Large-scale Roll Out of Electronic Longitudinal Mood-Monitoring for Research in Affective Disorders: Report From the UK Bipolar Disorder Research Network

Background Electronic longitudinal mood monitoring has been shown to be acceptable to patients with affective disorders within clinical settings, but its use in large-scale research has not yet been established. Methods Using both postal and email invitations, we invited 4080 past research participants with affective disorders who were recruited into the Bipolar Disorder Research Network (BDRN) over a 10 year period to participate in online weekly mood monitoring. In addition, since January 2015 we have invited all newly recruited BDRN research participants to participate in mood monitoring at the point they were recruited into BDRN. Results Online mood monitoring uptake among past participants was 20, and among new participants to date was 46 with participants recruited over the last year most likely to register (61). More than 90 mood monitoring participants engaged for at least one month, with mean engagement period greater than one year (58 weeks) and maximum engagement for longer than three years (165 weeks). There were no significant differences in the proportion of past and new BDRN participants providing data for at least 4 weeks (91, 92 respectively), 3 months (78, 82), 6 months (65, 54) or one year (51, 44). Limitations Our experiences with recruiting participants for electronic prospective mood monitoring may not necessarily generalise fully to research situations that are very different from those we describe. Conclusions Large-scale electronic longitudinal mood monitoring in affective disorders for research purposes is feasible with uptake highest among newly recruited participants

The Collapse of Large Extra Dimensions

In models of spacetime that are the product of a four-dimensional spacetime with an ``extra'' dimension, there is the possibility that the extra dimension will collapse to zero size, forming a singularity. We ask whether this collapse is likely to destroy the spacetime. We argue, by an appeal to the four-dimensional cosmic censorship conjecture, that--at least in the case when the extra dimension is homogeneous--such a collapse will lead to a singularity hidden within a black string. We also construct explicit initial data for a spacetime in which such a collapse is guaranteed to occur and show how the formation of a naked singularity is likely avoided.Comment: Uses revtex

Development and internal validation of a prediction tool to aid the diagnosis of Cushing's syndrome in dogs attending primary-care practice.

Novel methods to aid identification of dogs with spontaneous Cushing's syndrome are warranted to optimize case selection for diagnostics, avoid unnecessary testing, and ultimately aid decision-making for veterinarians. To develop and internally validate a prediction tool for dogs receiving a diagnosis of Cushing's syndrome using primary-care electronic health records. Three hundred and ninety-eight dogs diagnosed with Cushing's syndrome and 541 noncase dogs, tested for but not diagnosed with Cushing's syndrome, from a cohort of 905 544 dogs attending VetCompass participating practices. A cross-sectional study design was performed. A prediction model was developed using multivariable binary logistic regression taking the demography, presenting clinical signs and some routine laboratory results into consideration. Predictive performance of each model was assessed and internally validated through bootstrap resampling. A novel clinical prediction tool was developed from the final model. The final model included predictor variables sex, age, breed, polydipsia, vomiting, potbelly/hepatomegaly, alopecia, pruritus, alkaline phosphatase, and urine specific gravity. The model demonstrated good discrimination (area under the receiver operating curve [AUROC] = 0.78 [95% CI = 0.75-0.81]; optimism-adjusted AUROC = 0.76) and calibration (C-slope = 0.86). A tool was developed from the model which calculates the predicted likelihood of a dog having Cushing's syndrome from 0% (score = -13) to 96% (score = 10). A tool to predict a diagnosis of Cushing's syndrome at the point of first suspicion in dogs was developed, with good predictive performance. This tool can be used in practice to support decision-making and increase confidence in diagnosis. [Abstract copyright: © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.

