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BACKGROUND: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI.METHODS: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/- 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%).RESULTS: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%).CONCLUSIONS: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment.

A 65-year-old male patient with a history of Myelodysplastic Syndrome (MDS) and Systemic Mastocytosis (SM) presented with an invasive disease of the external auditory canal (EAC) and a parotid gland abscess. Abscess drainage and treatment for a malignant otitis externa (MOE) was started, which did not lead to clinical improvement. Computed Tomography (CT) of the petrous bone as well as a Positron Emission Tomography/Computed Tomography with 2-[fluorine-18]-fluoro-2-deoxy- d -glucose (FDG-PET-CT) showed bony erosion of the EAC with a symmetrical FDG distribution at the level of both EACs. Histopathological biopsies of the EAC revealed a rarely encountered localization of systemic mastocytosis (SM). Especially patients with a hematological disorder such as a MDS are at risk to develop SM. In case of a fulminant infectious disease of the EAC in these patients, a localization of SM should be considered as well. This is the first report on SM with a localization in the EAC.

A Schroedinger equation proposed for the GMP gapped spin-2 mode of fractional Quantum Hall states is found from a novel non-relativistic limit, applicable only in 2+1 dimensions, of the massive spin-2 Fierz-Pauli field equations. It is also found from a novel null reduction of the linearized Einstein field equations in 3+1 dimensions, and in this context a uniform distribution of spin-2 particles implies, via a Brinkmann-wave solution of the non-linear Einstein equations, a confining harmonic oscillator potential for the individual particles., Comment: 5 pages. Additional references, with discussion, in v2, plus improved analysis of parity violation

Summary The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7. Additionally immuno-stainings for p53, Cyclin D1 and (p)FADD expression were evaluated. Malignant progression was recorded. Eighteen patients with carcinoma in situ (CIS) were treated after diagnosis and excluded from follow-up. Chromosome instability was strongly associated with a high risk of malignant transformation, especially in lower grade lesions (hyperplasia, mild and moderate dysplasia; odds ratio = 8.4, p = 0.004). Patients with lesions containing chromosome instability showed a significantly worse 5-year progression-free survival than those with premalignancies without chromosome instability ( p = 0.002). Neither histopathology nor the protein markers predicted progression in univariate analysis, although histo-pathological diagnosis, p53 and FADD contributed positively to chromosome instability in multivariate analysis. Chromosome instability is associated with malignant progression of laryngeal premalignancies, especially in lower grade lesions. These results may contribute to better risk counselling, provided that they can be validated in a larger patient set.

We discuss branes whose world-volume dimension equals the target space-time dimension, i.e. "space-time-filling branes". In addition to the D9-branes, there are 9-branes in the NS-NS sectors of both the IIA and IIB strings. The world-volume actions of these branes are constructed, via duality, from the known actions of branes with codimension larger than zero. Each of these types of branes is used in the construction of a string theory with sixteen supercharges by modding out a Type II string by an appropriate discrete symmetry and adding 32 9-branes. These constructions are related by a web of dualities and each arises as a different Limit of the Horava-Witten construction. (C) 2000 Elsevier Science B.V. All rights reserved.

Contains fulltext : 125535.pdf (Publisher’s version ) (Open Access) OBJECTIVES: One of the main problems in reducing the incidence of oral squamous cell carcinoma (OSCC) is the inability to appropriately deal with leukoplakia. Accurately identifying lesions which will progress to malignancy is currently not possible. The present study aims to establish the value of chromosome instability (CI) detection by DNA image cytometry and FISH analysis for prognosis and monitoring of oral leukoplakia. MATERIALS AND METHODS: For this purpose, we included from our archives 102 oral leukoplakia cases, which had been diagnosed between 1991 and 2008. Patient follow-up data were collected and the histopathological diagnosis was revised. CI assessment was carried out on paraffin-embedded tissue sections using both DNA image cytometry (ICM) and dual target FISH for chromosomes 1 and 7. RESULTS: 16 of 102 Patients developed carcinoma in situ or OSCC. Both detection methods were found to yield prognostic information independent of the histopathological diagnosis. CI was a strong individual marker of progression, with hazard ratios (HRs) of 7.2 and 6.8 for ICM and FISH respectively. Moreover, this approach seems suitable for monitoring lesions over time (especially ICM). Combining histopathology and CI enables subdivision of patients into three risk groups, with different probabilities of malignant progression. CONCLUSION: CI detection seems a reliable method for risk assessment of oral premalignancies and its application may contribute to a better risk-counselling and appropriate treatment regimen or watchfull-waiting approach of patients.

