Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study

Observational evidence has implicated vitamin D levels as a risk factor in major depressive disorder (MDD). Confounding or reverse causation may be driving these observed associations, with studies using genetics indicating little evidence of an effect. However, genetic studies have relied on broad definitions of depression. The genetic architecture of different depression subtypes may vary since MDD is a highly heterogenous condition, implying potentially diverging requirements in therapeutic approaches. We explored the associations between vitamin D and two subtypes of MDD, for which evidence of a causal link could have the greatest clinical benefits: treatment-resistant depression (TRD) and atypical depression (AD). We used a dual approach, combining observational data with genetic evidence from polygenic risk scores (PRS) and two-sample Mendelian randomization (MR), in the UK Biobank. There was some evidence of a weak association between vitamin D and both incident TRD (Ncases = 830) and AD (Ncases = 2366) in observational analyses, which largely attenuated when adjusting for confounders. Genetic evidence from PRS and two-sample MR, did not support a causal link between vitamin D and either TRD (Ncases = 1891, OR = 1.01 [95%CI 0.78, 1.31]) or AD (Ncases = 2101, OR = 1.04 [95%CI 0.80, 1.36]). Our comprehensive investigations indicated some evidence of an association between vitamin D and TRD/AD observationally, but little evidence of association when using PRS and MR, mirroring findings of genetic studies of vitamin D on broad depression phenotypes. Results do not support further clinical trials of vitamin D in these MDD subtypes but do not rule out that small effects may exist that require larger samples to detect

The time to extinction for an SIS-household-epidemic model

We analyse a stochastic SIS epidemic amongst a finite population partitioned into households. Since the population is finite, the epidemic will eventually go extinct, i.e., have no more infectives in the population. We study the effects of population size and within household transmission upon the time to extinction. This is done through two approximations. The first approximation is suitable for all levels of within household transmission and is based upon an Ornstein-Uhlenbeck process approximation for the diseases fluctuations about an endemic level relying on a large population. The second approximation is suitable for high levels of within household transmission and approximates the number of infectious households by a simple homogeneously mixing SIS model with the households replaced by individuals. The analysis, supported by a simulation study, shows that the mean time to extinction is minimized by moderate levels of within household transmission

Preparative fractionation of a random copolymer (SAN) with respect to either chain length or chemical composition

The possibilities to fractionate copolymers with respect to their chemical composition on a preparative scale by means of the establishment of liquid/liquid phase equilibria were studied for random copolymers of styrene and acrylonitrile (san). Experiments with solutions of san in toluene have shown that fractionation does in this quasi-binary system, where demixing results from marginal solvent quality, take place with respect to the chain length of the polymer only. On the other hand, if phase separation is induced by a second, chemically different polymer one can find conditions under which fractionation with respect to composition becomes dominant. This opportunity is documented for the quasi-ternary system dmac/san/polystyrene, where the solvent dimethyl acetamide is completely miscible with both polymers. The theoretical reasons for the different fractionation mechanisms are discussed

Numerical studies of the phase diagram of layered type II superconductors in a magnetic field

We report on simulations of layered superconductors using the Lawrence-Doniach model in the framework of the lowest Landau level approximation. We find a first order phase transition with a $B(T)$ dependence which agrees very well with the experimental ``melting'' line in YBaCuO. The transition is not associated with vortex lattice melting, but separates two vortex liquid states characterised by different degrees of short-range crystalline order and different length scales of correlations between vortices in different layers. The transition line ends at a critical end-point at low fields. We find the magnetization discontinuity and the location of the lower critical magnetic field to be in good agreement with experiments in YBaCuO. Length scales of order parameter correlations parallel and perpendicular to the magnetic field increase exponentially as 1/T at low temperatures. The dominant relaxation time scales grow roughly exponentially with these correlation lengths. We find that the first order phase transition persists in the presence of weak random point disorder but can be suppressed entirely by strong disorder. No vortex glass or Bragg glass state is found in the presence of disorder. The consistency of our numerical results with various experimental features in YBaCuO, including the dependence on anisotropy, and the temperature dependence of the structure factor at the Bragg peaks in neutron scattering experiments is demonstrated.Comment: 25 pages (revtex), 19 figures included, submitted to PR

Transverse depinning and melting of a moving vortex lattice in driven periodic Josephson junction arrays

We study the effect of thermal fluctuations in a vortex lattice driven in the periodic pinning of a Josephson junction array. The phase diagram current ($I$) vs. temperature ($T$) is studied. Above the critical current $I_c(T)$ we find a moving vortex lattice (MVL) with anisotropic Bragg peaks. For large currents $I\gg I_c(T)$, there is a melting transition of the MVL at $T_M(I)$. When applying a small transverse current to the MVL, there is no dissipation at low $T$. We find an onset of transverse vortex motion at a transverse depinning temperature $T_{tr}(I)<T_M(I)$.Comment: 4 pages, 4 figures, Figure 2 changed, added new reference

