A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure

Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6–11.0 years) and controls (n = 16, 9.5–11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent

Feasibility and Acceptability of Maternal Choline Supplementation in Heavy Drinking Pregnant Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Choline, an essential nutrient, serves as a methyl-group donor for DNA methylation and is a constituent of the neurotransmitter acetylcholine and a precursor to major components of cell membranes. Findings from animal studies suggest that choline supplementation during pregnancy can mitigate adverse effects of prenatal alcohol exposure on growth and neurocognitive function. We conducted a randomized, double-blind exploratory trial to examine feasibility and acceptability of a choline supplementation intervention during pregnancy. Methods: Seventy heavy drinkers, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of 2 g of choline or a placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. Adherence was assessed by collecting used and unused drink packets on a monthly basis and tabulating the number used. Side effects were assessed in monthly interviews. Blood samples obtained at enrollment and at 4 and 12 weeks after randomization were assayed for plasma choline concentration. Results: Adherence was good-to-excellent (median doses taken = 74.0%; interquartile range = 53.9 to 88.7%) and was not related to a range of sociodemographic characteristics or to alcohol consumption ascertained using a timeline follow-back interview. By 4 weeks, plasma choline concentrations were significantly higher in the choline supplementation than the placebo arm, and this group difference continued to be evident at 12 weeks. The only side effect was a small increase in nausea/dyspepsia. No effects were seen for diarrhea, vomiting, muscle stiffness, blood pressure, or body odor changes. Conclusions: This study demonstrated that a choline supplementation program with very heavy drinkers during pregnancy is feasible even among highly disadvantaged, poorly educated women. The broad acceptability of this intervention is indicated by our finding that adherence was not related to maternal education, intellectual function, depression, nutritional status, or alcohol use

Constrained Gauge Fields from Spontaneous Lorentz Violation

Spontaneous Lorentz violation realized through a nonlinear vector field constraint of the type $A_{\mu}A^{\mu}=M^{2}$ ($M$ is the proposed scale for Lorentz violation) is shown to generate massless vector Goldstone bosons, gauging the starting global internal symmetries in arbitrary relativistically invariant theories. The gauge invariance appears in essence as a necessary condition for these bosons not to be superfluously restricted in degrees of freedom, apart from the constraint due to which the true vacuum in a theory is chosen by the Lorentz violation. In the Abelian symmetry case the only possible theory proves to be QED with a massless vector Goldstone boson naturally associated with the photon, while the non-Abelian symmetry case results in a conventional Yang-Mills theory. These theories, both Abelian and non-Abelian, look essentially nonlinear and contain particular Lorentz (and $CPT$) violating couplings when expressed in terms of the pure Goldstone vector modes. However, they do not lead to physical Lorentz violation due to the simultaneously generated gauge invariance.Comment: 15 pages, minor corrections, version to be published in Nucl. Phys.

Dynamics of Enceladus and Dione inside the 2:1 Mean-Motion Resonance under Tidal Dissipation

In a previous work (Callegari and Yokoyama 2007, Celest. Mech. Dyn. Astr. vol. 98), the main features of the motion of the pair Enceladus-Dione were analyzed in the frozen regime, i.e., without considering the tidal evolution. Here, the results of a great deal of numerical simulations of a pair of satellites similar to Enceladus and Dione crossing the 2:1 mean-motion resonance are shown. The resonance crossing is modeled with a linear tidal theory, considering a two-degrees-of-freedom model written in the framework of the general three-body planar problem. The main regimes of motion of the system during the passage through resonance are studied in detail. We discuss our results comparing them with classical scenarios of tidal evolution of the system. We show new scenarios of evolution of the Enceladus-Dione system through resonance not shown in previous approaches of the problem.Comment: 36 pages, 12 figures. Accepted in Celestial Mechanics and Dynamical Astronom

Spontaneously Generated Tensor Field Gravity

An arbitrary local theory of a symmetric two-tensor field $H_{\mu \nu}$ in Minkowski spacetime is considered, in which the equations of motion are required to be compatible with a nonlinear length-fixing constraint $H_{\mu \nu}^{2}=\pm M^{2}$ leading to spontaneous Lorentz invariance violation, SLIV ($M$ is the proposed scale for SLIV). Allowing the parameters in the Lagrangian to be adjusted so as to be consistent with this constraint, the theory turns out to correspond to linearized general relativity in the weak field approximation, while some of the massless tensor Goldstone modes appearing through SLIV are naturally collected in the physical graviton. In essence the underlying diffeomophism invariance emerges as a necessary condition for the tensor field $H_{\mu \nu}$ not to be superfluously restricted in degrees of freedom, apart from the constraint due to which the true vacuum in the theory is chosen by SLIV. The emergent theory appears essentially nonlinear, when expressed in terms of the pure Goldstone tensor modes and contains a plethora of new Lorentz and $CPT$ violating couplings. However, these couplings do not lead to physical Lorentz violation once this tensor field gravity is properly extended to conventional general relativity.Comment: 27 pages, published version, to appear in Nuclear Physics

