ACVIM Small Animal Consensus Recommendations on the Treatment and Prevention of Uroliths in Dogs and Cats.

In an age of advancing endoscopic and lithotripsy technologies, the management of urolithiasis poses a unique opportunity to advance compassionate veterinary care, not only for patients with urolithiasis but for those with other urinary diseases as well. The following are consensus-derived, research and experience-supported, patient-centered recommendations for the treatment and prevention of uroliths in dogs and cats utilizing contemporary strategies. Ultimately, we hope that these recommendations will serve as a foundation for ongoing and future clinical research and inspiration for innovative problem solving

Computational Psychiatry: towards a mathematically informed understanding of mental illness

Computational Psychiatry aims to describe the relationship between the brain's neurobiology, its environment and mental symptoms in computational terms. In so doing, it may improve psychiatric classification and the diagnosis and treatment of mental illness. It can unite many levels of description in a mechanistic and rigorous fashion, while avoiding biological reductionism and artificial categorisation. We describe how computational models of cognition can infer the current state of the environment and weigh up future actions, and how these models provide new perspectives on two example disorders, depression and schizophrenia. Reinforcement learning describes how the brain can choose and value courses of actions according to their long-term future value. Some depressive symptoms may result from aberrant valuations, which could arise from prior beliefs about the loss of agency ('helplessness'), or from an inability to inhibit the mental exploration of aversive events. Predictive coding explains how the brain might perform Bayesian inference about the state of its environment by combining sensory data with prior beliefs, each weighted according to their certainty (or precision). Several cortical abnormalities in schizophrenia might reduce precision at higher levels of the inferential hierarchy, biasing inference towards sensory data and away from prior beliefs. We discuss whether striatal hyperdopaminergia might have an adaptive function in this context, and also how reinforcement learning and incentive salience models may shed light on the disorder. Finally, we review some of Computational Psychiatry's applications to neurological disorders, such as Parkinson's disease, and some pitfalls to avoid when applying its methods

Anti-oxidative cellular protection effect of fasting-induced autophagy as a mechanism for hormesis

The aim of this investigation was to test the hypothesis that fasting-induced augmented lysosomal autophagic turnover of cellular proteins and organelles will reduce potentially harmful lipofuscin (age-pigment) formation in cells by more effectively removing oxidatively damaged proteins. An animal model (marine snail - common periwinkle, Littorina littorea) was used to experimentally test this hypothesis. Snails were deprived of algal food for 7 days to induce an augmented autophagic response in their hepatopancreatic digestive cells (hepatocyte analogues). This treatment resulted in a 25% reduction in the cellular content of lipofuscin in the digestive cells of the fasting animals in comparison with snails fed ad libitum on green alga (Ulva lactuca). Similar findings have previously been observed in the digestive cells of marine mussels subjected to copper-induced oxidative stress. Additional measurements showed that fasting significantly increased cellular health based on lysosomal membrane stability, and reduced lipid peroxidation and lysosomal/cellular triglyceride. These findings support the hypothesis that fasting-induced augmented autophagic turnover of cellular proteins has an anti-oxidative cytoprotective effect by more effectively removing damaged proteins, resulting in a reduction in the formation of potentially harmful proteinaceous aggregates such as lipofuscin. The inference from this study is that autophagy is important in mediating hormesis. An increase was demonstrated in physiological complexity with fasting, using graph theory in a directed cell physiology network (digraph) model to integrate the various biomarkers. This was commensurate with increased health status, and supportive of the hormesis hypothesis. The potential role of enhanced autophagic lysosomal removal of damaged proteins in the evolutionary acquisition of stress tolerance in intertidal molluscs is discussed and parallels are drawn with the growing evidence for the involvement of autophagy in hormesis and anti-ageing processes

Searching for an anchor in an unpredictable world: A computational model of obsessive compulsive disorder

In this article, we develop a computational model of obsessive–compulsive disorder (OCD). We propose that OCD is characterized by a difficulty in relying on past events to predict the consequences of patients’ own actions and the unfolding of possible events. Clinically, this corresponds both to patients’ difficulty in trusting their own actions (and therefore repeating them), and to their common preoccupation with unlikely chains of events. Critically, we develop this idea on the basis of the well-developed framework of the Bayesian brain, where this impairment is formalized as excessive uncertainty regarding state transitions. We illustrate the validity of this idea using quantitative simulations and use these to form specific empirical predictions. These predictions are evaluated in relation to existing evidence, and are used to delineate directions for future research. We show how seemingly unrelated findings and phenomena in OCD can be explained by the model, including a persistent experience that actions were not adequately performed and a tendency to repeat actions; excessive information gathering (i.e., checking); indecisiveness and pathological doubt; overreliance on habits at the expense of goal-directed behavior; and overresponsiveness to sensory stimuli, thoughts, and feedback. We discuss the relationship and interaction between our model and other prominent models of OCD, including models focusing on harm-avoidance, not-just-right experiences, or impairments in goal-directed behavior. Finally, we outline potential clinical implications and suggest lines for future research

