Determinants of outcome following surgery for oral squamous cell carcinoma

The recent changes in incidence and prevalence of oral squamous cell carcinoma in relation to gender and age mirror the changing patterns of exposure to tobacco and alcohol, the main etiological agents. Most cases of oral cancer are managed by surgery, often combined with radiotherapy. Histopathological assessment of the resection specimen provides information vital for postoperative management and prognosis. This review considers the full range of histological determinants of outcome in relation to the primary oral tumor and any metastatic involvement of the cervical lymphatic system, together with an outline of more general patient factors that may also impact on morbidity and mortality rates. </jats:p

CpG island methylation phenotype (CIMP) in oral cancer: associated with a marked inflammatory response and less aggressive tumour biology.

Studies in several tumour sites highlight the significance of the CpG island methylation phenotype (CIMP), with distinct features of histology, biological aggression and outcome. We utilise pyrosequencing techniques of quantitative methylation analysis to investigate the presence of CIMP in oral squamous cell carcinoma (OSCC) for the first time, and evaluate its correlation with allelic imbalance, pathology and clinical behaviour. Tumour tissue, control tissue and PBLs were obtained from 74 patients with oral squamous cell carcinoma. Pyrosequencing was used to analyse methylation patterns in 75-200 bp regions of the CpG rich gene promoters of 10 genes with a broad range of cellular functions. Allelic imbalance was investigated using a multiplexed panel of 11 microsatellite markers. Corresponding variables, histopathological staging and grading were correlated with these genetic and epigenetic aberrations. A cluster of tumours with a greater degree of promoter methylation than would be predicted by chance alone (P=0.001) were designated CIMP+ve. This group had less aggressive tumour biology in terms of tumour thickness (p=0.015) and nodal metastasis (P=0.012), this being apparently independent of tumour diameter. Further, it seems that these CIMP+ve tumours excited a greater host inflammatory response (P=0.019). The exact mechanisms underlying CIMP remain obscure but the association with a greater inflammatory host response supports existing theories relating these features in other tumour sites. As CIMP has significant associations with other well documented prognostic indicators, it may prove beneficial to include methylation analyses in molecular risk modelling of tumours

Performing the responsive and committed employee through the sociomaterial mangle of connection

In the light of increasingly mobile and flexible work, maintaining connections to work is presented as vital. Various studies have sought to understand how these connections are experienced and managed, particularly through the use of smartphones (e.g. Mazmanian, Orlikowski & Yates, 2013). We take a new perspective on this practice by bringing together the conceptual fields of sociomateriality (Pickering, 1995) and identity work (Svenningsson & Alvesson, 2003). Through the analysis of narratives produced by smartphone users in an engineering firm we argue that connection can be viewed as a sociomaterial assemblage that performs particular identities: being contactable and responsive; being involved and committed; and being in-demand and authoritative. Through this analysis we both elaborate the concept of connectivity at work and indicate how the material is implicated in identity performances

Improving the delivery of care for patients with diabetes through understanding optimised team work and organisation in primary care

Peer reviewedPublisher PD

A Lyman-alpha-only AGN from the Sloan Digital Sky Survey

The Sloan Digital Sky Survey has discovered a z=2.4917 radio-loud active galactic nucleus (AGN) with a luminous, variable, low-polarization UV continuum, H I two-photon emission, and a moderately broad Lyman-alpha line (FWHM = 1430 km/s) but without obvious metal-line emission. SDSS J113658.36+024220.1 does have associated metal-line absorption in three distinct, narrow systems spanning a velocity range of 2710 km/s. Despite certain spectral similarities, SDSS J1136+0242 is not a Lyman-break galaxy. Instead, the Ly-alpha and two-photon emission can be attributed to an extended, low-metallicity narrow-line region. The unpolarized continuum argues that we see SDSS J1136+0242 very close to the axis of any ionization cone present. We can conceive of two plausible explanations for why we see a strong UV continuum but no broad-line emission in this `face-on radio galaxy' model for SDSS J1136+0242: the continuum could be relativistically beamed synchrotron emission which swamps the broad-line emission; or, more likely, SDSS J1136+0242 could be similar to PG 1407+265, a quasar in which for some unknown reason the high-ionization emission lines are very broad, very weak, and highly blueshifted.Comment: AJ, in press, 10 pages emulateapj forma

Optical and Radio Properties of Extragalactic Sources Observed by the FIRST and SDSS Surveys

We discuss the optical and radio properties of 30,000 FIRST sources positionally associated with an SDSS source in 1230 deg$^2$ of sky. The majority (83%) of the FIRST sources identified with an SDSS source brighter than r=21 are optically resolved. We estimate an upper limit of 5% for the fraction of quasars with broad-band optical colors indistinguishable from those of stars. The distribution of quasars in the radio flux -- optical flux plane supports the existence of the "quasar radio-dichotomy"; 8% of all quasars with i<18.5 are radio-loud and this fraction seems independent of redshift and optical luminosity. The radio-loud quasars have a redder median color by 0.08 mag, and a 3 times larger fraction of objects with red colors. FIRST galaxies represent 5% of all SDSS galaxies with r<17.5, and 1% for r<20, and are dominated by red galaxies. Magnitude and redshift limited samples show that radio galaxies have a different optical luminosity distribution than non-radio galaxies selected by the same criteria; when galaxies are further separated by their colors, this result remains valid for both blue and red galaxies. The distributions of radio-to-optical flux ratio are similar for blue and red galaxies in redshift-limited samples; this similarity implies that the difference in their luminosity functions, and resulting selection effects, are the dominant cause for the preponderance of red radio galaxies in flux-limited samples. We confirm that the AGN-to-starburst galaxy number ratio increases with radio flux, and find that radio emission from AGNs is more concentrated than radio emission from starburst galaxies (abridged).Comment: submitted to AJ, color gif figures, PS figures available from [email protected]

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define