Quantization of Midisuperspace Models

We give a comprehensive review of the quantization of midisuperspace models. Though the main focus of the paper is on quantum aspects, we also provide an introduction to several classical points related to the definition of these models. We cover some important issues, in particular, the use of the principle of symmetric criticality as a very useful tool to obtain the required Hamiltonian formulations. Two main types of reductions are discussed: those involving metrics with two Killing vector fields and spherically symmetric models. We also review the more general models obtained by coupling matter fields to these systems. Throughout the paper we give separate discussions for standard quantizations using geometrodynamical variables and those relying on loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit

Indicators of breast cancer severity and appropriateness of surgery based on hospital administrative data in the Lazio Region, Italy

BACKGROUND: Administrative data can serve as an easily available source for epidemiological and evaluation studies. The aim of this study is to evaluate the use of hospital administrative data to determine breast cancer severity and the appropriateness of surgical treatment. METHODS: the study population consisted of 398 patients randomly selected from a cohort of women hospitalized for first-time breast cancer surgery in the Lazio Region, Italy. Tumor severity was defined in three different ways: 1) tumor size; 2) clinical stage (TNM); 3) severity indicator based on HIS data (SI). Sensitivity, specificity, and positive predictive value (PPV) of the severity indicator in evaluating appropriateness of surgery were calculated. The accuracy of HIS data was measured using Kappa statistic. RESULTS: Most of 387 cases were classified as T1 and T2 (tumor size), more than 70% were in stage I or II and the SI classified 60% of cases in medium-low category. Variation from guidelines indications identified under and over treatments. The accuracy of the SI to predict under-treatment was relatively good (58% of all procedures classified as under-treatment using pT where also classified as such using SI), and even greater predicting over-treatment (88.2% of all procedures classified as over treatment using pT where also classified as such using SI). Agreement between clinical chart and hospital discharge reports was K = 0.35. CONCLUSION: Our findings suggest that administrative data need to be used with caution when evaluating surgical appropriateness, mainly because of the limited ability of SI to predict tumor size and the questionable quality of HIS data as observed in other studies

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

Recent improvements in the development of A2B adenosine receptor agonists

Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1Ki = 1050 nM, hA2AKi = 1550 nM, hA2B EC50 = 82 nM, hA3Ki > 5 μM) and its 2-chloro analogue 23 (hA1Ki = 3500 nM, hA2AKi = 4950 nM, hA2B EC50 = 210 nM, hA3Ki > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary artery disorders and atherosclerosis

Quantitative trait locus analysis identifies Gabra3 as a regulator of behavioral despair in mice

The Tail Suspension Test (TST), which measures behavioral despair, is widely used as an animal model of human depressive disorders and antidepressant efficacy. In order to identify novel genes involved in the regulation of TST performance, we crossed an inbred strain exhibiting low immobility in the TST (RIIIS/J) with two high-immobility strains (C57BL/6J and NZB/BlNJ) to create two distinct F2 hybrid populations. All F2 offspring (n = 655) were genotyped at high density with a panel of SNP markers. Whole-genome interval mapping of the F2 populations identified statistically significant quantitative trait loci (QTLs) on mouse chromosomes (MMU) 4, 6, and X. Microarray analysis of hippocampal gene expression in the three parental strains was used to identify potential candidate genes within the MMUX QTLs identified in the NZB/BlNJ × RIIIS/J cross. Expression of Gabra3, which encodes the GABAA receptor α3 subunit, was robust in the hippocampus of B6 and RIIIS mice but absent from NZB hippocampal tissue. To verify the role of Gabra3 in regulating TST behavior in vivo, mice were treated with SB-205384, a positive modulator of the α3 subunit. SB-205384 significantly reduced TST immobility in B6 mice without affecting general activity, but it had no effect on behavior in NZB mice. This work suggests that GABRA3 regulates a behavioral endophenotype of depression and establishes this gene as a viable new target for the study and treatment of human depression

Evolutionary Changes in the Complexity of the Tectum of Nontetrapods: A Cladistic Approach

Background: The tectum is a structure localized in the roof of the midbrain in vertebrates, and is taken to be highly conserved in evolution. The present article assessed three hypotheses concerning the evolution of lamination and citoarchitecture of the tectum of nontetrapod animals: 1) There is a significant degree of phylogenetic inertia in both traits studied (number of cellular layers and number of cell classes in tectum); 2) Both traits are positively correlated accross evolution after correction for phylogeny; and 3) Different developmental pathways should generate different patterns of lamination and cytoarchitecture. Methodology/Principal Findings: The hypotheses were tested using analytical-computational tools for phylogenetic hypothesis testing. Both traits presented a considerably large phylogenetic signal and were positively associated. However, no difference was found between two clades classified as per the general developmental pathways of their brains. Conclusions/Significance: The evidence amassed points to more variation in the tectum than would be expected by phylogeny in three species from the taxa analysed; this variation is not better explained by differences in the main course of development, as would be predicted by the developmental clade hypothesis. Those findings shed new light on th

Cytochrome P450 1A2 (CYP1A2) activity, mammographic density, and oxidative stress: a cross-sectional study

INTRODUCTION: Mammographically dense breast tissue is a strong predictor of breast cancer risk, and is influenced by both mitogens and mutagens. One enzyme that is able to affect both the mitogenic and mutagenic characteristics of estrogens is cytochrome P450 1A2 (CYP1A2), which is principally responsible for the metabolism of 17β-estradiol. METHODS: In a cross-sectional study of 146 premenopausal and 149 postmenopausal women, we examined the relationships between CYP1A2 activity, malondialdehyde (MDA) levels, and mammographic density. In vivo CYP1A2 activity was assessed by measuring caffeine metabolites in urine. Levels of serum and urinary MDA, and MDA–deoxyguanosine adducts in DNA were measured. Mammograms were digitized and measured using a computer-assisted method. RESULTS: CYP1A2 activity in postmenopausal women, but not in premenopausal women, was positively associated with mammographic density, suggesting that increased CYP1A2 activity after the menopause is a risk factor for breast cancer. In premenopausal women, but not in postmenopausal women, CYP1A2 activity was positively associated with serum and urinary MDA levels; there was also some evidence that CYP1A2 activity was more positively associated with percentage breast density when MDA levels were high, and more negatively associated with percentage breast density when MDA levels were low. CONCLUSION: These findings provide further evidence that variation in the activity level of enzymes involved in estrogen metabolism is related to levels of mammographic density and potentially to breast cancer risk