The effect of common genetic variation in 11β-hydroxysteroid dehydrogenase type 1 on hypothalamic-pituitary-adrenal axis activity and incident depression

Background: Accumulating evidence suggests that hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA axis) is involved in depression. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inert cortisone to active cortisol and is implicated in HPA axis regulation in animal studies. The aim of our study was to identify polymorphisms in 11β-HSD1 gene (HSD11B1) with consistent associations with increased HPA axis activity and relate those polymorphisms to depression. Methods: Twelve single-nucleotide polymorphisms (SNPs), including 11 tagging SNPs, were selected using the HapMap database and genotyped in 4228 participants of the population-based Rotterdam Study. The outcome measures were salivary cortisol levels after awakening, 30 min later, at 1700 h, at bedtime, and plasma levels of androstenedione (in women only). SNPs that were significantly associated with cortisol as well as androstenedione levels were also related to incident depression. Results: rs11119328 was associated with higher cortisol saliva samples collected at bedtime as well as higher androstenedione levels (P value after correction for multiple testing: 0.01 and 0.04, respectively). Carriers of this polymorphism had an increased risk of an incident depression (hazard ratio 1.28, 95% confidence interval 1.03-1.59). Two other SNPs, which were in high linkage disequilibrium with rs11119328, were related to higher cortisol levels but not with androstenedione levels. Conclusions: We identified one SNP, which was associated with increased salivary cortisol levels at nadir as well as higher androstenedione levels. Moreover, this SNP was also associated with a higher risk of an incident depression. This suggests that 11β-HSD1 is implicated in human HPA axis regulation and susceptibility to depression. Copyrigh

Free field realization of superstring theory on AdS3

The Coulomb gas representation of expectation values in SU(2) conformal field theory developed by Dotsenko is extended to the SL(2,R) WZW model and applied to bosonic string theory on AdS3 and to Type II superstrings on AdS3 x N. The spectral flow symmetry is included in the free field realization of vertex operators creating superstring states of both Ramond and Neveu-Schwarz sectors. Conjugate representations for these operators are constructed and a background charge prescription is designed to compute correlation functions. Two and three point functions of bosonic and fermionic string states in arbitrary winding sectors are calculated. Scattering amplitudes that violate winding number conservation are also discussed.Comment: 40 pages, typos corrected, references added, minor changes in presentation and details completed in the calculation of the R sector 2-point function. Version to appear in JHE

Giant Magnons under NS-NS and Melvin Fields

The giant magnon is a rotating spiky string configuration which has the same dispersion relation between the energy and angular momentum as that of a spin magnon. In this paper we investigate the effects of the NS-NS and Melvin fields on the giant magnon. We first analyze the energy and angular momenta of the two-spin spiky D-string moving on the $AdS_3\times S^1$ with the NS-NS field. Due to the infinite boundary of the AdS spacetime the D-string solution will extend to infinity and it appears the divergences. After adding the counter terms we obtain the dispersion relation of the corresponding giant magnon. The result shows that there will appear a prefactor before the angular momentum, in addition to some corrections in the sine function. We also see that the spiky profile of a rotating D-string plays an important role in mapping it to a spin magnon. We next investigate the energy and angular momentum of the one-spin spiky fundamental string moving on the $R \times S^2$ with the electric or magnetic Melvin field. The dispersion relation of the corresponding deformed giant magnon is also obtained. We discuss some properties of the correction terms and their relations to the spin chain with deformations.Comment: Latex 20 pages, mention D-string and add reference

Stirring Strongly Coupled Plasma

We determine the energy it takes to move a test quark along a circle of radius L with angular frequency w through the strongly coupled plasma of N=4 supersymmetric Yang-Mills (SYM) theory. We find that for most values of L and w the energy deposited by stirring the plasma in this way is governed either by the drag force acting on a test quark moving through the plasma in a straight line with speed v=Lw or by the energy radiated by a quark in circular motion in the absence of any plasma, whichever is larger. There is a continuous crossover from the drag-dominated regime to the radiation-dominated regime. In the crossover regime we find evidence for significant destructive interference between energy loss due to drag and that due to radiation as if in vacuum. The rotating quark thus serves as a model system in which the relative strength of, and interplay between, two different mechanisms of parton energy loss is accessible via a controlled classical gravity calculation. We close by speculating on the implications of our results for a quark that is moving through the plasma in a straight line while decelerating, although in this case the classical calculation breaks down at the same value of the deceleration at which the radiation-dominated regime sets in.Comment: 27 pages LaTex, 5 figure

