Gamma oscillatory activity in vitro: a model system to assess pathophysiological mechanisms of comorbidity between autism and epilepsy.

Autism spectrum disorder (ASD) and temporal lobe epilepsy exhibit remarkable comorbidity, but for reasons not clearly understood. To reveal a common pathophysiological mechanism, we here describe and characterize an in vitro epileptiform activity in the rat hippocampus that exhibits common features with in vivo activity in rodent ASD models. We discovered the development of this activity in the CA1 region of horizontal slices after prolonged interictal-like epileptiform activity in the CA3 region that was provoked by incubation in high potassium artificial cerebrospinal fluid. The CA1 epileptiform bursts were insensitive to blockers of glutamatergic transmission, and were carried by synaptic as well as extrasynaptic, tonically activated gamma-aminobutyric acid type A (GABA(A)) receptors. The bursts bear resemblance to in vivo gamma-oscillatory activity found in rat ASD models with respect to their gamma frequency spectrum, their origin (in the CA1), and their sensitivity to blockers of cation-chloride pumps (NKCC1 and KCC2), as well as to oxytocin. Considering this bursting activity as an in vitro model for studying comorbidity between epilepsy and ASD may help to disentangle the intricate interactions that underlie the comorbidity between both diseases and suggests that extrasynaptic tonic GABAergic transmission could represent a potential target for ASD

Neutrinos in 5D SO(10) Unification

We study neutrino physics in a 5D supersymmetric SO(10) GUT. We analyze several different choices for realizing the See-Saw mechanism. We find that the "natural" scale for the Majorana mass of right-handed neutrinos depends critically on whether the right-handed neutrinos are located in the bulk or localized on a brane. In the former case, the effective Majorana mass is "naturally" of order the compactification scale, about 10^{14} GeV. Note, this is the value necessary for obtaining a light tau neutrino mass approximately 10^{-2} eV which, within the context of hierarchical neutrino masses, is the right order of magnitude to explain atmospheric neutrino oscillations. On the other-hand when the right-handed neutrino is localized on the brane, the effective Majorana mass is typically larger than the compactification scale. Nevertheless with small parameters of order 1/10 - 1/30, an effective Majorana mass of order 10^{14} GeV can be accommodated. We also discuss the constraints on model building resulting from the different scenarios for locating the right-handed neutrinos.Comment: 24 page

Seesaw Extended MSSM and Anomaly Mediation without Tachyonic Sleptons

Superconformal anomalies provide an elegant and economical way to understand the soft breaking parameters in SUSY models; however, implementing them leads to the several undesirable features including: tachyonic sleptons and electroweak symmetry breaking problems in both the MSSM and the NMSSM. Since these two theories also have the additonal problem of massless neutrinos, we have reconsidered the AMSB problems in a class of models that extends the NMSSM to explain small neutrino masses via the seesaw mechanism. In a recent paper, we showed that for a class of minimal left-right extensions, a built-in mechanism exists which naturally solves the tachyonic slepton problem and provides new alternatives to the MSSM that also have automatic R-parity conservation. In this paper, we discuss how electroweak symmetry breaking arises in this model through an NMSSM-like low energy theory with a singlet VEV, induced by the structure of the left-right extension and of the right magnitude. We then study the phenomenological issues and find: the LSP is an Higgsino-wino mix, new phenomenology for chargino decays to the LSP, degenerate same generation sleptons and a potential for a mild squark-slepton degeneracy. We also discuss possible collider signatures and the feasibility of dark matter in this model.Comment: 40 pages, 10 figures, 5 tables; v3: Added addendum and three new references; v4: Added reference that was inadvertently omitte

Can multi-TeV (top and other) squarks be natural in gauge mediation?