Influence of the coorbital resonance on the rotation of the Trojan satellites of Saturn

The Cassini spacecraft collects high resolution images of the saturnian satellites and reveals the surface of these new worlds. The shape and rotation of the satellites can be determined from the Cassini Imaging Science Subsystem data, employing limb coordinates and stereogrammetric control points. This is the case for Epimetheus (Tiscareno et al. 2009) that opens elaboration of new rotational models (Tiscareno et al. 2009; Noyelles 2010; Robutel et al. 2011). Especially, Epimetheus is characterized by its horseshoe shape orbit and the presence of the swap is essential to introduce explicitly into rotational models. During its journey in the saturnian system, Cassini spacecraft accumulates the observational data of the other satellites and it will be possible to determine the rotational parameters of several of them. To prepare these future observations, we built rotational models of the coorbital (also called Trojan) satellites Telesto, Calypso, Helene, and Polydeuces, in addition to Janus and Epimetheus. Indeed, Telesto and Calypso orbit around the L_4 and L_5 Lagrange points of Saturn-Tethys while Helene and Polydeuces are coorbital of Dione. The goal of this study is to understand how the departure from the Keplerian motion induced by the perturbations of the coorbital body, influences the rotation of these satellites. To this aim, we introduce explicitly the perturbation in the rotational equations by using the formalism developed by Erdi (1977) to represent the coorbital motions, and so we describe the rotational motion of the coorbitals, Janus and Epimetheus included, in compact form

Modified Gravity via Spontaneous Symmetry Breaking

We construct effective field theories in which gravity is modified via spontaneous breaking of local Lorentz invariance. This is a gravitational analogue of the Higgs mechanism. These theories possess additional graviton modes and modified dispersion relations. They are manifestly well-behaved in the UV and free of discontinuities of the van Dam-Veltman-Zakharov type, ensuring compatibility with standard tests of gravity. They may have important phenomenological effects on large distance scales, offering an alternative to dark energy. For the case in which the symmetry is broken by a vector field with the wrong sign mass term, we identify four massless graviton modes (all with positive-definite norm for a suitable choice of a parameter) and show the absence of the discontinuity.Comment: 5 pages; revised versio

Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and cognitive function. Methods: Sixty-nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months. Results: Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory. Conclusions: This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory

Background Dependent Lorentz Violation: Natural Solutions to the Theoretical Challenges of the OPERA Experiment

To explain both the OPERA experiment and all the known phenomenological constraints/observations on Lorentz violation, the Background Dependent Lorentz Violation (BDLV) has been proposed. We study the BDLV in a model independent way, and conjecture that there may exist a "Dream Special Relativity Theory", where all the Standard Model (SM) particles can be subluminal due to the background effects. Assuming that the Lorentz violation on the Earth is much larger than those on the interstellar scale, we automatically escape all the astrophysical constraints on Lorentz violation. For the BDLV from the effective field theory, we present a simple model and discuss the possible solutions to the theoretical challenges of the OPERA experiment such as the Bremsstrahlung effects for muon neutrinos and the pion decays. Also, we address the Lorentz violation constraints from the LEP and KamLAMD experiments. For the BDLV from the Type IIB string theory with D3-branes and D7-branes, we point out that the D3-branes are flavour blind, and all the SM particles are the conventional particles as in the traditional SM when they do not interact with the D3-branes. Thus, we not only can naturally avoid all the known phenomenological constraints on Lorentz violation, but also can naturally explain all the theoretical challenges. Interestingly, the energy dependent photon velocities may be tested at the experiments.Comment: RevTex4, 14 pages, minor corrections, references adde

A cell cycle model for somitogenesis: mathematical formulation and numerical simulation

After many years of research, the mechanisms that generate a periodic pattern of repeated elements (somites) along the length of the embryonic body axis is still one of the major unresolved problems in developmental biology. Here we present a mathematical formulation of the cell cycle model for somitogenesis proposed in Development105 (1989), 119–130. Somite precursor cells in the node are asynchronous, and therefore, as a population, generate continuously pre-somite cells which enter the segmental plate. The model makes the hypothesis that there exists a time window within the cell cycle, making up one-seventh of the cycle, which gates the pre-somite cells so that they make somites discretely, seven per cycle. We show that the model can indeed account for the spatiotemporal patterning of somite formation during normal development as well as the periodic abnormalities produced by heat shock treatment. We also relate the model to recent molecular data on the process of somite formation