Shockwaves and deep inelastic scattering within the gauge/gravity duality

Within the gauge/gravity correspondence, we discuss the general formulation of the shockwave metric which is dual to a 'nucleus' described by the strongly-coupled N=4 SYM theory in the limit where the number of colors Nc is arbitrarily large. We emphasize that the 'nucleus' must possess Nc^2 degrees of freedom per unit volume, so like a finite-temperature plasma, in order for a supergravity description to exist. We critically reassess previous proposals for introducing transverse inhomogeneity in the shockwave and formulate a new proposal in that sense, which involves no external source but requires the introduction of an 'infrared' cutoff which mimics confinement. This cutoff however plays no role when the shockwave is probed by a highly virtual projectile, so like in deep inelastic scattering. We consider two such projectiles, the dilaton and the R-current, and compute the respective structure functions including unitarity corrections. We find that there are no leading-twist contributions to the structure functions at high virtuality, meaning that there are no point-like constituents in the strongly coupled 'nucleus'. In the black-disk regime at low virtuality, the structure functions are suggestive of parton saturation with occupation numbers of order one. The saturation momentum Qs grows with the energy like Qs^2 ~ 1/x (with x the Bjorken variable), which is the hallmark of graviton exchanges and is also necessary for the fulfillment of the energy-momentum sum rules.Comment: 43 page

Heritability of the shape of subcortical brain structures in the general population

The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures

Jet evolution in the N=4 SYM plasma at strong coupling

Within the framework of the AdS/CFT correspondence, we study the time evolution of an energetic R-current propagating through a finite temperature, strongly coupled, N=4 SYM plasma and propose a physical picture for our results. In this picture, the current splits into a pair of massless partons, which then evolve via successive branchings, in such a way that energy is quasi-democratically divided among the products of a branching. We point out a duality between the transverse size of the partonic system produced through branching and the radial distance traveled by the dual Maxwell wave in the AdS geometry. For a time-like current, the branching occurs already in the vacuum, where it gives rise to a system of low-momentum partons isotropically distributed in the transverse plane. But at finite temperature, the branching mechanism is modified by the medium, in that the rate for parton splitting is enhanced by the transfer of transverse momentum from the partons to the plasma. This mechanism, which controls the parton energy loss, is sensitive to the energy density in the plasma, but not to the details of the thermal state. We compute the lifetime of the current for various kinematical regimes and provide physical interpretations for other, related, quantities, so like the meson screening length, the drag force, or the trailing string, that were previously computed via AdS/CFT techniques.Comment: 37 pages, 4 figure

Effect of surgical volume on short-term outcomes of cytoreductive surgery for advanced-stage ovarian cancer:A population-based study from the Dutch Gynecological Oncology Audit

Objective: Despite lacking clinical data, the Dutch government is considering increasing the minimum annual surgical volume per center from twenty to fifty cytoreductive surgeries (CRS) for advanced-stage ovarian cancer (OC). This study aims to evaluate whether this increase is warranted. Methods: This population-based study included all CRS for FIGO-stage IIB-IVB OC registered in eighteen Dutch hospitals between 2019 and 2022. Short-term outcomes included result of CRS, length of stay, severe complications, 30-day mortality, time to adjuvant chemotherapy, and textbook outcome. Patients were stratified by annual volume: low-volume (nine hospitals, &lt;25), medium-volume (four hospitals, 29–37), and high-volume (five hospitals, 54–84). Descriptive statistics and multilevel logistic regressions were used to assess the (case-mix adjusted) associations of surgical volume and outcomes. Results: A total of 1646 interval CRS (iCRS) and 789 primary CRS (pCRS) were included. No associations were found between surgical volume and different outcomes in the iCRS cohort. In the pCRS cohort, high-volume was associated with increased complete CRS rates (aOR 1.9, 95%-CI 1.2–3.1, p = 0.010). Furthermore, high-volume was associated with increased severe complication rates (aOR 2.3, 1.1–4.6, 95%-CI 1.3–4.2, p = 0.022) and prolonged length of stay (aOR 2.3, 95%-CI 1.3–4.2, p = 0.005). 30-day mortality, time to adjuvant chemotherapy, and textbook outcome were not associated with surgical volume in the pCRS cohort. Subgroup analyses (FIGO-stage IIIC-IVB) showed similar results. Various case-mix factors significantly impacted outcomes, warranting case-mix adjustment. Conclusions: Our analyses do not support further centralization of iCRS for advanced-stage OC. High-volume was associated with higher complete pCRS, suggesting either a more accurate selection in these hospitals or a more aggressive approach. The higher completeness rates were at the expense of higher severe complications and prolonged admissions.</p