Classical Stabilization of Homogeneous Extra Dimensions

If spacetime possesses extra dimensions of size and curvature radii much larger than the Planck or string scales, the dynamics of these extra dimensions should be governed by classical general relativity. We argue that in general relativity, it is highly nontrivial to obtain solutions where the extra dimensions are static and are dynamically stable to small perturbations. We also illustrate that intuition on equilibrium and stability built up from non-gravitational physics can be highly misleading. For all static, homogeneous solutions satisfying the null energy condition, we show that the Ricci curvature of space must be nonnegative in all directions. Much of our analysis focuses on a class of spacetime models where space consists of a product of homogeneous and isotropic geometries. A dimensional reduction of these models is performed, and their stability to perturbations that preserve the spatial symmetries is analyzed. We conclude that the only physically realistic examples of classically stabilized large extra dimensions are those in which the extra-dimensional manifold is positively curved.Comment: 25 pages; minor changes, improved reference

History of Premenstrual Mood Change and Postpartum Episodes are Associated with Perimenopausal Episodes in Women with Bipolar Disorder

Background and Aims: Reproductive life events are potential triggers of mood episodes in women with bipolar disorder. We aimed to establish whether a history of premenstrual mood change and postpartum episodes are associated with perimenopausal episodes in women who have bipolar disorder. Methods: Participants were 339 post-menopausal women with DSM-IV bipolar disorder recruited into the Bipolar Disorder Research Network (www.bdrn.org). Women self-reported presence (N = 200) or absence (N = 139) of an illness episode during the perimenopausal period. History of premenstrual mood change was measured using the self-report Premenstrual Symptoms Screening Tool (PSST), and history of postpartum episodes was measured via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry, SCAN) and inspection of case-notes. Results: History of a postpartum episode within 6 months of delivery (OR = 2.13, p = 0.03) and history of moderate/severe premenstrual syndrome (OR = 6.33, p < 0.001) were significant predictors of the presence of a perimenopausal episode, even after controlling for demographic factors. When we narrowed the definition of premenstrual mood change to premenstrual dysphoric disorder, it remained significant (OR = 2.68, p = 0.007). Conclusions: Some women who have bipolar disorder may be particularly sensitive to reproductive life events. Previous mood episodes in relation to the female reproductive lifecycle may help clinicians predict individual risk for women with bipolar disorder approaching the menopause. There is a need for prospective longitudinal studies of women with bipolar disorder providing frequent contemporaneous ratings of their mood to overcome the limitations of retrospective self-report data

Collisional kinetics of non-uniform electric field, low-pressure, direct-current discharges in H2_{2}

A model of the collisional kinetics of energetic hydrogen atoms, molecules, and ions in pure H$_2$ discharges is used to predict H$_\alpha$ emission profiles and spatial distributions of emission from the cathode regions of low-pressure, weakly-ionized discharges for comparison with a wide variety of experiments. Positive and negative ion energy distributions are also predicted. The model developed for spatially uniform electric fields and current densities less than $10^{-3}$ A/m$^2$ is extended to non-uniform electric fields, current densities of $10^{3}$ A/m$^2$, and electric field to gas density ratios $E/N = 1.3$ MTd at 0.002 to 5 Torr pressure. (1 Td = $10^{-21}$ V m$^2$ and 1 Torr = 133 Pa) The observed far-wing Doppler broadening and spatial distribution of the H$_\alpha$ emission is consistent with reactions among H$^+$, H$_2^+$, H$_3^+$, and H$^-H$ ions, fast H atoms, and fast H$_2$ molecules, and with reflection, excitation, and attachment to fast H atoms at surfaces. The H$_\alpha$ excitation and H$^-$ formation occur principally by collisions of fast H, fast H$_2$, and H$^+$ with H$_2$. Simplifications include using a one-dimensional geometry, a multi-beam transport model, and the average cathode-fall electric field. The H$_\alpha$ emission is linear with current density over eight orders of magnitude. The calculated ion energy distributions agree satisfactorily with experiment for H$_2^+$ and H$_3^+$, but are only in qualitative agreement for H$^+$ and H$^-$. The experiments successfully modeled range from short-gap, parallel-plane glow discharges to beam-like, electrostatic-confinement discharges.Comment: Submitted to Plasmas Sources Science and Technology 8/18/201

Multidimensional cosmological models: cosmological and astrophysical implications and constraints

