Growth Histories in Bimetric Massive Gravity

We perform cosmological perturbation theory in Hassan-Rosen bimetric gravity for general homogeneous and isotropic backgrounds. In the de Sitter approximation, we obtain decoupled sets of massless and massive scalar gravitational fluctuations. Matter perturbations then evolve like in Einstein gravity. We perturb the future de Sitter regime by the ratio of matter to dark energy, producing quasi-de Sitter space. In this more general setting the massive and massless fluctuations mix. We argue that in the quasi-de Sitter regime, the growth of structure in bimetric gravity differs from that of Einstein gravity.Comment: 28 pages + appendix, 11 figure

The relative balance of goal-directed and habitual behaviours in obsessive-compulsive disorder

Our decisions are based on parallel and competing systems of goal-directed and habitual learning, systems which can be impaired in pathological behaviours. Here we focus on the influence of motivation and compare reward and loss outcomes in subjects with obsessive-compulsive disorder (OCD) on model-based goal-directed and model-free habitual behaviours using the two-step task. We further investigate the relationship with acquisition learning using a one-step probabilistic learning task. Forty-eight OCD subjects and 96 healthy volunteers were tested on a reward and 30 OCD subjects and 53 healthy volunteers on the loss version of the two-step task. Thirty-six OCD subjects and 72 healthy volunteers were also tested on a one-step reversal task. OCD subjects compared with healthy volunteers were less goal oriented (model-based) and more habitual (model-free) to reward outcomes with a shift towards greater model-based and lower habitual choices to loss outcomes. OCD subjects also had enhanced acquisition learning to loss outcomes on the one-step task, which correlated with goal-directed learning in the two-step task. OCD subjects had greater stay behaviours or perseveration in the one-step task irrespective of outcome. Compulsion severity was correlated with habitual learning in the reward condition. Obsession severity was correlated with greater switching after loss outcomes. In healthy volunteers, we further show that greater reward magnitudes are associated with a shift towards greater goal-directed learning further emphasizing the role of outcome salience. Our results highlight an important influence of motivation on learning processes in OCD and suggest that distinct clinical strategies based on valence may be warranted.The study was funded through a Wellcome Trust Intermediate Clinical Fellowship for VV (093705/Z/10/Z).This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/tp.2015.16

Cognitive-behavioral therapy for body dysmorphic disorder: A systematic review and meta-analysis of randomized controlled trials

Body dysmorphic disorder (BDD) is a chronic and disabling psychiatric disorder unlikely to remit without treatment. A systematic review and meta-analysis of randomized controlled trials (RCTs) of cognitive-behavioral therapy (CBT) for BDD was conducted, including published and unpublished trials to 26th November 2015. Primary outcomes were validated BDD measures; secondary outcomes included depression and insight. Meta-regressions were conducted to examine potential effects of variables on the primary outcome, including socio-demographic variables, comorbidity, symptom severity/duration, concomitant medication, treatment duration, and methodological quality of the RCTs. Seven RCTs (N = 299) met inclusion criteria. CBT was superior to waitlist or credible psychological placebo in reducing BDD (7 studies; delta = − 1.22, 95% CI = − 1.66 to − 0.79) and depression symptoms (5 studies; delta = − 0.49, 95% CI = − 0.76 to − 0.22). CBT was associated with improvements in insight/delusionality (4 studies; delta = − 0.56, 95% CI = − 0.93 to − 0.19). Improvement in BDD was maintained after 2–4 months follow-up (3 studies; delta = − 0.89, 95% CI = − 1.24 to − 0.54). Meta-regression analyses did not reveal any significant predictors of outcome. CBT is an efficacious treatment for BDD but there is substantial room for improvement. The specificity and long-term effects of CBT for BDD require further evaluation using credible control conditions. Additional trials comparing CBT with pharmacological therapies, as well as their combination, are warranted. Tele-care options, such as Internet-based CBT, hold great promise to increase access to evidence-based treatment for a majority of patients who need it and should be evaluated further

The association between body dysmorphic symptoms and suicidality among adolescents and young adults: A genetically informative study

