Clinical and Molecular Determinants of Malignant Transformation in Oral Epithelial Dysplasia

Known risk factors for malignant transformation in oral lesions with malignant potential include the size and appearance, however the importance of site, grade of dysplasia and exposure to environmental carcinogens remains controversial. Patients with a diagnosis of oral epithelial dysplasia (OED) were recruited to a longitudinal observational cohort study in a tertiary oral dysplasia clinic. Clinical, histopathological and risk factor data were assessed to identify clinical determinants of malignant transformation; in patients where the oral dysplasia underwent malignant transformation the treatment outcomes were evaluated. Ninety-eight eligible patients were recruited and followed up for the median duration of 48 months. Twenty-six (26.5%) patients underwent malignant transformation, with significant predictors as follows: non-smoking status, lateral tongue subsite, non-homogeneous appearance, high histological grade and size of lesion >200mm2. Whilst these clinical features have previously been associated with malignant transformation in OED, the highly statistically significant finding of malignant transformation in non-smokers, consistent with several cohorts reported in the recent years. This suggests that these patients, apparently with endogenous OED, perhaps with inherited or acquired predisposition, are considered to be at higher risk (compared to smokers) and should form the focus for further investigation. All 26 patients in whom dysplasia transformed to oral squamous cell carcinoma were presented to the multidisciplinary team (MDT) with stage 1 disease. Ninety-one percent (21/23) were initially treated by wide local excision and 9% (2/23) required tumour resection followed by reconstruction. Twenty-two percent (5/23) of patients developed second primary OSCC, and further diagnoses of oral dysplasia with an estimate that 76% of patients will undergo one or more event in 5 years. Specialist monitoring of OED by a multidisciplinary team allows detection of OSCC at an early stage, facilitating largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary OSCC formation in high risk patients with OED supports an intensive targeted surveillance regimen in this group of patients. The observed higher rate of malignant transformation in non (or light)-smokers supports the hypothesis of an endogenous aetiology. It is hypothesised that loss of FANCD2 and associated proteins lead to genomic instability and oncogenesis. Longitudinal archival samples were obtained from 40 individuals with OED from time of diagnosis to the most recent clinical review in 23 non-transforming/stable OED or until excision of the SCC in 17 unstable OED undergoing malignant transformation. Histopathological reassessment, immunohistochemistry for FANCD2 and Western blotting for phosphorylation/mono-ubiquitination status of ATR, CHK1, FANCD2 and FANCG were undertaken on each tissue sample. Immunohistochemistry studies found under-expression of FANCD2 was observed in the diagnostic biopsy of OED lesions which later underwent malignant transformation when compared with stable OED. Combining the FANCD2 immunohistochemistry scores with histological grading more accurately predicted malignant transformation (p=0.005) than histology alone and correctly predicted malignant transformation in 10/17 initial biopsies. A significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1 and pFANCG were observed in OED which underwent malignant transformation. There is strong evidence that defects in the DNA damage sensing-signalling-repair cascade are associated with malignant transformation in OED. Loss of post-translational modification in FANCD2 and related proteins, was more predictive of malignant transformation when compared to clinical parameters

Direct Observation of the Superfluid Phase Transition in Ultracold Fermi Gases

Water freezes into ice, atomic spins spontaneously align in a magnet, liquid helium becomes superfluid: Phase transitions are dramatic phenomena. However, despite the drastic change in the system's behaviour, observing the transition can sometimes be subtle. The hallmark of Bose-Einstein condensation (BEC) and superfluidity in trapped, weakly interacting Bose gases is the sudden appearance of a dense central core inside a thermal cloud. In strongly interacting gases, such as the recently observed fermionic superfluids, this clear separation between the superfluid and the normal parts of the cloud is no longer given. Condensates of fermion pairs could be detected only using magnetic field sweeps into the weakly interacting regime. The quantitative description of these sweeps presents a major theoretical challenge. Here we demonstrate that the superfluid phase transition can be directly observed by sudden changes in the shape of the clouds, in complete analogy to the case of weakly interacting Bose gases. By preparing unequal mixtures of the two spin components involved in the pairing, we greatly enhance the contrast between the superfluid core and the normal component. Furthermore, the non-interacting wings of excess atoms serve as a direct and reliable thermometer. Even in the normal state, strong interactions significantly deform the density profile of the majority spin component. We show that it is these interactions which drive the normal-to-superfluid transition at the critical population imbalance of 70(5)%.Comment: 16 pages (incl. Supplemental Material), 5 figure