We investigate four-dimensional effective theories which are obtained by dimensional reduction of multidimensional cosmological models with factorizable geometry and consider the interaction between conformal excitations of the internal space (geometrical moduli excitations) and Abelian gauge fields. It is assumed that the internal space background can be stabilized by minima of an effective potential. The conformal excitations over such a background have the form of massive scalar fields (gravitational excitons) propagating in the external spacetime. We discuss cosmological and astrophysical implications of the interaction between gravexcitons and four-dimensional photons as well as constraints arising on multidimensional models of the type considered in our paper. In particular, we show that due to the experimental bounds on the variation of the fine structure constant, gravexcitons should decay before nucleosynthesis starts. For a successful nucleosynthesis the masses of the decaying gravexcitons should be m>10^4 GeV. Furthermore, we discuss the possible contribution of gravexcitons to UHECR. It is shown that, at energies of about 10^{20}eV, the decay length of gravexcitons with masses m>10^4 GeV is very small, but that for m <10^2 GeV it becomes much larger than the Greisen-Zatsepin-Kuzmin cut-off distance. Finally, we investigate the possibility for gravexciton-photon oscillations in strong magnetic fields of astrophysical objects. The corresponding estimates indicate that even the high magnetic field strengths of magnetars are not sufficient for an efficient and copious production of gravexcitons.Comment: 16 pages, LaTeX2e, minor changes, improved references, to appear in PR

Nonlinear multidimensional cosmological models with form fields: stabilization of extra dimensions and the cosmological constant problem

We consider multidimensional gravitational models with a nonlinear scalar curvature term and form fields in the action functional. In our scenario it is assumed that the higher dimensional spacetime undergoes a spontaneous compactification to a warped product manifold. Particular attention is paid to models with quadratic scalar curvature terms and a Freund-Rubin-like ansatz for solitonic form fields. It is shown that for certain parameter ranges the extra dimensions are stabilized. In particular, stabilization is possible for any sign of the internal space curvature, the bulk cosmological constant and of the effective four-dimensional cosmological constant. Moreover, the effective cosmological constant can satisfy the observable limit on the dark energy density. Finally, we discuss the restrictions on the parameters of the considered nonlinear models and how they follow from the connection between the D-dimensional and the four-dimensional fundamental mass scales.Comment: 21 pages, LaTeX2e, minor changes, improved references, fonts include

User perspectives on long-term remote active electronic self-monitoring of mood symptoms in bipolar spectrum disorders

Background User feedback is crucial in the development of electronic self-monitoring tools for bipolar spectrum disorders (BSD). Previous studies have examined user experiences in small samples self-monitoring over relatively short time periods. We aimed to explore the experiences of a large sample of individuals with BSD engaged in long-term remote active electronic self-monitoring. Methods An online survey, containing closed and open questions, was sent to participants with BSD enrolled on the Bipolar Disorder Research Network (BDRN) True Colours mood-monitoring system. Questions related to experiences of using True Colours, including viewing mood graphs, and sharing data with healthcare professionals (HCPs) and/or family/friends. Results Response rate was 62.7 % (n = 362). 88.4 % reported finding using True Colours helpful. Commonly reported benefits were having a visual record of mood changes, patterns/triggers and identifying early warning signs. Limitations included questions not being comprehensive or revealing anything new. One third had shared their graphs, with 89.9 % finding it helpful to share with HCPs and 78.7 % helpful to share with family/friends. Perceived benefits included aiding communication and limitations included lack of interest/understanding from others. Limitations Responder bias may be present. Findings may not be generalisable to all research cohorts. Conclusions The majority of participants valued long-term self-monitoring. Personalisation and ease of use were important. A potential challenge is continued use when mood is long-term stable, highlighting the need for measures to be sensitive to small changes. Sharing self-monitoring data with HCPs may enhance communication of the lived experience of those with BSD. Future research should examine HCPs' perspectives

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

Acknowledgements We wish to thank Jorge Galán, Gregory Pazour, Derek Toomre, Giuliano Callaini, Joel Rosenbaum, Alessandra Boletta and Francesco Blasi for generously providing reagents and for productive discussions, and Sonia Grassini for technical assistance. The work was carried out with the financial support of Telethon (GGP11021) and AIRC.Peer reviewedPostprin