BACKGROUND: Previous research indicates that body dysmorphic disorder (BDD) is associated with risk of suicidality. However, studies have relied on small and/or specialist samples and largely focussed on adults, despite these difficulties commonly emerging in youth. Furthermore, the aetiology of the relationship remains unknown. METHODS: Two independent twin samples were identified through the Child and Adolescent Twin Study in Sweden, at ages 18 (N = 6027) and 24 (N = 3454). Participants completed a self-report measure of BDD symptom severity. Young people and parents completed items assessing suicidal ideation/behaviours. Logistic regression models tested the association of suicidality outcomes with: (a) probable BDD, classified using an empirically derived cut-off; and (b) continuous scores of BDD symptoms. Bivariate genetic models examined the aetiology of the association between BDD symptoms and suicidality at both ages. RESULTS: Suicidal ideation and behaviours were common among those with probable BDD at both ages. BDD symptoms, measured continuously, were linked with all aspects of suicidality, and associations generally remained significant after adjusting for depressive and anxiety symptoms. Genetic factors accounted for most of the covariance between BDD symptoms and suicidality (72.9 and 77.7% at ages 18 and 24, respectively), but with significant non-shared environmental influences (27.1 and 22.3% at ages 18 and 24, respectively). CONCLUSIONS: BDD symptoms are associated with a substantial risk of suicidal ideation and behaviours in late adolescence and early adulthood. This relationship is largely explained by common genetic liability, but non-shared environmental effects are also significant and could provide opportunities for prevention among those at high-risk

Cosmological Solutions in Bimetric Gravity and their Observational Tests

We obtain the general cosmological evolution equations for a classically consistent theory of bimetric gravity. Their analytic solutions are demonstrated to generically allow for a cosmic evolution starting out from a matter dominated FLRW universe while relaxing towards a de Sitter (anti-de Sitter) phase at late cosmic time. In particular, we examine a subclass of models which contain solutions that are able to reproduce the expansion history of the cosmic concordance model inspite of the nonlinear couplings of the two metrics. This is demonstrated explicitly by fitting these models to observational data from Type Ia supernovae, Cosmic Microwave Background and Baryon Acoustic Oscillations.Comment: Latex, 26 pages. References added and minor revision of introduction and appendix

Crossing borders to bind proteins—a new concept in protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set

A new concept for protein recognition and binding is highlighted. The conjugation of small organic molecules or short peptides to polypeptides from a designed set provides binder molecules that bind proteins with high affinities, and with selectivities that are equal to those of antibodies. The small organic molecules or peptides need to bind the protein targets but only with modest affinities and selectivities, because conjugation to the polypeptides results in molecules with dramatically improved binder performance. The polypeptides are selected from a set of only sixteen sequences designed to bind, in principle, any protein. The small number of polypeptides used to prepare high-affinity binders contrasts sharply with the huge libraries used in binder technologies based on selection or immunization. Also, unlike antibodies and engineered proteins, the polypeptides have unordered three-dimensional structures and adapt to the proteins to which they bind. Binder molecules for the C-reactive protein, human carbonic anhydrase II, acetylcholine esterase, thymidine kinase 1, phosphorylated proteins, the D-dimer, and a number of antibodies are used as examples to demonstrate that affinities are achieved that are higher than those of the small molecules or peptides by as much as four orders of magnitude. Evaluation by pull-down experiments and ELISA-based tests in human serum show selectivities to be equal to those of antibodies. Small organic molecules and peptides are readily available from pools of endogenous ligands, enzyme substrates, inhibitors or products, from screened small molecule libraries, from phage display, and from mRNA display. The technology is an alternative to established binder concepts for applications in drug development, diagnostics, medical imaging, and protein separation

Mapping the physiography of Michigan with GIS

Abstract: We present a new physiographic map of Michigan, that is also available interactively, online. Only four, small-scale physiographic maps of Michigan had been previously published. Our mapping project made use of a wide variety of spatial data, in a GIS environment, to visualize and delineate the physical landscape in more detail than has been done previously. We also examined many of the unit boundaries in the field, using a GIS running on a GPS-enabled laptop. Unlike previous physiographic maps, the online version of the map enables users to query the criteria used to define each of the 224 boundaries of its 10 major and 91 minor physiographic units. The interactive nature of the online version of the map is a unique enhancement to physiographic maps and mapping. Our study also provides data on the number and types of criteria used to define each of the 224 unit boundaries within the map. Most of our unit boundaries are based on data derived from 10-m raster elevation data and NRCS soils data, e.g., relief, soil wetness, escarpments, landscape fabric, and parent material characteristics. Data gleaned from NRCS SSURGO county-scale soil maps were a strength of the project

Disorders of compulsivity: a common bias towards learning habits.

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.This study was funded by the WT fellowship grant for VV (093705/Z/ 10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. YW is supported by the Fyssen Fondation and MRC Studentships. PD is supported by the Gatsby Charitable Foundation. JEG has received grants from the National Institute of Drug Abuse and the National Center for Responsible Gaming. TWR and BJS are supported on a WT Programme Grant (089589/Z/09/Z). The BCNI is supported by a WT and MRC grant.This is the final published version. It's also available from Molecular Psychiatry at http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201444a.html