Refining the indications for scapula tip in mandibular reconstruction

Mandibular reconstruction in osteoradionecrosis or salvage surgery can often be complicated by the lack of suitable recipient vessels in the ipsilateral neck and the associated requirement for significant extraoral skin reconstruction. The scapula tip with its long vascular pedicle and option of a chimeric soft tissue component offers a versatile reconstructive solution in such cases. This article reports four consecutive cases of mandibular reconstruction with poor ipsilateral vascular options and additional soft tissue requirements in which the scapula tip was justified and preferred. The blood supply to the lateral scapula through the circumflex scapular system is well established in the literature and this would be the preferred reconstruction in class I mandibular defects associated with a significant soft tissue requirement. The scapula tip would suit cases where the ipsilateral recipient vessels are compromised, and so justify the potential for mandibular reconstruction with inferior bone stock

Using Bars As Signposts of Galaxy Evolution at High and Low Redshifts

An analysis of the NICMOS Deep Field shows that there is no evidence of a decline in the bar fraction beyond z~0.7, as previously claimed; both bandshifting and spatial resolution must be taken into account when evaluating the evolution of the bar fraction. Two main caveats of this study were a lack of a proper comparison sample at low redshifts and a larger number of galaxies at high redshifts. We address these caveats using two new studies. For a proper local sample, we have analyzed 134 spirals in the near-infrared using 2MASS (main results presented by Menendez-Delmestre in this volume) which serves as an ideal anchor for the low-redshift Universe. In addition to measuring the mean bar properties, we find that bar size is correlated with galaxy size and brightness, but the bar ellipticity is not correlated with these galaxy properties. The bar length is not correlated with the bar ellipticity. For larger high redshift samples we analyze the bar fraction from the 2-square degree COSMOS ACS survey. We find that the bar fraction at z~0.7 is ~50%, consistent with our earlier finding of no decline in bar fraction at high redshifts.Comment: In the proceedings of "Penetrating Bars through Masks of Cosmic Dust: The Hubble Tuning Fork strikes a New Note

A parabolic approach to the control of opinion spreading

We analyze the problem of controlling to consensus a nonlinear system modeling opinion spreading. We derive explicit exponential estimates on the cost of approximately controlling these systems to consensus, as a function of the number of agents N and the control time-horizon T. Our strategy makes use of known results on the controllability of spatially discretized semilinear parabolic equations. Both systems can be linked through time-rescalin

A quantitative account of genomic island acquisitions in prokaryotes

<p>Abstract</p> <p>Background</p> <p>Microbial genomes do not merely evolve through the slow accumulation of mutations, but also, and often more dramatically, by taking up new DNA in a process called horizontal gene transfer. These innovation leaps in the acquisition of new traits can take place via the introgression of single genes, but also through the acquisition of large gene clusters, which are termed Genomic Islands. Since only a small proportion of all the DNA diversity has been sequenced, it can be hard to find the appropriate donors for acquired genes via sequence alignments from databases. In contrast, relative oligonucleotide frequencies represent a remarkably stable genomic signature in prokaryotes, which facilitates compositional comparisons as an alignment-free alternative for phylogenetic relatedness.</p> <p>In this project, we test whether Genomic Islands identified in individual bacterial genomes have a similar genomic signature, in terms of relative dinucleotide frequencies, and can therefore be expected to originate from a common donor species.</p> <p>Results</p> <p>When multiple Genomic Islands are present within a single genome, we find that up to 28% of these are compositionally very similar to each other, indicative of frequent recurring acquisitions from the same donor to the same acceptor.</p> <p>Conclusions</p> <p>This represents the first quantitative assessment of common directional transfer events in prokaryotic evolutionary history. We suggest that many of the resident Genomic Islands per prokaryotic genome originated from the same source, which may have implications with respect to their regulatory interactions, and for the elucidation of the common origins of these acquired gene clusters.</p