Genetic variants linked to education predict longevity

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total ndeaths= 79,702) and ∼2.4% lower risk for fathers (total ndeaths= 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity

Superconducting Coherence and the Helicity Modulus in Vortex Line Models

We show how commonly used models for vortex lines in three dimensional superconductors can be modified to include k=0 excitations. We construct a formula for the k=0 helicity modulus in terms of fluctuations in the projected area of vortex loops. This gives a convenient criterion for the presence of superconducting coherence. We also present Monte Carlo simulations of a continuum vortex line model for the melting of the Abrikosov vortex lattice in pure YBCO.Comment: 4 pages RevTeX, 2 eps figures included using eps

Effects of Electronic Correlations on the Thermoelectric Power of the Cuprates

We show that important anomalous features of the normal-state thermoelectric power S of high-Tc materials can be understood as being caused by doping dependent short-range antiferromagnetic correlations. The theory is based on the fluctuation-exchange approximation applied to Hubbard model in the framework of the Kubo formalism. Firstly, the characteristic maximum of S as function of temperature can be explained by the anomalous momentum dependence of the single-particle scattering rate. Secondly, we discuss the role of the actual Fermi surface shape for the occurrence of a sign change of S as a function of temperature and doping.Comment: 4 pages, with eps figure

Melting and transverse depinning of driven vortex lattices in the periodic pinning of Josephson junction arrays

We study the non-equilibrium dynamical regimes of a moving vortex lattice in the periodic pinning of a Josephson junction array (JJA) for {\it finite temperatures} in the case of a fractional or submatching field. We obtain a phase diagram for the current driven JJA as a function of the driving current I and temperature T. We find that when the vortex lattice is driven by a current, the depinning transition at $T_p(I)$ and the melting transition at $T_M(I)$ become separated even for a field for which they coincide in equilibrium. We also distinguish between the depinning of the vortex lattice in the direction of the current drive, and the {\it transverse depinning} in the direction perpendicular to the drive. The transverse depinning corresponds to the onset of transverse resistance in a moving vortex lattice at a given temperature $T_{tr}$. For driving currents above the critical current we find that the moving vortex lattice has first a transverse depinning transition at low T, and later a melting transition at a higher temperature, $T_{M}>T_{tr}$.Comment: 17 pages, 19 figure

How can latent trajectories of back pain be translated into defined subgroups?

Background: Similar types of trajectory patterns have been identified by Latent Class Analyses (LCA) across multiple low back pain (LBP) cohorts, but these patterns are impractical to apply to new cohorts or individual patients. It would be useful to be able to identify trajectory subgroups from descriptive definitions, as a way to apply the same definitions of mutually exclusive subgroups across populations. In this study, we investigated if the course trajectories of two LBP cohorts fitted with previously suggested trajectory subgroup definitions, how distinctly different these subgroups were, and if the subgroup definitions matched with LCA-derived patterns. Methods: Weekly measures of LBP intensity and frequency during 1 year were available from two clinical cohorts. We applied definitions of 16 possible trajectory subgroups to these observations and calculated the prevalence of the subgroups. The probability of belonging to each of eight LCA-derived patterns was determined within each subgroup. LBP intensity and frequency were described within subgroups and the subgroups of 'fluctuating' and 'episodic' LBP were compared on clinical characteristics. Results: All of 1077 observed trajectories fitted with the defined subgroups. 'Severe episodic LBP' was the most frequent pattern in both cohorts and 'ongoing LBP' was almost non-existing. There was a clear relationship between the defined trajectory subgroups and LCA-derived trajectory patterns, as in most subgroups, all patients had high probabilities of belonging to only one or two of the LCA patterns. The characteristics of the six defined subgroups with minor LBP were very similar. 'Fluctuating LBP' subgroups were significantly more distressed, had more intense leg pain, higher levels of activity limitation, and more negative expectations about future LBP than 'episodic LBP' subgroups. Conclusion: Previously suggested definitions of LBP trajectory subgroups could be readily applied to patients' observed data resulting in subgroups that matched well with LCA-derived trajectory patterns. We suggest that the number of trajectory subgroups can be reduced by merging some subgroups with minor LBP. Stable levels of LBP were almost not observed and we suggest that minor fluctuations in pain intensity might be conceptualised as 'ongoing LBP'. Lastly, we found clear support for distinguishing between fluctuating and episodic LBP