Genetic mouse models of migraine

Mouse models of rare monogenic forms of migraine provide a unique experimental system to study the cellular and circuit mechanisms of the primary brain dysfunctions causing a migraine disorder. Here, we discuss the migraine-relevant phenotypes and the migraine-relevant functional alterations in the brain of five genetic mouse models of migraine, four of which carry mutations derived from patients with familial hemiplegic migraine (FHM) and the fifth carry a mutation from patients with both phenotypically normal MA and familial advanced sleep phase syndrome (FASPS). We focus on the latter mouse model, in which a ubiquitous serine-threonine kinase is mutated, and on two mouse models of pure FHM, in which a voltage-gated calcium channel controlling neurotransmitter release at most brain synapses and a Na/K ATPase that is expressed mainly in astrocytes in the adult brain are mutated, respectively. First, we describe the behavioral phenotypes of the genetic animal models and review the evidence that an increased susceptibility to experimentally induced cortical spreading depression (CSD) is a key migraine-relevant phenotype common to the five models. Second, we review the synaptic alterations in the cerebral cortex of the genetic models of migraine and discuss the mechanisms underlying their increased susceptibility to CSD. Third, we review the alterations in the trigeminovascular pain pathway and discuss possible implications for migraine pain mechanisms. Finally, we discuss the insights into migraine pathophysiology obtained from the genetic models of migraine, in particular regarding the mechanisms that make the brain of migraineurs susceptible to the ignition of "spontaneous" CSDs. Although the reviewed functional studies support the view of migraine as a disorder of the brain characterized by dysfunctional regulation of the excitatory/inhibitory balance in specific neuronal circuits, much work remains to be done in the genetic mouse models e.g. to identfy the relevant dysfunctional circuits and to establish whether and how the alterations in the function of specific circuits (in the cerebral cortex and/or other brain areas) are state-dependent and may, in certain conditions, favor CSD ignition and the migraine attack

Searching for a dipole modulation in the large-scale structure of the Universe

Several statistical anomalies in the CMB temperature anisotropies seem to defy the assumption of a homogeneous and isotropic universe. In particular, a dipole modulation has been detected both in WMAP and Planck data. We adapt the methodology proposed by Eriksen et al. (2007) on CMB data to galaxy surveys, tracing the large-scale structure. We analyse the NRAO VLA Sky Survey (NVSS) data at a resolution of ~2 degrees for three different flux thresholds: 2.5, 5.0 and 10.0 mJy respectively. No evidence of a dipole modulation is found. This result suggests that the origin of the dipole asymmetry found in the CMB cannot be assigned to secondary anisotropies produced at redshifts around z = 1. However, it could still have been generated at redshifts higher or lower, such as the integrated Sachs-Wolfe effect produced by the local structures. Other all-sky surveys, like the infrared WISE catalogue, could help to explore with a high sensitivity a redshift interval closer than the one probed with NVSS.Comment: 6 pages, 2 figures. Some minor changes have been done from the original manuscript. This paper is accepted by MNRA

Spherical Needlets for CMB Data Analysis

We discuss Spherical Needlets and their properties. Needlets are a form of spherical wavelets which do not rely on any kind of tangent plane approximation and enjoy good localization properties in both pixel and harmonic space; moreover needlets coefficients are asymptotically uncorrelated at any fixed angular distance, which makes their use in statistical procedures very promising. In view of these properties, we believe needlets may turn out to be especially useful in the analysis of Cosmic Microwave Background (CMB) data on the incomplete sky, as well as of other cosmological observations. As a final advantage, we stress that the implementation of needlets is computationally very convenient and may rely completely on standard data analysis packages such as HEALPix.Comment: 7 pages, 7 figure

Foreground influence on primordial non-Gaussianity estimates: needlet analysis of WMAP 5-year data

We constrain the amplitude of primordial non-Gaussianity in the CMB data taking into account the presence of foreground residuals in the maps. We generalise the needlet bispectrum estimator marginalizing over the amplitudes of thermal dust, free-free and synchrotron templates. We apply our procedure to WMAP 5 year data, finding fNL= 38\pm 47 (1 \sigma), while the analysis without marginalization provides fNL= 35\pm 42. Splitting the marginalization over each foreground separately, we found that the estimates of fNL are positively cross correlated of 17%, 12% with the dust and synchrotron respectively, while a negative cross correlation of about -10% is found for the free-free component.Comment: Submitted to MNRA

Affine equation of state from quintessence and k-essence fields

We explore the possibility that a scalar field with appropriate Lagrangian can mimic a perfect fluid with an affine barotropic equation of state. The latter can be thought of as a generic cosmological dark component evolving as an effective cosmological constant plus a generalized dark matter. As such, it can be used as a simple, phenomenological model for either dark energy or unified dark matter. Furthermore, it can approximate (up to first order in the energy density) any barotropic dark fluid with arbitrary equation of state. We find that two kinds of Lagrangian for the scalar field can reproduce the desired behaviour: a quintessence-like with a hyperbolic potential, or a purely kinetic k-essence one. We discuss the behaviour of these two classes of models from the point of view of the cosmological background, and we give some hints on their possible clustering properties.Comment: 9 pages, 6 figures. Minor updates, accepted by CQ

Needlet Detection of Features in WMAP CMB Sky and the Impact on Anisotropies and Hemispherical Asymmetries

