatment-related death occurred. In contrast, patients who received only supportive care lived a median of 28 days.Conclusion: Chemotherapy appears to provide modest benefit to newly diagnosed colorectal cancer patients with severe hyperbilirubinemia.Keywords: colorectal cancer, liver metastases, hyperbilirubinemia, chemotherapy, oxaliplati

Fitting the Phenomenological MSSM

We perform a global Bayesian fit of the phenomenological minimal supersymmetric standard model (pMSSM) to current indirect collider and dark matter data. The pMSSM contains the most relevant 25 weak-scale MSSM parameters, which are simultaneously fit using `nested sampling' Monte Carlo techniques in more than 15 years of CPU time. We calculate the Bayesian evidence for the pMSSM and constrain its parameters and observables in the context of two widely different, but reasonable, priors to determine which inferences are robust. We make inferences about sparticle masses, the sign of the $\mu$ parameter, the amount of fine tuning, dark matter properties and the prospects for direct dark matter detection without assuming a restrictive high-scale supersymmetry breaking model. We find the inferred lightest CP-even Higgs boson mass as an example of an approximately prior independent observable. This analysis constitutes the first statistically convergent pMSSM global fit to all current data.Comment: Added references, paragraph on fine-tunin

TeV-Scale Z' Bosons from D-branes

Generic D-brane string models of particle physics predict the existence of extra U(1) gauge symmetries beyond hypercharge. These symmetries are not of the E_6 class but rather include the gauging of Baryon and Lepton numbers as well as certain Peccei-Quinn-like symmetries. Some of the U(1)'s have triangle anomalies, but they are cancelled by a Green-Schwarz mechanism. The corresponding gauge bosons typically acquire a mass of order the string scale M_S by combining with two-index antisymmetric fields coming from the closed string sector of the theory. We argue that in string models with a low string scale M_S proportional to 1-10 TeV, the presence of these generic U(1)'s may be amenable to experimental test. Present constraints from electroweak precision data already set important bounds on the mass of these extra gauge bosons. In particular, for large classes of models, rho-parameter constraints imply M_S >= 1.5 TeV. In the present scheme some fraction of the experimentally measured Z^0 mass would be due not to the Higgs mechanism, but rather to the mixing with these closed string fields. We give explicit formulae for recently constructed classes of intersecting D6- and D5-brane models yielding the Standard Model (SM) fermion spectrum.Comment: 46 pages, LaTeX, JHEP.cls, 21 Figures. minor correction

Branonium

We study the bound states of brane/antibrane systems by examining the motion of a probe antibrane moving in the background fields of N source branes. The classical system resembles the point-particle central force problem, and the orbits can be solved by quadrature. Generically the antibrane has orbits which are not closed on themselves. An important special case occurs for some Dp-branes moving in three transverse dimensions, in which case the orbits may be obtained in closed form, giving the standard conic sections but with a nonstandard time evolution along the orbit. Somewhat surprisingly, in this case the resulting elliptical orbits are exact solutions, and do not simply apply in the limit of asymptotically-large separation or non-relativistic velocities. The orbits eventually decay through the radiation of massless modes into the bulk and onto the branes, and we estimate this decay time. Applications of these orbits to cosmology are discussed in a companion paper.Comment: 34 pages, LaTeX, 4 figures, uses JHEP

Astrophysical and Cosmological Implications of Large Volume String Compactifications

We study the spectrum, couplings and cosmological and astrophysical implications of the moduli fields for the class of Calabi-Yau IIB string compactifications for which moduli stabilisation leads to an exponentially large volume V ~ 10^{15} l_s^6 and an intermediate string scale m_s ~ 10^{11}GeV, with TeV-scale observable supersymmetry breaking. All K\"ahler moduli except for the overall volume are heavier than the susy breaking scale, with m ~ ln(M_P/m_{3/2}) m_{3/2} ~ (\ln(M_P/m_{3/2}))^2 m_{susy} ~ 500 TeV and, contrary to standard expectations, have matter couplings suppressed only by the string scale rather than the Planck scale. These decay to matter early in the history of the universe, with a reheat temperature T ~ 10^7 GeV, and are free from the cosmological moduli problem (CMP). The heavy moduli have a branching ratio to gravitino pairs of 10^{-30} and do not suffer from the gravitino overproduction problem. The overall volume modulus is a distinctive feature of these models and is an M_{planck}-coupled scalar of mass m ~ 1 MeV and subject to the CMP. A period of thermal inflation can help relax this problem. This field has a lifetime ~ 10^{24}s and can contribute to dark matter. It may be detected through its decays to 2\gamma or e^+e^-. If accessible the e^+e^- decay mode dominates, with Br(\chi \to 2 \gamma) suppressed by a factor (ln(M_P/m_{3/2}))^2. We consider the potential for detection of this field through different astrophysical sources and find that the observed gamma-ray background constrains \Omega_{\chi} <~ 10^{-4}. The decays of this field may generate the 511 keV emission line from the galactic centre observed by INTEGRAL/SPI.Comment: 31 pages, 2 figures; v2. refs adde

SUSY Breaking and Moduli Stabilization from Fluxes in Gauged 6D Supergravity

We construct the 4D N=1 supergravity which describes the low-energy limit of 6D supergravity compactified on a sphere with a monopole background a la Salam and Sezgin. This provides a simple setting sharing the main properties of realistic string compactifications such as flat 4D spacetime, chiral fermions and N=1 supersymmetry as well as Fayet-Iliopoulos terms induced by the Green-Schwarz mechanism. The matter content of the resulting theory is a supersymmetric SO(3)xU(1) gauge model with two chiral multiplets, S and T. The expectation value of T is fixed by the classical potential, and S describes a flat direction to all orders in perturbation theory. We consider possible perturbative corrections to the Kahler potential in inverse powers of $Re S$ and $Re T$, and find that under certain circumstances, and when taken together with low-energy gaugino condensation, these can lift the degeneracy of the flat direction for $Re S$. The resulting vacuum breaks supersymmetry at moderately low energies in comparison with the compactification scale, with positive cosmological constant. It is argued that the 6D model might itself be obtained from string compactifications, giving rise to realistic string compactifications on non Ricci flat manifolds. Possible phenomenological and cosmological applications are briefly discussed.Comment: 32 pages, 2 figures. Uses JHEP3.cls. References fixed and updated, some minor typos fixed. Corrected minor error concerning Kaluza-Klein scales. Results remain unchange

Brane-Antibrane Inflation in Orbifold and Orientifold Models

We analyse the cosmological implications of brane-antibrane systems in string-theoretic orbifold and orientifold models. In a class of realistic models, consistency conditions require branes and antibranes to be stuck at different fixed points, and so their mutual attraction generates a potential for one of the radii of the underlying torus or the 4D string dilaton. Assuming that all other moduli have been fixed by string effects, we find that this potential leads naturally to a period of cosmic inflation with the radion or dilaton field as the inflaton. The slow-roll conditions are satisfied more generically than if the branes were free to move within the space. The appearance of tachyon fields at certain points in moduli space indicates the onset of phase transitions to different non-BPS brane systems, providing ways of ending inflation and reheating the corresponding observable brane universe. In each case we find relations between the inflationary parameters and the string scale to get the correct spectrum of density perturbations. In some examples the small numbers required as inputs are no smaller than 0.01, and are the same small quantities which are required to explain the gauge hierarchy.Comment: 30 pages, 2 figures. Substantial changes on version 1. New cosmological scenarios proposed including the dilaton as the inflaton. Main conclusions unchange