Atrioventricular canal defect and genetic syndromes: the unifying role of sonic hedgehog

The atrioventricular canal defect (AVCD) is a congenital heart defect (CHD) frequently associated with extracardiac anomalies (75%). Previous observations from a personal series of patients with AVCD and "polydactyly syndromes" showed that the distinct morphology and combination of AVCD features in some of these syndromes is reminiscent of the cardiac phenotype found in heterotaxy, a malformation complex previously associated with functional cilia abnormalities and aberrant Hedgehog (Hh) signaling. Hh signaling coordinates multiple aspects of left-right lateralization and cardiovascular growth. Being active at the venous pole the secondary heart field (SHF) is essential for normal development of dorsal mesenchymal protrusion and AVCD formation and septation. Experimental data show that perturbations of different components of the Hh pathway can lead to developmental errors presenting with partially overlapping manifestations and AVCD as a common denominator. We review the potential role of Hh signaling in the pathogenesis of AVCD in different genetic disorders. AVCD can be viewed as part of a "developmental field," according to the concept that malformations can be due to defects in signal transduction cascades or pathways, as morphogenetic units which may be altered by Mendelian mutations, aneuploidies, and environmental causes

f(R)f(R) theory and geometric origin of the dark sector in Horava-Lifshitz gravity

Inclusion of $f(R)$ term in the action of Horava-Lifshitz quantum gravity with projectability but without detailed balance condition is investigated, where $R$ denotes the 3-spatial dimensional Ricci scalar. Conditions for the spin-0 graviton to be free of ghosts and instability are studied. The requirement that the theory reduce to general relativity in the IR makes the scalar mode unstable in the Minkowski background but stable in the de Sitter. It is remarkable that the dark sector, dark matter and dark energy, of the universe has a naturally geometric origin in such a setup. Bouncing universes can also be constructed. Scalar perturbations in the FRW backgrounds with non-zero curvature are presented.Comment: Mod. Phys. Lett. A26, 387-398 (2011

Detailed balance in Horava-Lifshitz gravity

We study Horava-Lifshitz gravity in the presence of a scalar field. When the detailed balance condition is implemented, a new term in the gravitational sector is added in order to maintain ultraviolet stability. The four-dimensional theory is of a scalar-tensor type with a positive cosmological constant and gravity is nonminimally coupled with the scalar and its gradient terms. The scalar field has a double-well potential and, if required to play the role of the inflation, can produce a scale-invariant spectrum. The total action is rather complicated and there is no analog of the Einstein frame where Lorentz invariance is recovered in the infrared. For these reasons it may be necessary to abandon detailed balance. We comment on open problems and future directions in anisotropic critical models of gravity.Comment: 10 pages. v2: discussion expanded and improved, section on generalizations added, typos corrected, references added, conclusions unchange

The Black Hole and Cosmological Solutions in IR modified Horava Gravity

Recently Horava proposed a renormalizable gravity theory in four dimensions which reduces to Einstein gravity with a non-vanishing cosmological constant in IR but with improved UV behaviors. Here, I study an IR modification which breaks "softly" the detailed balance condition in Horava model and allows the asymptotically flat limit as well. I obtain the black hole and cosmological solutions for "arbitrary" cosmological constant that represent the analogs of the standard Schwartzschild-(A)dS solutions which can be asymptotically (A)dS as well as flat and I discuss some thermodynamical properties. I also obtain solutions for FRW metric with an arbitrary cosmological constant. I study its implication to the dark energy and find that it seems to be consistent with current observational data.Comment: Footnote 5 about the the very meaning of the horizons and Hawking temperature is added; Accepted in JHE

Horava-Lifshitz Cosmology: A Review

This article reviews basic construction and cosmological implications of a power-counting renormalizable theory of gravitation recently proposed by Horava. We explain that (i) at low energy this theory does not exactly recover general relativity but instead mimic general relativity plus dark matter; that (ii) higher spatial curvature terms allow bouncing and cyclic universes as regular solutions; and that (iii) the anisotropic scaling with the dynamical critical exponent z=3 solves the horizon problem and leads to scale-invariant cosmological perturbations even without inflation. We also comment on issues related to an extra scalar degree of freedom called scalar graviton. In particular, for spherically-symmetric, static, vacuum configurations we prove non-perturbative continuity of the lambda->1+0 limit, where lambda is a parameter in the kinetic action and general relativity has the value lambda=1. We also derive the condition under which linear instability of the scalar graviton does not show up.Comment: 28 pages, invited review for CQG; version to be published (v2

Lessons Learned from the Implementation of a Medically Enhanced Residential Treatment (Mert) Model Integrating Intravenous Antibiotics and Residential Addiction Treatment