The objective of this study is to measure interobserver variability in the classification of laryngeal mucosal premalignant lesions by reassessing the histopathology of previously diagnosed cases and to determine the possible therapeutic consequences of disagreement among observers. Histopathological assessment of 110 laryngeal mucosal premalignant lesions was done by three pathologists. Each slide had to be classified according to the World Health Organization, Squamous Intraepithelial Neoplasia, and the Ljubljana Squamous Intraepithelial Lesions systems. After the independent assessment, a joint meeting took place. To assess the relation between histopathological grading and subsequent clinical management, we created a two-and a three-grade system besides one comprising all options. For all analyses, the SAS/STAT statistical software was used. The highest unweighted kappa-values concerning the all-options system are observed for the Squamous Intraepithelial Neoplasia classification (0.28, 95% confidence interval 0.23-0.33), followed by the World Health Organization and Ljubljana classifications. For the two-grade system the Ljubljana classification shows the highest unweighted kappa-values (0.50, 95%, 0.39-0.61), followed by the World Health Organization and Squamous Intraepithelial Neoplasia classifications. For the three-grade system, the unweighted kappa-values are similar. The implementation of weighted kappa-values led to higher scores within all three classification systems, although these did not exceed 0.55 (moderate agreement). Given the high level of consensus, simultaneous pathological assessment may be said to provide added value in comparison with independent assessment. In the current study, no clear tendency is observed in favor of any one classification system. The proposed three-grade system could be an improved histopathological tool because it is easier to correlate with clinical decision making and because it yields better unweighted kappa-values and proportions of concordance than the all-options system. Furthermore, clinical management could benefit from assessment by more than one pathologist in suspected cases of dysplasia or carcinoma. Modern Pathology (2011) 24, 892-898; doi: 10.1038/modpathol.2011.50; published online 15 April 2011

This book is written for both physicists and mathematicians. It contains a detailed investigation of nonlinear extensions of two-dimensional conformal symmetries, i.e. the Virasoro symmetries. These extended conformal symmetries, generically called symmetries, generate so-called algebras which are defined by nonlinear relations. The algebras have attracted the attention of both physicists and mathematicians. From the mathematician's point of view they form interesting extensions of the usual linear algebras. From the physicist's point of view they could be used for the construction of new string theories in the same way that the Virasoro symmetries underlie the usual string theories. The book contains an overview of the author's work on the simplest example of a algebra: the algebra. For this special case many results are derived thereby clarifying the general case. Many explicit expressions are given, often via tables in the different appendices, that have sometimes been obtained by using a computer. In the introduction the authors first discuss the case of the linear Virasoro algebra to clarify and emphasize the common features of and the differences with the case of the nonlinear algebra. They discuss, in the first part of the book, the structure of the modules and use these results to compute (partly via conjectures) the semi-infinite cohomology of the algebra with values in the tensor product of c = 2 and c = 98 Fock modules. This case is relevant for the study of a noncritical string propagating in four dimensions. The second part of the book focuses on the geometrical structure underlying the operator cohomology. It turns out that this structure is described by Batalin - Vilkovisky (BV) algebras which have been introduced independently by mathematicians and physicists at around the same time. The authors first derive some general results on BV algebras. This part of the book can be read independently of the rest. They next discuss the BV algebra of the string that occurred in the first part of the book. The precise connection between the cohomology and the BV algebras is made via a claim which the authors themselves consider as perhaps the most important result in the book. In short, the authors are well able to present their results in a clear and precise way. I highly recommend this book both to the physicist who is interested in the precise mathematical properties of symmetries and to the mathematician who wants to learn more about the physical applications of algebras.

