Narrowband UVB phototherapy for clinically isolated syndrome: A trial to deliver the benefits of Vitamin D and other UVB-Induced molecules

Low vitamin D and insufficient sun exposure are additive independent risk factors for the development of multiple sclerosis (MS). The usual measure of vitamin D status, serum 25-hydroxy vitamin D [25(OH)D], is also a marker of recent exposure to the UVB rays of sunshine. The main evidence for a protective effect for MS development of higher 25(OH)D comes from observational studies, but this study design cannot separate out whether 25(OH)D is acting as a marker of vitamin D status, sun exposure, or both. In light of a lack of definitive outcomes in MS patients after trials of vitamin D supplementation and the ability of narrowband UVB to induce vitamin D, as well as other immune-regulatory molecules in skin, the Phototherapy for Clinically Isolated Syndrome (PhoCIS) trial was established to investigate the benefits of narrowband UVB, in addition to supplemented vitamin D, on MS development in individuals with Clinically Isolated Syndrome. We propose that the PhoCIS trial provides a fresh approach to re-defining the reported associations of 25(OH)D levels with MS development and progression

Higher serum immunoglobulin G3 levels may predict the development of multiple sclerosis in individuals with Clinically Isolated Syndrome

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS

Association of TMTC2 with human nonsyndromic sensorineural hearing loss

IMPORTANCE: Sensorineural hearing loss (SNHL) is commonly caused by conditions that affect cochlear structures or the auditory nerve, and the genes identified as causing SNHL to date only explain a fraction of the overall genetic risk for this debilitating disorder. It is likely that other genes and mutations also cause SNHL. OBJECTIVE: To identify a candidate gene that causes bilateral, symmetric, progressive SNHL in a large multigeneration family of Northern European descent. DESIGN, SETTING, AND PARTICIPANTS: In this prospective genotype and phenotype study performed from January 1, 2006, through April 1, 2016, a 6-generation family of Northern European descent with 19 individuals having reported early-onset hearing loss suggestive of an autosomal dominant inheritance were studied at a tertiary academic medical center. In addition, 179 unrelated adult individuals with SNHL and 186 adult individuals reporting nondeafness were examined. MAIN OUTCOMES AND MEASURES: Sensorineural hearing loss. RESULTS: Nine family members (5 women [55.6%]) provided clinical audiometric and medical records that documented hearing loss. The hearing loss is characterized as bilateral, symmetric, progressive SNHL that reached severe to profound loss in childhood. Audiometric configurations demonstrated a characteristic dip at 1000 to 2000 Hz. All affected family members wear hearing aids or have undergone cochlear implantation. Exome sequencing and linkage and association analyses identified a fully penetrant sequence variant (rs35725509) on chromosome 12q21 (logarithm of odds, 3.3) in the TMTC2 gene region that segregates with SNHL in this family. This gene explains the SNHL occurrence in this family. The variant is also associated with SNHL in a cohort of 363 unrelated individuals (179 patients with confirmed SNHL and 184 controls, P = 7 x 10-4). CONCLUSIONS AND RELEVANCE: A previously uncharacterized gene, TMTC2, has been identified as a candidate for causing progressive SNHL in humans. This finding identifies a novel locus that causes autosomal dominant SNHL and therefore a more detailed understanding of the genetic basis of SNHL. Because TMTC2 has not been previously reported to regulate auditory function, the discovery reveals a potentially new, uncharacterized mechanism of hearing loss

The kk-essence scalar field in the context of Supernova Ia Observations

A $k$-essence scalar field model having (non canonical) Lagrangian of the form $L=-V(\phi)F(X)$ where $X=1/2g^{\mu\nu}\nabla_{\mu}\phi\nabla_{\nu}\phi$ with constant $V(\phi)$ is shown to be consistent with luminosity distance-redshift data observed for type Ia Supernova. For constant $V(\phi)$, $F(X)$ satisfies a scaling relation which is used to set up a differential equation involving the Hubble parameter $H$, the scale factor $a$ and the $k$-essence field $\phi$. $H$ and $a$ are extracted from SNe Ia data and using the differential equation the time dependence of the field $\phi$ is found to be: $\phi(t) \sim \lambda_0 + \lambda_1 t + \lambda_2 t^2$. The constants $\lambda_i$ have been determined. The time dependence is similar to that of the quintessence scalar field (having canonical kinetic energy) responsible for homogeneous inflation. Furthermore, the scaling relation and the obtained time dependence of the field $\phi$ is used to determine the $X$-dependence of the function $F(X)$.Comment: 8 pages, 5 figures, Late

A Systematic Literature Review of Emotion Regulation Measurement in Individuals With Autism Spectrum Disorder

DOI: 10.1002/aur.1426Emotion regulation (ER) difficulties are a potential common factor underlying the presentation of multiple emotional and behavioral problems in individuals with Autism Spectrum Disorder (ASD). To provide an overview of how ER has been studied in individuals with ASD, we conducted a systematic review of the past 20 years of ER research in the ASD population, using established keywords from the most comprehensive ER literature review of the typically developing population to date. Out of an initial sampling of 305 studies, 32 were eligible for review. We examined the types of methods (self-report, informant report, naturalistic observation/ behavior coding, physiological, and open-ended) and the ER constructs based on Gross and Thompson’s modal model (situation selection, situation modification, attention deployment, cognitive change, and response modulation). Studies most often assessed ER using one type of method and from a unidimensional perspective. Across the 32 studies, we documented the types of measures used and found that 38% of studies used self-report, 44% included an informant report measure, 31% included at least one naturalistic observation/behavior coding measure, 13% included at least one physiological measure, and 13% included at least one open-ended measure. Only 25% of studies used more than one method of measurement. The findings of the current review provide the field with an in-depth analysis of various ER measures and how each measure taps into an ER framework. Future research can use this model to examine ER in a multicomponent way and through multiple methods.Spectrum of Hope Autism Foundation, Canadian Institutes of Health Research, NeuroDevNet, Sinneave Family Foundation, CASDA, Autism Speaks Canada, Health Canad

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Λ\LambdaCDM, Λ\LambdaDGP and extended phantom-like cosmologies

In this paper we compare outcomes of some extended phantom-like cosmologies with each other and also with $\Lambda$CDM\, and $\Lambda$DGP. We focus on the variation of the luminosity distances, the age of the universe and the deceleration parameter versus the redshift in these scenarios. In a dynamical system approach, we show that the accelerating phase of the universe in the $f(R)$-DGP scenario is stable if one consider the \emph{curvature fluid} as a phantom scalar field in the equivalent scalar-tensor theory, otherwise it is a transient and unstable phenomenon. Up to the parameters values adopted in this paper, the extended $F(R,\phi)$-DGP scenario is closer to the $\Lambda$CDM scenario than other proposed models. All of these scenarios explain the late-time cosmic speed-up in their normal DGP branches, but the redshift at which transition to the accelerating phase occurs are different: while the $\Lambda$DGP model transits to the accelerating phase much earlier, the $F(R,\phi)$-DGP model transits to this phase much later than other scenarios. Also, within the parameter spaces adopted in this paper, the age of the universe in the $f(R)$-DGP model is larger than $\Lambda$CDM, but this age in $F(G,\phi)$-DGP is smaller than $\Lambda$CDM.Comment: 37 pages, 6 figures, accepted for publication in Astrophyics and Space Scienc