BACKGROUND: Hospitalizations for severe infections associated with substance use disorder (SUD) are increasing. People with SUD often remain hospitalized for many weeks instead of completing intravenous antibiotics at home; often, they are denied skilled nursing facility admission. Residential SUD treatment facilities are not equipped to administer intravenous antibiotics. We developed a medically enhanced residential treatment (MERT) model integrating residential SUD treatment and long-term IV antibiotics as part of a broader hospital-based addiction medicine service. MERT had low recruitment and retention, and ended after six months. The goal of this study was to describe the feasibility and acceptability of MERT, to understand implementation factors, and explore lessons learned. METHODS: We conducted a mixed-methods evaluation. We included all potentially eligible MERT patients, defined by those needing ≥2 weeks of intravenous antibiotics discharged from February 1 to August 1, 2016. We used chart review to identify diagnoses, antibiotic treatment location, and number of recommended and actual IV antibiotic-days completed. We audiorecorded and transcribed key informant interviews with patients and staff. We conducted an ethnographic analysis of interview transcripts and implementation field notes. RESULTS: Of the 45 patients needing long-term intravenous antibiotics, 18 were ineligible and 20 declined MERT. 7 enrolled in MERT and three completed their recommended intravenous antibiotic course. MERT recruitment barriers included patient ambivalence towards residential treatment, wanting to prioritize physical health needs, and fears of untreated pain in residential. MERT retention barriers included high demands of residential treatment, restrictive practices due to PICC lines, and perceptions by staff and other residents that MERT patients “stood out” as “different.” Despite the challenges, key informants felt MERT was a positive construct. CONCLUSIONS: Though MERT had many possible advantages; it proved more challenging to implement than anticipated. Our lessons may be applicable to future models integrating posthospital intravenous antibiotics and SUD care

Horava-Lifshitz modifications of the Casimir effect

We study the modifications induced by spacetime anisotropy on the Casimir effect in the case of two parallel plates. Nonperturbative and perturbative regimes are analyzed. In the first case the Casimir force either vanishes or it reverses its direction which, in any case, makes the proposal untenable. On the other hand, the perturbative model enables us to incorporate appropriately the effects of spacetime anisotropy.Comment: 6 pages, revtex

Dark energy generated from a (super)string effective action with higher order curvature corrections and a dynamical dilaton

We investigate the possibility of a dark energy universe emerging from an action with higher-order string loop corrections to Einstein gravity in the presence of a massless dilaton. These curvature corrections (up to $R^4$ order) are different depending upon the type of (super)string model which is considered. We find in fact that Type II, heterotic, and bosonic strings respond differently to dark energy. A dark energy solution is shown to exist in the case of the bosonic string, while the other two theories do not lead to realistic dark energy universes. Detailed analysis of the dynamical stability of the de-Sitter solution is presented for the case of a bosonic string. A general prescription for the construction of a de-Sitter solution for the low-energy (super)string effective action is also indicated. Beyond the low-energy (super)string effective action, when the higher-curvature correction coefficients depend on the dilaton, the reconstruction of the theory from the universe expansion history is done with a corresponding prescription for the scalar potentials.Comment: 15 pages, 7 eps figures, minor corrections, published versio

Thermodynamical Laws in Horava-Lifshitz Gravity

In this work, we have investigated the validity of GSL of thermodynamics in a universe (open, closed and flat) governed by Ho$\check{\text r}$ava-Lifshitz gravity. If the universe contains barotropic fluid the corresponding solutions have been obtained. The validity of GSL have been examined by two approaches: (i) robust approach and (ii) effective approach. In robust approach, we have considered the universe contains only matter fluid and the effect of the gravitational sector of HL gravity was incorporated through the modified black hole entropy on the horizon. Effective approach is that all extra information of HL gravity into an effective dark energy fluid and so we consider the universe contains matter fluid plus this effective fluid. This approach is essentially same as the Einstein's gravity theory. The general prescription for validity of GSL have been discussed. Graphically we have shown that the GSL may be satisfied for open, closed and flat universe on the different horizons with different conditions.Comment: 7 latex pages, 7 figure

Cosmological perturbations in a healthy extension of Horava gravity

In Horava's theory of gravity, Lorentz symmetry is broken in exchange for renormalizability, but the original theory has been argued to be plagued with problems associated with a new scalar mode stemming from the very breaking of Lorentz symmetry. Recently, Blas, Pujolas, and Sibiryakov have proposed a healthy extension of Horava gravity, in which the behavior of the scalar mode is improved. In this paper, we study scalar modes of cosmological perturbations in extended Horava gravity. The evolution of metric and density perturbations is addressed analytically and numerically. It is shown that for vanishing non-adiabatic pressure of matter the large scale evolution of cosmological perturbations converges to that described by a single constant, $\zeta$, which is an analog of a curvature perturbation on the uniform-density slicing commonly used in usual gravitational theories. The subsequent evolution is thus determined completely by the value of $\zeta$.Comment: 10 pages, 4 figures; v2: published versio