Long-term, treatment-free survival in select patients with distant metastatic papillary thyroid cancer

Well-differentiated thyroid carcinoma (WDTC) generally has a favorable prognosis. However, patients with distant metastatic disease experience progression of disease with a higher mortality. A subset of patients not previously described may challenge the conventional dogma regarding the progressive nature of all metastatic WDTC. Through analysis of our database, we identified patients with distant metastatic WDTC and persistent, minimally progressive disease. In all patients, persistent metastatic disease was confirmed via tissue biopsy, abnormal PET scan, and/or biochemical elevations in thyroglobulin or antibody levels. Progression of disease was monitored clinically and with repeat imaging. We describe five patients with WDTC and pulmonary metastases, aged 8–43 years at diagnosis. All patients underwent initial surgery and radioactive iodine (RAI) ablation, with some receiving multiple treatments. Persistent pulmonary metastatic disease was confirmed over decades (mean 22 years, range 8–42 years) with minimal progression despite no further treatment beyond thyroid hormone suppression. Persistent disease was biopsy-proven in all patients at a mean of 9.6 years from last RAI treatment. All patients had elevated thyroglobulin or anti-thyroglobulin antibody levels, while three demonstrated metabolically active disease with positive FDG uptake on PET scan, and one patient with persistent radioactive iodine avid pulmonary metastasis 36 years after her last RAI treatment. This case series demonstrates that some patients with distant metastases, even if metabolically active and radioactive iodine resistant, remain stable for decades without further treatment. Clinical awareness of such patients and continual reassessment of disease risk following initial therapy are crucial as aggressive treatment may not be necessary

Statistical mechanics of RNA folding: a lattice approach

We propose a lattice model for RNA based on a self-interacting two-tolerant trail. Self-avoidance and elements of tertiary structure are taken into account. We investigate a simple version of the model in which the native state of RNA consists of just one hairpin. Using exact arguments and Monte Carlo simulations we determine the phase diagram for this case. We show that the denaturation transition is first order and can either occur directly or through an intermediate molten phase.Comment: 8 pages, 9 figure

'Who do "they" cheer for?' Cricket, diaspora, hybridity and divided loyalties amongst British Asians

This article explores the relationship between British Asians' sense of nationhood, citizenship, ethnicity and some of their manifestations in relation to sports fandom: specifically in terms of how cricket is used as a means of articulating diasporic British Asian identities. Norman Tebbit's 'cricket test' is at the forefront of this article to tease out the complexities of being British Asian in terms of supporting the English national cricket team. The first part of the article locates Tebbit's 'cricket test' within the wider discourse of multiculturalism. The analysis then moves to focus on the discourse of sports fandom and the concept of 'home team advantage' arguing that sports venues represent significant sites for nationalist and cultural expression due to their connection with national history. The article highlights how supporting 'Anyone but England', thereby rejecting ethnically exclusive notions of 'Englishness' and 'Britishness', continues to be a definer of British Asians' cultural identities. The final section situates these trends within the discourse of hybridity and argues that sporting allegiances are often separate from considerations of national identity and citizenship. Rather than placing British Asians in an either/or situation, viewing British 'Asianness' in hybrid terms enables them to celebrate their traditions and histories, whilst also being proud of their British citizenship. © The Author(s) 2011

The making of English cricket cultures: Empire, globalization and (post) colonialism

The aim of this article is to understand how English cricket cultures have been made, negotiated and, ultimately, resisted in the context of (post) colonialism. I draw upon research undertaken with white and British Asian cricketers in Yorkshire to identify the place and significance of cricket within the everyday lives of British Asian communities. Over the last decade the number of British Asian cricketers progressing into the upper echelons of the game (mainly the English County Championship) has increased. Many within the game (mainly white people) have used these figures to argue that English cricket is now 'colour blind'. However, I argue that representation is not the equivalent to acceptance and integration, and present evidence to suggest that racial prejudice and discrimination, not to mention inaccurate and essentialized cultural stereotypes of British Asian cricketers, remain firmly and routinely embedded in aspects of the sport at all levels. I argue that the ability of British Asians to resist the hegemonic structures of white 'Englishness', by asserting their own distinctive post-colonial identities in cricket, is paramount to their everyday negotiations of power and racism. © 2011 Taylor & Francis

Two-Dimensional Polymers with Random Short-Range Interactions

We use complete enumeration and Monte Carlo techniques to study two-dimensional self-avoiding polymer chains with quenched ``charges'' $\pm 1$. The interaction of charges at neighboring lattice sites is described by $q_i q_j$. We find that a polymer undergoes a collapse transition at a temperature $T_{\theta}$, which decreases with increasing imbalance between charges. At the transition point, the dependence of the radius of gyration of the polymer on the number of monomers is characterized by an exponent $\nu_{\theta} = 0.60 \pm 0.02$, which is slightly larger than the similar exponent for homopolymers. We find no evidence of freezing at low temperatures.Comment: 4 two-column pages, 6 eps figures, RevTex, Submitted to Phys. Rev.

