On the Geometry and Mass of Static, Asymptotically AdS Spacetimes, and the Uniqueness of the AdS Soliton

We prove two theorems, announced in hep-th/0108170, for static spacetimes that solve Einstein's equation with negative cosmological constant. The first is a general structure theorem for spacetimes obeying a certain convexity condition near infinity, analogous to the structure theorems of Cheeger and Gromoll for manifolds of non-negative Ricci curvature. For spacetimes with Ricci-flat conformal boundary, the convexity condition is associated with negative mass. The second theorem is a uniqueness theorem for the negative mass AdS soliton spacetime. This result lends support to the new positive mass conjecture due to Horowitz and Myers which states that the unique lowest mass solution which asymptotes to the AdS soliton is the soliton itself. This conjecture was motivated by a nonsupersymmetric version of the AdS/CFT correspondence. Our results add to the growing body of rigorous mathematical results inspired by the AdS/CFT correspondence conjecture. Our techniques exploit a special geometric feature which the universal cover of the soliton spacetime shares with familiar ``ground state'' spacetimes such as Minkowski spacetime, namely, the presence of a null line, or complete achronal null geodesic, and the totally geodesic null hypersurface that it determines. En route, we provide an analysis of the boundary data at conformal infinity for the Lorentzian signature static Einstein equations, in the spirit of the Fefferman-Graham analysis for the Riemannian signature case. This leads us to generalize to arbitrary dimension a mass definition for static asymptotically AdS spacetimes given by Chru\'sciel and Simon. We prove equivalence of this mass definition with those of Ashtekar-Magnon and Hawking-Horowitz.Comment: Accepted version, Commun Math Phys; Added Remark IV.3 and supporting material dealing with non-uniqueness arising from choice of special cycle on the boundary at infinity; 2 new citations added; LaTeX 27 page

Holographic Reconstruction and Renormalization in Asymptotically Ricci-flat Spacetimes

In this work we elaborate on an extension of the AdS/CFT framework to a subclass of gravitational theories with vanishing cosmological constant. By building on earlier ideas, we construct a correspondence between Ricci-flat spacetimes admitting asymptotically hyperbolic hypersurfaces and a family of conformal field theories on a codimension two manifold at null infinity. By truncating the gravity theory to the pure gravitational sector, we find the most general spacetime asymptotics, renormalize the gravitational action, reproduce the holographic stress tensors and Ward identities of the family of CFTs and show how the asymptotics is mapped to and reconstructed from conformal field theory data. In even dimensions, the holographic Weyl anomalies identify the bulk time coordinate with the spectrum of central charges with characteristic length the bulk Planck length. Consistency with locality in the bulk time direction requires a notion of locality in this spectrum.Comment: 44 pages, 4 figures. v2: minor changes in section

Exercise and Caloric Restriction Alter the Immune System of Mice Submitted to a High-Fat Diet

As the size of adipocytes increases during obesity, the establishment of resident immune cells in adipose tissue becomes an important source of proinflammatory mediators. Exercise and caloric restriction are two important, nonpharmacological tools against body mass increase. To date, their effects on the immune cells of adipose tissue in obese organisms, specifically when a high-fat diet is consumed, have been poorly investigated. Thus, after consuming a high-fat diet, mice were submitted to chronic swimming training or a 30% caloric restriction in order to investigate the effects of both interventions on resident immune cells in adipose tissue. These strategies were able to reduce body mass and resulted in changes in the number of resident immune cells in the adipose tissue and levels of cytokines/chemokines in serum. While exercise increased the number of NK cells in adipose tissue and serum levels of IL-6 and RANTES, caloric restriction increased the CD4+/CD8+ cell ratio and MCP-1 levels. Together, these data demonstrated that exercise and caloric restriction modulate resident immune cells in adipose tissues differently in spite of an equivalent body weight reduction. Additionally, the results also reinforce the idea that a combination of both strategies is better than either individually for combating obesity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniv São Paulo, Sch Arts Sci & Humanities, BR-03828000 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Lab Transplantat Immunobiol, Dept Immunol, BR-05508900 São Paulo, BrazilUniv Fed Pelotas, Sch Nutr, Dept Nutr, BR-96010610 Pelotas, RS, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilFAPESP: 2011/03528-0Web of Scienc

Increasing Dominance - the Role of Advertising, Pricing and Product Design

Despite the empirical relevance of advertising strategies in concentrated markets, the economics literature is largely silent on the effect of persuasive advertising strategies on pricing, market structure and increasing (or decreasing) dominance. In a simple model of persuasive advertising and pricing with differentiated goods, we analyze the interdependencies between ex-ante asymmetries in consumer appeal, advertising and prices. Products with larger initial appeal to consumers will be advertised more heavily but priced at a higher level - that is, advertising and price discounts are strategic substitutes for products with asymmetric initial appeal. We find that the escalating effect of advertising dominates the moderating effect of pricing so that post-competition market shares are more asymmetric than pre-competition differences in consumer appeal. We further find that collusive advertising (but competitive pricing) generates the same market outcomes, and that network effects lead to even more extreme market outcomes, both directly and via the effect on advertising

