Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms

BACKGROUND: The assessment of tumor invasion of underlying benign stroma in neoplastic squamous proliferation of the larynx may pose a diagnostic challenge, particularly in small biopsy specimens that are frequently tangentially sectioned. We studied whether thresholds of an eosinophilic response to laryngeal squamous neoplasms provides an adjunctive histologic criterion for determining the presence of invasion. METHODS: Eighty-seven(n = 87) cases of invasive squamous cell carcinoma and preinvasive squamous neoplasia were evaluated. In each case, the number of eosinophils per high power field(eosinophils/hpf), and per 10 hpf in the tissue adjacent to the neoplastic epithelium, were counted and tabulated. For statistical purposes, the elevated eosinophils were defined and categorized as: focally and moderately elevated (5–9 eos/hpf), focally and markedly increased(>10/hpf), diffusely and moderately elevated(5–19 eos/10hpf), and diffusely and markedly increased (>20/10hpf). RESULTS: In the invasive carcinoma, eosinophil counts were elevated focally and /or diffusely, more frequently seen than in non-invasive neoplastic lesions. The increased eosinophil counts, specifically >10hpf, and >20/10hpf, were all statistically significantly associated with stromal invasion. Greater than 10 eosinophils/hpf and/or >20 eosinophils/10hpf had highest predictive power, with a sensitivity, specificity and positive predictive value of 82%, 93%, 96% and 80%, 100% and 100%, respectively. Virtually, greater than 20 eosinophils/10 hpf was diagnostic for tumor invasion in our series. CONCLUSION: Our study suggests for the first time that the elevated eosinophil count in squamous neoplasia of the larynx is a morphologic feature associated with tumor invasion. When the number of infiltrating eosinophils exceeds 10/hpf and or >20/10 hpf in a laryngeal biopsy with squamous neoplasia, it represents an indicator for the possibility of tumor invasion. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should prompt a thorough evaluation for invasiveness, when evidence of invasion is absent, or when invasion is suspected by conventional criteria in the initial sections

Holography at an Extremal De Sitter Horizon

Rotating maximal black holes in four-dimensional de Sitter space, for which the outer event horizon coincides with the cosmological horizon, have an infinite near-horizon region described by the rotating Nariai metric. We show that the asymptotic symmetry group at the spacelike future boundary of the near-horizon region contains a Virasoro algebra with a real, positive central charge. This is evidence that quantum gravity in a rotating Nariai background is dual to a two-dimensional Euclidean conformal field theory. These results are related to the Kerr/CFT correspondence for extremal black holes, but have two key differences: one of the black hole event horizons has been traded for the cosmological horizon, and the near-horizon geometry is a fiber over dS_2 rather than AdS_2.Comment: 15 page

Constraining noncommutative field theories with holography

An important window to quantum gravity phenomena in low energy noncommutative (NC) quantum field theories (QFTs) gets represented by a specific form of UV/IR mixing. Yet another important window to quantum gravity, a holography, manifests itself in effective QFTs as a distinct UV/IR connection. In matching these two principles, a useful relationship connecting the UV cutoff $\Lambda_{\rm UV}$, the IR cutoff $\Lambda_{\rm IR}$ and the scale of noncommutativity $\Lambda_{\rm NC}$, can be obtained. We show that an effective QFT endowed with both principles may not be capable to fit disparate experimental bounds simultaneously, like the muon $g-2$ and the masslessness of the photon. Also, the constraints from the muon $g-2$ preclude any possibility to observe the birefringence of the vacuum coming from objects at cosmological distances. On the other hand, in NC theories without the UV completion, where the perturbative aspect of the theory (obtained by truncating a power series in $\Lambda_{\rm NC}^{-2}$) becomes important, a heuristic estimate of the region where the perturbative expansion is well-defined $E/ \Lambda_{\rm NC} \lesssim 1$, gets affected when holography is applied by providing the energy of the system $E$ a $\Lambda_{\rm NC}$-dependent lower limit. This may affect models which try to infer the scale $\Lambda_{\rm NC}$ by using data from low-energy experiments.Comment: 4 pages, version to be published in JHE

Lowe syndrome

Lowe syndrome (the oculocerebrorenal syndrome of Lowe, OCRL) is a multisystem disorder characterised by anomalies affecting the eye, the nervous system and the kidney. It is a uncommon, panethnic, X-linked disease, with estimated prevalence in the general population of approximately 1 in 500,000. Bilateral cataract and severe hypotonia are present at birth. In the subsequent weeks or months, a proximal renal tubulopathy (Fanconi-type) becomes evident and the ocular picture may be complicated by glaucoma and cheloids. Psychomotor retardation is evident in childhood, while behavioural problems prevail and renal complications arise in adolescence. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate 5 phosphatase, PtdIns (4,5)P2, in the trans-Golgi network is responsible for the disease. Both enzymatic and molecular testing are available for confirmation of the diagnosis and for prenatal detection of the disease. The treatment includes: cataract extraction, glaucoma control, physical and speech therapy, use of drugs to address behavioural problems, and correction of the tubular acidosis and the bone disease with the use of bicarbonate, phosphate, potassium and water. Life span rarely exceeds 40 years

Social–ecological mismatches create conservation challenges in introduced species management

This is the final version. Available from the Ecological Society of America via the DOI in this recordIntroduced species can have important effects on the component species and processes of native ecosystems. However, effective introduced species management can be complicated by technical and social challenges. We identify “social–ecological mismatches” (that is, differences between the scales and functioning of interacting social and ecological systems) as one such challenge. We present three case studies in which mismatches between the organization and functioning of key social and ecological systems have contributed to controversies and debates surrounding introduced species management and policy. We identify three common issues: social systems and cultures may adapt to a new species’ arrival at a different rate than ecosystems; ecological impacts can arise at one spatial scale while social impacts occur at another; and the effects of introduced species can spread widely, whereas management actions are constrained by organizational and/or political boundaries. We propose strategies for collaborative knowledge building and adaptive management that may help address these challenges

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Heterotypic interactions drive antibody synergy against a malaria vaccine candidate

Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets

The holographic principle

There is strong evidence that the area of any surface limits the information content of adjacent spacetime regions, at 10^(69) bits per square meter. We review the developments that have led to the recognition of this entropy bound, placing special emphasis on the quantum properties of black holes. The construction of light-sheets, which associate relevant spacetime regions to any given surface, is discussed in detail. We explain how the bound is tested and demonstrate its validity in a wide range of examples. A universal relation between geometry and information is thus uncovered. It has yet to be explained. The holographic principle asserts that its origin must lie in the number of fundamental degrees of freedom involved in a unified description of spacetime and matter. It must be manifest in an underlying quantum theory of gravity. We survey some successes and challenges in implementing the holographic principle.Comment: 52 pages, 10 figures, invited review for Rev. Mod. Phys; v2: reference adde

AdS_3/LCFT_2 - Correlators in Cosmological Topologically Massive Gravity

For cosmological topologically massive gravity at the chiral point we calculate momentum space 2- and 3-point correlators of operators in the postulated dual CFT on the cylinder. These operators are sourced by the bulk and boundary gravitons. Our correlators are fully consistent with the proposal that cosmological topologically massive gravity at the chiral point is dual to a logarithmic CFT. In the process we give a complete classification of normalizable and non-normalizeable left, right and logarithmic solutions to the linearized equations of motion in global AdS_3.Comment: 39 pages + appendices, 1 eps figure, v2: minor changes in text in 4.1.2, corrected typo in (2.31

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed