Hypothalamic Hamartomas: Evolving Understanding and Management

Hypothalamic hamartomas (HH) are rare, basilar developmental lesions with widespread comorbidities often associated with refractory epilepsy and encephalopathy. Imaging advances allow for early, even prenatal, detection. Genetic studies suggest mutations in GLI3 and other patterning genes are involved in HH pathogenesis. About 50-80% of children with HH suffer from severe rage and aggression and a majority of cases exhibit externalizing disorders. Behavioral disruption and intellectual disability may predate epilepsy. Neuropsychological, sleep and endocrine disorders are typical. The purpose of this paper is to provide a summary of the current understanding of HH, and to highlight opportunities for future research

Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1-Top3

double Holliday junction (dHJ) is a central intermediate of homologous recombination that can be processed to yield crossover or non-crossover recombination products. To preserve genomic integrity, cells possess mechanisms to avoid crossing over. We show that Saccharomyces cerevisiae Sgs1 and Top3 proteins are sufficient to migrate and disentangle a dHJ to produce exclusively non-crossover recombination products, in a reaction termed "dissolution." We show that Rmi1 stimulates dHJ dissolution at low Sgs1-Top3 protein concentrations, although it has no effect on the initial rate of Holliday junction (HJ) migration. Rmi1 serves to stimulate DNA decatenation, removing the last linkages between the repaired and template DNA molecules. Dissolution of a dHJ is a highly efficient and concerted alternative to nucleolytic resolution that prevents crossing over of chromosomes during recombinational DNA repair in mitotic cells and thereby contributes to genomic integrity

The Two Faces of Anomaly Mediation

Anomaly mediation is a ubiquitous source of supersymmetry (SUSY) breaking which appears in almost every theory of supergravity. In this paper, we show that anomaly mediation really consists of two physically distinct phenomena, which we dub "gravitino mediation" and "Kahler mediation". Gravitino mediation arises from minimally uplifting SUSY anti-de Sitter (AdS) space to Minkowski space, generating soft masses proportional to the gravitino mass. Kahler mediation arises when visible sector fields have linear couplings to SUSY breaking in the Kahler potential, generating soft masses proportional to beta function coefficients. In the literature, these two phenomena are lumped together under the name "anomaly mediation", but here we demonstrate that they can be physically disentangled by measuring associated couplings to the goldstino. In particular, we use the example of gaugino soft masses to show that gravitino mediation generates soft masses without corresponding goldstino couplings. This result naively violates the goldstino equivalence theorem but is in fact necessary for supercurrent conservation in AdS space. Since gravitino mediation persists even when the visible sector is sequestered from SUSY breaking, we can use the absence of goldstino couplings as an unambiguous definition of sequestering.Comment: 21 pages, 1 table; v2, references added, extended discussion in introduction and appendix; v3, JHEP versio

Towards multi-scale dynamics on the baryonic branch of Klebanov-Strassler

We construct explicitly a new class of backgrounds in type-IIB supergravity which generalize the baryonic branch of Klebanov-Strassler. We apply a solution-generating technique that, starting from a large class of solutions of the wrapped-D5 system, yields the new solutions, and then proceed to study in detail their properties, both in the IR and in the UV. We propose a simple intuitive field theory interpretation of the rotation procedure and of the meaning of our new solutions within the Papadopoulos-Tseytlin ansatz, in particular in relation to the duality cascade in the Klebanov-Strassler solution. The presence in the field theory of different VEVs for operators of dimensions 2, 3 and 6 suggests that this is an important step towards the construction of the string dual of a genuinely multi-scale (strongly coupled) dynamical model.Comment: 37 pages, 7 figures. References added, version to appear in JHE

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Quality of life in childhood epilepsy with lateralized epileptogenic foci

<p>Abstract</p> <p>Background</p> <p>Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges.</p> <p>Methods</p> <p>Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG) examinations.</p> <p>Results</p> <p>We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p < 0.046). Children with right hemispheric foci exhibited lower overall QOL, particularly in five areas: anxiety, social-activities, stigma, general-health, and quality-of-life.</p> <p>Conclusions</p> <p>We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development.</p

Characterization of CrN/CrAlN/Cr2O3 Multilayers Coatings Synthesized by DC Reactive Magnetron Sputtering

The CrN/CrAlN/Cr2O3 multilayer coatings were deposited by reactive magnetron sputtering DC on 90CrMoV8 stainless steel under various oxygen flow rates. The structure and crystalline phases are characterized by the x-ray diffractometer. Through SEM, a dense and coherent is revealed in CrN/CrAlN/Cr2O3 multilayer coatings. The friction and wear behaviors obtained with the ball-on-disc test show that all multilayer films exhibit a good wear resistance, especially the one with an oxygen flow rate of 10 sccm. Nevertheless, in sea water the film without a top layer of Cr2O3 have the lowest coefficient of friction. This behavior is attributed to the interfacial strengthening and the existence of the upper passivation layer Cr2O3. Adding to that, the film obtained under an oxygen flow rate of 10 sccm show the lowest grain size and the maximum hardness and elastic modulus could Respectively, 45 and 417 GPa.Région Bourgogn

Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease.

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.This work was funded by the Wellcome trust (103838), Parkinson’s UK, National Institute for Health Research’s Cambridge Biomedical Research Centre and the Medical Research Council (MC_US_A060_0016 and RG62761) and the James F McDonnell Foundation (21st century science initiative on Understanding Human Cognition). The BCNI is supported by a joint award from the Wellcome Trust and Medical Research Council.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2016.1