Doping the holographic Mott insulator

Mott insulators form because of strong electron repulsions, being at the heart of strongly correlated electron physics. Conventionally these are understood as classical "traffic jams" of electrons described by a short-ranged entangled product ground state. Exploiting the holographic duality, which maps the physics of densely entangled matter onto gravitational black hole physics, we show how Mott-insulators can be constructed departing from entangled non-Fermi liquid metallic states, such as the strange metals found in cuprate superconductors. These "entangled Mott insulators" have traits in common with the "classical" Mott insulators, such as the formation of Mott gap in the optical conductivity, super-exchange-like interactions, and form "stripes" when doped. They also exhibit new properties: the ordering wave vectors are detached from the number of electrons in the unit cell, and the DC resistivity diverges algebraically instead of exponentially as function of temperature. These results may shed light on the mysterious ordering phenomena observed in underdoped cuprates.Comment: 27 pages, 9 figures. Accepted in Nature Physic

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Development and Characterization of Synthetic Glucopyranosyl Lipid Adjuvant System as a Vaccine Adjuvant

Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR) 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA). We assessed the effects of GLA on murine and human dendritic cells (DC) by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL) on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC). When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative TH1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants

Conformal Lifshitz Gravity from Holography

We show that holographic renormalization of relativistic gravity in asymptotically Lifshitz spacetimes naturally reproduces the structure of gravity with anisotropic scaling: The holographic counterterms induced near anisotropic infinity take the form of the action for gravity at a Lifshitz point, with the appropriate value of the dynamical critical exponent $z$. In the particular case of 3+1 bulk dimensions and $z=2$ asymptotic scaling near infinity, we find a logarithmic counterterm, related to anisotropic Weyl anomaly of the dual CFT, and show that this counterterm reproduces precisely the action of conformal gravity at a $z=2$ Lifshitz point in 2+1 dimensions, which enjoys anisotropic local Weyl invariance and satisfies the detailed balance condition. We explain how the detailed balance is a consequence of relations among holographic counterterms, and point out that a similar relation holds in the relativistic case of holography in $AdS_5$. Upon analytic continuation, analogous to the relativistic case studied recently by Maldacena, the action of conformal gravity at the $z=2$ Lifshitz point features in the ground-state wavefunction of a gravitational system with an interesting type of spatial anisotropy.Comment: 41 pages; v2: typos corrected, references adde

Weyl Cohomology and the Effective Action for Conformal Anomalies

We present a general method of deriving the effective action for conformal anomalies in any even dimension, which satisfies the Wess-Zumino consistency condition by construction. The method relies on defining the coboundary operator of the local Weyl group, and giving a cohomological interpretation to counterterms in the effective action in dimensional regularization with respect to this group. Non-trivial cocycles of the Weyl group arise from local functionals that are Weyl invariant in and only in the physical even integer dimension. In the physical dimension the non-trivial cocycles generate covariant non-local action functionals characterized by sensitivity to global Weyl rescalings. The non-local action so obtained is unique up to the addition of trivial cocycles and Weyl invariant terms, both of which are insensitive to global Weyl rescalings. These distinct behaviors under rigid dilations can be used to distinguish between infrared relevant and irrelevant operators in a generally covariant manner. Variation of the $d=4$ non-local effective action yields two new conserved geometric stress tensors with local traces. The method may be extended to any even dimension by making use of the general construction of conformal invariants given by Fefferman and Graham. As a corollary, conformal field theory behavior of correlators at the asymptotic infinity of either anti-de Sitter or de Sitter spacetimes follows, i.e. AdS$_{d+1}$ or deS$_{d+1}$/CFT$_d$ correspondence. The same construction naturally selects all infrared relevant terms (and only those terms) in the low energy effective action of gravity in any even integer dimension. The infrared relevant terms arising from the known anomalies in d=4 imply that the classical Einstein theory is modified at large distances.Comment: 32 pages. LateX file. LateX twic

Non-invasive management of peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is common and symptoms can be debilitating and lethal. Risk management, exercise, radiological and surgical intervention are all valuable therapies, but morbidity and mortality rates from this disease are increasing. Circulatory enhancement can be achieved using simple medical electronic devices, with claims of minimal adverse side effects. The evidence for these is variable, prompting a review of the available literature. METHODS: Embase and Medline were interrogated for full text articles in humans and written in English. Any external medical devices used in the management of peripheral arterial disease were included if they had objective outcome data. RESULTS: Thirty-one papers met inclusion criteria, but protocols were heterogenous. The medical devices reported were intermittent pneumatic compression (IPC), electronic nerve (NMES) or muscle stimulators (EMS), and galvanic electrical dressings. In patients with intermittent claudication, IPC devices increase popliteal artery velocity (49-70 %) and flow (49-84 %). Gastrocnemius EMS increased superficial femoral artery flow by 140 %. Over 4.5-6 months IPC increased intermittent claudication distance (ICD) (97-150 %) and absolute walking distance (AWD) (84-112 %), with an associated increase in quality of life. NMES of the calf increased ICD and AWD by 82 % and 61-150 % at 4 weeks, and 26 % and 34 % at 8 weeks. In patients with critical limb ischaemia IPC reduced rest pain in 40-100 % and was associated with ulcer healing rates of 26 %. IPC had an early limb salvage rate of 58-83 % at 1-3 months, and 58-94 % at 1.5-3.5 years. No studies have reported the use of EMS or NMES in the management of CLI. CONCLUSION: There is evidence to support the use of IPC in the management of claudication and CLI. There is a building body of literature to support the use of electrical stimulators in PAD, but this is low level to date. Devices may be of special benefit to those with limited exercise capacity, and in non-reconstructable critical limb ischaemia. Galvanic stimulation is not recommended