Purpose It is known that despite efforts of improving adequate ablation in head and neck cancer, the local recurrence rate has not decreased sufficiently over the last two decades. This is partly due to the presence of potentially malignant groups of cells in the resection margins (minimal residual disease). Chromosomal instability (CI) detection in these histologically diagnosed tumour-free margins might help predict patients at risk for recurrence. Material and methods We have included 25 patients with oral squamous cell carcinoma (OSCC) treated with surgery alone between 1994 and 2003. All resections were histopathologically radical. Follow-up was documented for at least 5 years. Fluorescence in situ hybridization (FISH) was used to examine all resection margins of all tumours for the presence of CI, which is indicated by the nuclear detection of chromosome imbalances and/or polyploidization for chromosomes 1 and 7. In addition, tissue sections were analysed for p53 expression by immunohistochemistry. Results Of the 25 patients, 11 developed a recurrence. FISH analysis showed that of the 11 recurrences, 8 exhibited CI in at least one resection margin. This relation was significant with a p -value of 0.011. There was a trend for p53 overexpression in the resection margins of tumours with recurrence, however, this trend was not statistically significant ( p = 0.082). Conclusion CI in the resection margins of OSCCs, even though histologically tumour-free, can reliably identify patients at risk for developing a local or locoregional recurrence. A future goal will be to investigate how radiotherapy following surgery influences the prognosis of these patients.

In four dimensions there are 4 different types of extremal Maxwell/scalar black holes characterized by a scalar coupling parameter $a$ with $a=0,1/\sqrt{3} , 1 , \sqrt{3}$. These black holes can be described as intersections of ten--dimensional non-singular Ramond-Ramond objects, i.e.~$D$-branes, waves and Taub-NUT solitons. Using this description it can be shown that the four--dimensional black holes decompactify near the core to higher--dimensional {\em non-singular} solutions. In terms of these higher--dimensional non-singular solutions we define a non-vanishing entropy for all four black hole types from a four--dimensional point of view.

The book starts with a nice historical introduction to the subject of zeta functions, zeta function regularization and its applications in physics. The author emphasizes some of the advantages of the zeta function regularization method. In particular, the zeta function regularization can conveniently be applied in a curved spacetime. Anybody who wants to get a quick overview of the state of the art in the zeta function regularization method is recommended to read this introduction. Apart from the introduction the main virtue of this book is to provide help to any physics student and/or researcher who encounters zeta functions in his/her work. For this purpose the book provides the reader first of all with many technical details about zeta functions and some of their most important properties. Crucial amongst these properties is the existence of the so-called zeta function regularization theorem. This theorem is discussed and explained in the first part of the book. At a more advanced level, the author emphasizes the importance of a non-trivial extension of the celebrated Chowla--Selberg formula. This extension was invented by the author and plays an important role in some of the physics applications discussed later in the book. The second and main part of the book is devoted to illustrate the zeta function regularization method by giving ten physical applications. These applications cover such a wide range of topics as the Casimir effect, Kaluza--Klein compactification, two- and three-dimensional quantum gravity, extended objects like strings and membranes, critical behaviour of a field theory at non-zero temperature and topological mass generation. It is needless to say that all these applications give an impressive overview of the universality and power of the zeta function regularization method. I like in particular the discussion of the Casimir effect which is done in quite some detail. Apart from the technical discussion the author also explains why the Casimir effect only received so much attention many years after its discovery. Finally, I should note that it is interesting that the book discusses an application to the theory of membranes and, more generally p-branes, which has received such renewed interest in the past year. In short, I can recommend this book to anybody who encounters zeta functions in research and/or education. Undoubtedly, this book will be of great help in taking away some of the confusion on this topic.