Structural Dynamic of a Self-Assembling Peptide d-EAK16 Made of Only D-Amino Acids

We here report systematic study of structural dynamics of a 16-residue self-assembling peptide d-EAK16 made of only D-amino acids. We compare these results with its chiral counterpart L-form, l-EAK16. Circular dichroism was used to follow the structural dynamics under various temperature and pH conditions. At 25°C the d-EAK16 peptide displayed a typical beta-sheet spectrum. Upon increasing the temperature above 70°C, there was a spectrum shift as the 218 nm valley widens toward 210 nm. Above 80°C, the d-EAK16 peptide transformed into a typical alpha-helix CD spectrum without going through a detectable random-coil intermediate. When increasing the temperature from 4°C to 110°C then cooling back from 110°C to 4°C, there was a hysteresis: the secondary structure from beta-sheet to alpha-helix and then from alpha-helix to beta-sheet occurred. d-EAK16 formed an alpha-helical conformation at pH0.76 and pH12 but formed a beta-sheet at neutral pH. The effects of various pH conditions, ionic strength and denaturing agents were also noted. Since D-form peptides are resistant to natural enzyme degradation, such drastic structural changes may be exploited for fabricating molecular sensors to detect minute environmental changes. This provides insight into the behaviors of self-assembling peptides made of D-amino acids and points the way to designing new peptide materials for biomedical engineering and nanobiotechnology

Representations of sport in the revolutionary socialist press in Britain, 1988–2012

This paper considers how sport presents a dualism to those on the far left of the political spectrum. A long-standing, passionate debate has existed on the contradictory role played by sport, polarised between those who reject it as a bourgeois capitalist plague and those who argue for its reclamation and reformation. A case study is offered of a political party that has consistently used revolutionary Marxism as the basis for its activity and how this party, the largest in Britain, addresses sport in its publications. The study draws on empirical data to illustrate this debate by reporting findings from three socialist publications. When sport did feature it was often in relation to high profile sporting events with a critical tone adopted and typically focused on issues of commodification, exploitation and alienation of athletes and supporters. However, readers’ letters, printed in the same publications, revealed how this interpretation was not universally accepted, thus illustrating the contradictory nature of sport for those on the far left

Decay of isolated surface features driven by the Gibbs-Thomson effect in analytic model and simulation

A theory based on the thermodynamic Gibbs-Thomson relation is presented which provides the framework for understanding the time evolution of isolated nanoscale features (i.e., islands and pits) on surfaces. Two limiting cases are predicted, in which either diffusion or interface transfer is the limiting process. These cases correspond to similar regimes considered in previous works addressing the Ostwald ripening of ensembles of features. A third possible limiting case is noted for the special geometry of "stacked" islands. In these limiting cases, isolated features are predicted to decay in size with a power law scaling in time: A is proportional to (t0-t)^n, where A is the area of the feature, t0 is the time at which the feature disappears, and n=2/3 or 1. The constant of proportionality is related to parameters describing both the kinetic and equilibrium properties of the surface. A continuous time Monte Carlo simulation is used to test the application of this theory to generic surfaces with atomic scale features. A new method is described to obtain macroscopic kinetic parameters describing interfaces in such simulations. Simulation and analytic theory are compared directly, using measurements of the simulation to determine the constants of the analytic theory. Agreement between the two is very good over a range of surface parameters, suggesting that the analytic theory properly captures the necessary physics. It is anticipated that the simulation will be useful in modeling complex surface geometries often seen in experiments on physical surfaces, for which application of the analytic model is not straightforward.Comment: RevTeX (with .bbl file), 25 pages, 7 figures from 9 Postscript files embedded using epsf. Submitted to Phys. Rev. B A few minor changes made on 9/24/9

Characterization of an engineered human purine nucleoside phosphorylase fused to an anti-her2/neu single chain Fv for use in ADEPT

Abstract Background Antibody Directed Enzyme Prodrug Therapy (ADEPT) can be used to generate cytotoxic agents at the tumor site. To date non-human enzymes have mainly been utilized in ADEPT. However, these non-human enzymes are immunogenic limiting the number of times that ADEPT can be administered. To overcome the problem of immunogenicity, a fully human enzyme, capable of converting a non-toxic prodrug to cytotoxic drug was developed and joined to a human tumor specific scFv yielding a fully human targeting agent. Methods A double mutant of human purine nucleoside phosphorylase (hDM) was developed which unlike the human enzyme can cleave adenosine-based prodrugs. For tumor-specific targeting, hDM was fused to the human anti-HER2/neu single chain Fv (scFv), C6 MH3B1. Enzymatic activity of hDM with its natural substrates and prodrugs was determined using spectrophotomeric approaches. A cell proliferation assay was used to assess the cytotoxicity generated following conversion of prodrug to drug as a result of enzymatic activity of hDM. Affinity of the targeting scFv, C6 MH3B1 fused to hDM to Her2/neu was confirmed using affinity chromatography, surface plasmon resonance, and flow-cytometry. Results In vitro hDM-C6 MH3B1 binds specifically to HER2/neu expressing tumor cells and localizes hDM to tumor cells, where the enzymatic activity of hDM-C6 MH3B1, but not the wild type enzyme, results in phosphorolysis of the prodrug, 2-fluoro-2'-deoxyadenosine to the cytotoxic drug 2-fluoroadenine (F-Ade) causing inhibition of tumor cell proliferation. Significantly, the toxic small drug diffuses through the cell membrane of HER2/neu expressing cells as well as cells that lack the expression of HER2/neu, causing a bystander effect. F-Ade is toxic to cells irrespective of their growth rate; therefore, both the slowly dividing tumor cells and the non-dividing neighboring stromal cells that support tumor growth should be killed. Analysis of potential novel MHCII binding peptides resulting from fusion of hDM to C6 MH3B1 and the two mutations in hDM, and of the structure of hDM compared to the wild-type enzyme suggests that hDM-C6 MH3B1 should exhibit minimal immunogenicity in humans. Conclusion hDM-C6 MH3B1 constitutes a novel human based protein that addresses some of the limitations of ADEPT that currently preclude its successful use in the clinic