We apply spherical needlets to the Wilkinson Microwave Anisotropy Probe 5-year cosmic microwave background (CMB) dataset, to search for imprints of non-isotropic features in the CMB sky. We use the needlets localization properties to resolve peculiar features in the CMB sky and to study how these features contribute to the anisotropy power spectrum of the CMB. In addition to the now well-known "cold spot" of the CMB map in the southern hemisphere, we also find two hot spots at greater than 99% confidence level, again in the southern hemisphere and closer to the Galactic plane. While the cold spot contributes to the anisotropy power spectrum in the multipoles between l=6 to l=33, the hot spots are found to be dominating the anisotropy power in the range between l=6 and l=18. Masking both the cold and the two hot spots results in a reduction by about 15% in the amplitude of the angular power spectrum of CMB around l=10. The resulting changes to the cosmological parameters when the power spectrum is estimated masking these features (in addition to the WMAP team's KQ85 mask) are within the 1$\sigma$ errors published with the WMAP mask only. We also study the asymmetry between the angular power spectra evaluated on the northern and southern hemispheres. When the features detected by needlets are masked, we find that the difference in the power, measured in terms of the anisotropy variance between l=4 and l=18, is reduced by a factor 2. We make available a mask related to needlet features for more detailed studies on asymmetries in the CMB anisotropy sky.Comment: 12 pages, 12 figures; masks available at http://www.fisica.uniroma2.it/~cosmo/mask

Searching for planar signatures in WMAP

We search for planar deviations of statistical isotropy in the Wilkinson Microwave Anisotropy Probe (WMAP) data by applying a recently introduced angular-planar statistics both to full-sky and to masked temperature maps, including in our analysis the effect of the residual foreground contamination and systematics in the foreground removing process as sources of error. We confirm earlier findings that full-sky maps exhibit anomalies at the planar ($l$) and angular ($\ell$) scales $(l,\ell)=(2,5),(4,7),$ and $(6,8)$, which seem to be due to unremoved foregrounds since this features are present in the full-sky map but not in the masked maps. On the other hand, our test detects slightly anomalous results at the scales $(l,\ell)=(10,8)$ and $(2,9)$ in the masked maps but not in the full-sky one, indicating that the foreground cleaning procedure (used to generate the full-sky map) could not only be creating false anomalies but also hiding existing ones. We also find a significant trace of an anomaly in the full-sky map at the scale $(l,\ell)=(10,5)$, which is still present when we consider galactic cuts of 18.3% and 28.4%. As regards the quadrupole ($\ell=2$), we find a coherent over-modulation over the whole celestial sphere, for all full-sky and cut-sky maps. Overall, our results seem to indicate that current CMB maps derived from WMAP data do not show significant signs of anisotropies, as measured by our angular-planar estimator. However, we have detected a curious coherence of planar modulations at angular scales of the order of the galaxy's plane, which may be an indication of residual contaminations in the full- and cut-sky maps.Comment: 15 pages with pdf figure

Addressing disparities in European cancer outcomes: a qualitative study Protocol of the BEACON project

Introduction: Health disparities represent a crucial factor in cancer survival rates, awareness, quality of life, and mental health of people receiving a cancer diagnosis and their families. Income, education, geographic location, and ethnicity are some of the most important underlying reasons for health disparities in cancer across Europe. Costs of healthcare, access to information, psycho-oncological support options, integration of cancer research and innovative care, and multidisciplinary cancer teams are the main target areas when it comes to addressing disparities in the cancer context. As part of the Beacon Project (BEACON), we developed a protocol for a qualitative study to explore and identify any relevant reasons for cancer inequalities and disparities in Europe. Methods: Our four stakeholders namely, cancer patients, healthcare providers, researchers, and policymakers will be recruited online, facilitated by collaborative efforts with cancer organizations from various European countries, including but not limited to Italy, Croatia, Estonia, and Slovenia. Qualitative online focus group discussions for each stakeholder will be conducted and transcribed. Subsequently, thematic analysis will be used to identify reasons and aspects that may contribute to the existing disparities in cancer outcomes at various levels of engagement and from different stakeholders’ perspectives. Results from focus groups will inform a subsequent Delphi study and a SWOT analysis methodology. Discussion: Although advances in medical research, cancer screening and treatment options are constantly progressing, disparities in access to and awareness of healthcare in cancer patients are even more noticeable. Thus, mapping the capacity and capability of cancer centres in the European Union, creating decision support tools that will assist the four stakeholders’ information needs and improving the quality of European cancer centres will be the main objectives of the BEACON project. The current protocol will outline the methodological and practical procedures to conduct online focus group discussions with different stakeholders

Predicting gender differences as latent variables: summed scores, and individual item responses: a methods case study

BACKGROUND: Modeling latent variables such as physical disability is challenging since its measurement is performed through proxies. This poses significant methodological challenges. The objective of this article is to present three different methods to predict latent variables based on classical summed scores, individual item responses, and latent variable models. METHODS: This is a review of the literature and data analysis using "layers of information". Data was collected from the North Carolina Back Pain Project, using a modified version of the Roland Questionnaire. RESULTS: The three models are compared in relation to their goals and underlying concepts, previous clinical applications, data requirements, statistical theory, and practical applications. Initial linear regression models demonstrated a difference in disability between genders of 1.32 points (95% CI 0.65, 2.00) on a scale from 0–23. Subsequent item analysis found contradictory results across items, with no clear pattern. Finally, IRT models demonstrated three items were demonstrated to present differential item functioning. After these items were removed, the difference between genders was reduced to 0.78 points (95% CI, -0.99, 1.23). These results were shown to be robust with re-sampling methods. CONCLUSIONS: Purported differences in the levels of a latent variable should be tested using different models to verify whether these differences are real or simply distorted by model assumptions