Verrucous carcinoma (carcinoma cuniculatum) of the head and neck: what do we know now that we did not know a decade ago?

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Optimal Location of Sources in Transportation Networks

We consider the problem of optimizing the locations of source nodes in transportation networks. A reduction of the fraction of surplus nodes induces a glassy transition. In contrast to most constraint satisfaction problems involving discrete variables, our problem involves continuous variables which lead to cavity fields in the form of functions. The one-step replica symmetry breaking (1RSB) solution involves solving a stable distribution of functionals, which is in general infeasible. In this paper, we obtain small closed sets of functional cavity fields and demonstrate how functional recursions are converted to simple recursions of probabilities, which make the 1RSB solution feasible. The physical results in the replica symmetric (RS) and the 1RSB frameworks are thus derived and the stability of the RS and 1RSB solutions are examined.Comment: 38 pages, 18 figure

Discrete embedded solitons

We address the existence and properties of discrete embedded solitons (ESs), i.e., localized waves existing inside the phonon band in a nonlinear dynamical-lattice model. The model describes a one-dimensional array of optical waveguides with both the quadratic (second-harmonic generation) and cubic nonlinearities. A rich family of ESs was previously known in the continuum limit of the model. First, a simple motivating problem is considered, in which the cubic nonlinearity acts in a single waveguide. An explicit solution is constructed asymptotically in the large-wavenumber limit. The general problem is then shown to be equivalent to the existence of a homoclinic orbit in a four-dimensional reversible map. From properties of such maps, it is shown that (unlike ordinary gap solitons), discrete ESs have the same codimension as their continuum counterparts. A specific numerical method is developed to compute homoclinic solutions of the map, that are symmetric under a specific reversing transformation. Existence is then studied in the full parameter space of the problem. Numerical results agree with the asymptotic results in the appropriate limit and suggest that the discrete ESs may be semi-stable as in the continuous case.Comment: A revtex4 text file and 51 eps figure files. To appear in Nonlinearit

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Current Treatment of Endolymphatic Sac Tumor of the Temporal Bone

An endolymphatic sac tumor (ELST) is a rare, indolent but locally aggressive tumor arising in the posterior petrous ridge. Patients present with sensorineural hearing loss and tinnitus. As the tumor progresses, patients may experience vertigo, ataxia, facial nerve paresis, pain and otorrhea. Most patients present in their 4th or 5th decade with a wide age range. Patients with von Hippel–Lindau disease have an increased likelihood of developing ELST. Histologically, ELST is a low-grade adenocarcinoma. As it progresses, it destroys bone and extends into adjacent tissues. The likelihood of regional or distant metastases is remote. The optimal treatment is resection with negative margins. Patients with positive margins, gross residual disease, or unresectable tumor are treated with radiotherapy or radiosurgery. Late recurrences are common, so long follow-up is necessary to assess efficacy. The likelihood of cure depends on tumor extent and is probably in the range of 50–75%

Downregulation of the Hsp90 System Causes Defects in Muscle Cells of Caenorhabditis Elegans

The ATP-dependent molecular chaperone Hsp90 is required for the activation of a variety of client proteins involved in various cellular processes. Despite the abundance of known client proteins, functions of Hsp90 in the organismal context are not fully explored. In Caenorhabditis elegans, Hsp90 (DAF-21) has been implicated in the regulation of the stress-resistant dauer state, in chemosensing and in gonad formation. In a C. elegans strain carrying a DAF-21 mutation with a lower ATP turnover, we observed motility defects. Similarly, a reduction of DAF-21 levels in wild type nematodes leads to reduced motility and induction of the muscular stress response. Furthermore, aggregates of the myosin MYO-3 are visible in muscle cells, if DAF-21 is depleted, implying a role of Hsp90 in the maintenance of muscle cell functionality. Similar defects can also be observed upon knockdown of the Hsp90-cochaperone UNC-45. In life nematodes YFP-DAF-21 localizes to the I-band and the M-line of the muscular ultrastructure, but the protein is not stably attached there. The Hsp90-cofactor UNC-45-CFP contrarily can be found in all bands of the nematode muscle ultrastructure and stably associates with the UNC-54 containing A-band. Thus, despite the physical interaction between DAF-21 and UNC-45, apparently the two proteins are not always localized to the same muscular structures. While UNC-45 can stably bind to myofilaments in the muscular ultrastructure, Hsp90 (DAF-21) appears to participate in the maintenance of muscle structures as a transiently associated diffusible factor

Cervical lymph node metastasis in high-grade transformation of head and neck adenoid cystic carcinoma: a collective international review

Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation

Fatou’s Associates

Suppose that f is a transcendental entire function, V⊊C is a simply connected domain, and U is a connected component of f-1(V). Using Riemann maps, we associate the map f : U→V to an inner function g : D→D. It is straightforward to see that g is either a finite Blaschke product, or, with an appropriate normalisation, can be taken to be an infinite Blaschke product. We show that when the singular values of f in V lie away from the boundary, there is a strong relationship between singularities of g and accesses to infinity in U. In the case where U is a forward-invariant Fatou component of f, this leads to a very significant generalisation of earlier results on the number of singularities of the map g. If U is a forward-invariant Fatou component of f there are currently very few examples where the relationship between the pair (f, U) and the function g has been calculated. We study this relationship for several well-known families of transcendental entire functions. It is also natural to ask which finite Blaschke products can arise in this manner, and we show the following: for every finite Blaschke product g whose Julia set coincides with the unit circle, there exists a transcendental entire function f with an invariant Fatou component such that g is associated with f in the above sense. Furthermore, there exists a single transcendental entire function f with the property that any finite Blaschke product can be arbitrarily closely approximated by an inner function associated with the restriction of f to a wandering domain