We investigate whether multi-TeV (1-3 TeV) squarks can be natural in models of gauge mediated SUSY breaking. The idea is that for some boundary condition of the scalar (Higgs and stop) masses, the Higgs (mass)$^2$, evaluated at the renormalization scale $\sim O(100)$ GeV, is not very sensitive to (boundary values of) the scalar masses (this has been called ``focussing'' in recent literature). Then, the stop masses can be multi-TeV without leading to fine-tuning in electroweak symmetry breaking. {\em Minimal} gauge mediation does {\em not} lead to this focussing (for all values of $\tan \beta$ and the messenger scale): the (boundary value of) the Higgs mass is too small compared to the stop masses. Also, in minimal gauge mediation, the gaugino masses are of the same order as the scalar masses so that multi-TeV scalars implies multi-TeV gauginos (especially gluino) leading to fine-tuning. We discuss ideas to {\em increase} the Higgs mass relative to the stop masses (so that focussing can be achieved) and also to {\em suppress} gaugino masses relative to scalar masses (or to modify the gaugino mass relations) in {\em non-minimal} models of gauge mediation -- then multi-TeV (top and other) squarks can be natural. Specific models of gauge mediation which incorporate these ideas and thus have squarks (and in some cases, the gluino) heavier than a TeV without resulting in fine-tuning are also studied and their collider signals are contrasted with those of other models which have multi-TeV squarks.Comment: LaTeX, 29 pages, 9 eps figures. Replacing an earlier version. In version 3, some references and a minor comment have been added and typos have been correcte

The Superpartner Spectrum of Gaugino Mediation

We compute the superpartner masses in a class of models with gaugino mediation (or no-scale) boundary conditions at a scale between the GUT and Planck scales. These models are compelling because they are simple, solve the supersymmetric flavor and CP problems, satisfy all constraints from colliders and cosmology, and predict the superpartner masses in terms of very few parameters. Our analysis includes the renormalization group evolution of the soft-breaking terms above the GUT scale. We show that the running above the GUT scale is largely model independent and find that a phenomenologically viable spectrum is obtained.Comment: 15 page

Quintessence from Shape Moduli

We show that shape moduli in sub-millimeter extra dimensional scenarios, addressing the gauge hierarchy problem, can dominate the energy density of the universe today. In our scenario, the volume of the extra dimensions is stabilized at a sufficiently high scale to avoid conflicts with nucleosynthesis and solar-system precision gravity experiments, while the shape moduli remain light but couple extremely weakly to brane-localized matter and easily avoid these bounds. Nonlocal effects in the bulk of the extra dimension generate a potential for the shape moduli. The potential has the right form and order of magnitude to account for the present day cosmic acceleration, in a way analogous to models of quintessence as a pseudo Nambu-Goldstone boson.Comment: 8 pages, 1 figur

The Gaugino Code

Gauginos might play a crucial role in the search for supersymmetry at the Large Hadron Collider (LHC). Mass predictions for gauginos are rather robust and often related to the values of the gauge couplings. We analyse the ratios of gaugino masses in the LHC energy range for various schemes of supersymmetry breakdown and mediation. Three distinct mass patterns emerge.Comment: 42 pages, Latex; a discussion of deflected anomaly mediation added, references adde

Precision Electroweak Data and Unification of Couplings in Warped Extra Dimensions

Warped extra dimensions allow a novel way of solving the hierarchy problem, with all fundamental mass parameters of the theory naturally of the order of the Planck scale. The observable value of the Higgs vacuum expectation value is red-shifted, due to the localization of the Higgs field in the extra dimension. It has been recently observed that, when the gauge fields propagate in the bulk, unification of the gauge couplings may be achieved. Moreover, the propagation of fermions in the bulk allows for a simple solution to potentially dangerous proton decay problems. However, bulk gauge fields and fermions pose a phenomenological challenge, since they tend to induce large corrections to the precision electroweak observables. In this article, we study in detail the effect of gauge and fermion fields propagating in the bulk in the presence of gauge brane kinetic terms compatible with gauge coupling unification, and we present ways of obtaining a consistent description of experimental data, while allowing values of the first Kaluza Klein mode masses of the order of a few TeV.Comment: 32 pages, 7 figures. References adde

Surgical management of giant pituitary neuroendocrine tumors: Meta-analysis and consensus statement on behalf of the EANS skull base section.

The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated. The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section. We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. 20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranial approaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases. After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy

Stable, Time-Dependent, Exact Solutions for Brane Models with a Bulk Scalar Field

We derive two classes of brane-world solutions arising in the presence of a bulk scalar field. For static field configurations, we adopt a time-dependent, factorizable metric ansatz that allows for radion stabilization. The solutions are characterized by a non-trivial warping along the extra dimension, even in the case of a vanishing bulk cosmological constant, and lead to a variety of inflationary, time-dependent solutions of the 3D scale factor on the brane. We also derive the constraints necessary for the stability of these solutions under time-dependent perturbations of the radion field, and we demonstrate the existence of phenomenologically interesting, stable solutions with a positive cosmological constant on the brane.Comment: 24 pages, latex, 4 eps figur