Fermions and Type IIB Supergravity On Squashed Sasaki-Einstein Manifolds

We discuss the dimensional reduction of fermionic modes in a recently found class of consistent truncations of type IIB supergravity compactified on squashed five-dimensional Sasaki-Einstein manifolds. We derive the lower dimensional equations of motion and effective action, and comment on the supersymmetry of the resulting theory, which is consistent with N=4 gauged supergravity in $d=5$, coupled to two vector multiplets. We compute fermion masses by linearizing around two $AdS_{5}$ vacua of the theory: one that breaks N=4 down to N=2 spontaneously, and a second one which preserves no supersymmetries. The truncations under consideration are noteworthy in that they retain massive modes which are charged under a U(1) subgroup of the $R$-symmetry, a feature that makes them interesting for applications to condensed matter phenomena via gauge/gravity duality. In this light, as an application of our general results we exhibit the coupling of the fermions to the type IIB holographic superconductor, and find a consistent further truncation of the fermion sector that retains a single spin-1/2 mode.Comment: 43 pages, 2 figures, PDFLaTeX; v2: added references, typos corrected, minor change

Universality and exactness of Schrodinger geometries in string and M-theory

We propose an organizing principle for classifying and constructing Schrodinger-invariant solutions within string theory and M-theory, based on the idea that such solutions represent nonlinear completions of linearized vector and graviton Kaluza-Klein excitations of AdS compactifications. A crucial simplification, derived from the symmetry of AdS, is that the nonlinearities appear only quadratically. Accordingly, every AdS vacuum admits infinite families of Schrodinger deformations parameterized by the dynamical exponent z. We exhibit the ease of finding these solutions by presenting three new constructions: two from M5 branes, both wrapped and extended, and one from the D1-D5 (and S-dual F1-NS5) system. From the boundary perspective, perturbing a CFT by a null vector operator can lead to nonzero beta-functions for spin-2 operators; however, symmetry restricts them to be at most quadratic in couplings. This point of view also allows us to easily prove nonrenormalization theorems: for any Sch(z) solution of two-derivative supergravity constructed in the above manner, z is uncorrected to all orders in higher derivative corrections if the deforming KK mode lies in a short multiplet of an AdS supergroup. Furthermore, we find infinite classes of 1/4 BPS solutions with 4-,5- and 7-dimensional Schrodinger symmetry that are exact.Comment: 31 pages, plus appendices; v2, minor corrections, added refs, slight change in interpretation in section 2.3, new Schrodinger and Lifshitz solutions included; v3, clarifications in sections 2 and 3 regarding existence of solutions and multi-trace operator

The first polluted river? Repeated copper contamination of fluvial sediments associated with Late Neolithic human activity in southern Jordan

The roots of pyrometallurgy are obscure. This paper explores one possible precursor, in the Faynan Orefield in southern Jordan. There, at approximately 7000 cal. BP, banks of a near-perennial meandering stream (today represented by complex overbank wetland and anthropogenic deposits) were contaminated repeatedly by copper emitted by human activities. Variations in the distribution of copper in this sequence are not readily explained in other ways, although the precise mechanism of contamination remains unclear. The degree of copper enhancement was up to an order of magnitude greater than that measured in Pleistocene fluvial and paludal sediments, in contemporary or slightly older Holocene stream and pond deposits, and in the adjacent modern wadi braidplain. Lead is less enhanced, more variable, and appears to have been less influenced by contemporaneous human activities at this location. Pyrometallurgy in this region may have appeared as a byproduct of the activity practised on the stream-bank in the Wadi Faynan ~7000 years ago

Bosonic Fractionalisation Transitions

At finite density, charge in holographic systems can be sourced either by explicit matter sources in the bulk or by bulk horizons. In this paper we find bosonic solutions of both types, breaking a global U(1) symmetry in the former case and leaving it unbroken in the latter. Using a minimal bottom-up model we exhibit phase transitions between the two cases, under the influence of a relevant operator in the dual field theory. We also embed solutions and transitions of this type in M-theory, where, holding the theory at constant chemical potential, the cohesive phase is connected to a neutral phase of Schr\"odinger type via a z=2 QCP.Comment: references added. minor changes. version published in JHE

Lifshitz black holes in string theory

We provide the first black hole solutions with Lifshitz asymptotics found in string theory. These are expected to be dual to models enjoying anisotropic scale invariance with dynamical exponent z=2 at finite temperature. We employ a consistent truncation of type IIB supergravity to four dimensions with an arbitrary 5-dimensional Einstein manifold times a circle as internal geometry. New interesting features are found that significantly differ from previous results in phenomenological models. In particular, small black holes are shown to be thermodynamically unstable, analogously to the usual AdS-Schwarzschild black holes, and extremality is never reached. This signals a possible Hawking-Page like phase transition at low temperatures.Comment: 19 pages, 7 figures. v2 references adde