A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder

Background: Melanopsin, a non-visual photopigment, may play a role in aberrant responses to low winter light levels in Seasonal Affective Disorder (SAD). We hypothesize that functional sequence variation in the melanopsin gene could contribute to increasing the light needed for normal functioning during winter in SAD. Methods: Associations between alleles, genotypes, and haplotypes of melanopsin in SAD participants (n = 130) were performed relative to controls with no history of psychopathology (n = 90). Results: SAD participants had a higher frequency of the homozygous minor genotype (T/T) for the missense variant rs2675703 (P10L) than controls, compared to the combined frequencies of C/C and C/T. Individuals with the T/T genotype were 5.6 times more likely to be in the SAD group than the control group, and all 7 (5%) of individuals with the T/T genotype at P10L were in the SAD group. Limitations: The study examined only one molecular component of the non-visual light input pathway, and recruitment methods for the comparison groups differed. Conclusion: These findings support the hypothesis that melanopsin variants may predispose some individuals to SAD. Characterizing the genetic basis for deficits in the non-visual light input pathway has the potential to define mechanisms underlying the pathological response to light in SAD, which may improve treatment. © 2008 Elsevier B.V

Metastable Vacua in Superconformal SQCD-like Theories

We study dynamical supersymmetry breaking in vector-like superconformal N=1 gauge theories. We find appropriate deformations of the superpotential to overcome the problem of the instability of the non supersymmetric vacuum. The request for long lifetime translates into constraints on the physical couplings which in this regime can be controlled through efficient RG analysis.Comment: 17 pages, 7 figures, JHEP3.cl

Non Supersymmetric Metastable Vacua in N=2 SYM Softly Broken to N=1

We find non-supersymmetric metastable vacua in four dimensional N=2 gauge theories softly broken to N=1 by a superpotential term. First we study the simplest case, namely the SU(2) gauge theory without flavors. We study the spectrum and lifetime of the metastable vacuum and possible embeddings of the model in UV complete theories. Then we consider larger gauge group theories with flavors. We show that when we softly break them to N=1, the potential induced on specific submanifolds of their moduli space is identical to the potential in lower rank gauge theories. Then we show that the potential increases when we move away from this submanifold, allowing us to construct metastable vacua on them in the theories that can be reduced to the SU(2) case.Comment: 29 pages, 10 figure

Direct Mediation and Metastable Supersymmetry Breaking for SO(10)

We examine a metastable $\mathcal{N}=1$ Macroscopic SO(N) SQCD model of Intriligator, Seiberg and Shih (ISS). We introduce various baryon and meson deformations, including multitrace operators and explore embedding an SO(10) parent of the standard model into two weakly gauged flavour sectors. Direct fundamental messengers and the symmetric pseudo-modulus messenger mediate SUSY breaking to the MSSM. Gaugino and sfermion masses are computed and compared for each deformation type. We also explore reducing the rank of the magnetic quark matrix of the ISS model and find an additional fundamental messenger.Comment: 43 pages, Latex. Version to appear in JHEP

Tree Level Metastability and Gauge Mediation in Baryon Deformed SQCD

We investigate supersymmetric QCD with gauge group SU(2) and a baryon deformation to the superpotential. The existence of an uplifted vacuum at the origin with tree level metastability is demonstrated. When this model is implemented in a direct gauge mediation scenario we therefore find gaugino masses which are comparable to sfermion masses and parameterised by an effective number of messengers 1/8. All deformations are well motivated by appealing to the electric theory and an R-symmetry. This R-symmetry is explicitly broken by the same term responsible for supersymmetry breaking. Moreover, the model does not suffer from the Landau pole problem and we find that it can be described in terms of just two scales: the weak scale and a high scale like the Planck or GUT scale. The model can be tested by searching for new particles at the TeV scale charged under the visible sector gauge group.Comment: 17 pages, 7 figures, updated reference

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Adverse drug reactions and off-label and unlicensed medicines in children: a nested case control study of inpatients in a pediatric hospital

Off-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs

A new framework to assess relative ecosystem vulnerability to climate change

Climate change poses a growing risk to global biodiversity. To prioritize conservation efforts, identification of the species and ecosystems most at risk from further changes in climatic conditions is critically needed. Although frameworks are available to assess species vulnerability to climate change, we still lack an easily implementable, ecosystem‐level perspective to inform landscape management. Here, we introduce a novel, spatially explicit vulnerability framework able to generate assessments at the ecosystem scale and apply it to Mozambican forest mangroves, which are under growing pressures from climate change. Results show that most of these ecosystems are currently highly vulnerable to sea level rise, while mangroves in the Zambezia and Nampula districts are highly vulnerable to both sea level rise and tropical storms. Altogether, we believe the introduced assessment framework has clear potential to inform conservation planning and management at various spatial scales, and help achieve adaptive management in the face of climatic uncertainties

Thermal Evolution of the Non Supersymmetric Metastable Vacua in N=2 SU(2) SYM Softly Broken to N=1

It has been shown that four dimensional N=2 gauge theories, softly broken to N=1 by a superpotential term, can accommodate metastable non-supersymmetric vacua in their moduli space. We study the SU(2) theory at high temperatures in order to determine whether a cooling universe settles in the metastable vacuum at zero temperature. We show that the corrections to the free energy because of the BPS dyons are such that may destroy the existence of the metastable vacuum at high temperatures. Nevertheless we demonstrate the universe can settle in the metastable vacuum, provided that the following two conditions are hold: first the superpotential term is not arbitrarily small in comparison to the strong coupling scale of the gauge theory, and second the metastable vacuum lies in the strongly coupled region of the moduli space.Comment: 32 pages, 30 figure