Paraoxonase gene polymorphisms and haplotype analysis in a stroke population

Peer reviewedPublisher PD

Strings in extremal BTZ black holes

We study the spectrum of the worldsheet theory of the bosonic closed string in the massless and extremal rotating BTZ black holes. We use a hyperbolic Wakimoto representation of the SL(2,R) currents to construct vertex operators for the string modes on these backgrounds. We argue that there are tachyons in the twisted sector, but these are not localised near the horizon. We study the relation to the null orbifold in the limit of vanishing cosmological constant. We also discuss the problem of extending this analysis to the supersymmetric case.Comment: 20 pages, no figure

Field cancerization in breast cancer

Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of the disease, often during its asymptomatic phase. Current practice in treatment and recurrence monitoring is based primarily on pathological evaluations but can also encompass genomic evaluations, both of which focus on the primary tumor. Although breast cancer is one of the most studied cancers, patients still recur at a rate of up to 15% within the first 10 years post‐surgery. Local recurrence was originally attributed to tumor cells contaminating histologically normal (HN) tissues beyond the surgical margin, but advances in technology have allowed for the identification of distinct aberrations that exist in the peri‐tumoral tissues themselves. One leading theory to explain this phenomenon is the field cancerization theory. Under this hypothesis, tumors arise from a field of molecularly altered cells that create a permissive environment for malignant evolution, which can occur with or without morphological changes. The traditional histopathology paradigm dictates that molecular alterations are reflected in the tissue phenotype. However, the spectrum of inter‐patient variability of normal breast tissue may obfuscate recognition of a cancerized field during routine diagnostics. In this review, we explore the concept of field cancerization focusing on HN peri‐tumoral tissues: we present the pathological and molecular features of field cancerization within these tissues and discuss how the use of peri‐tumoral tissues can affect research. Our observations suggest that pathological and molecular evaluations could be used synergistically to assess risk and guide the therapeutic management of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Bubbles Unbound: Bubbles of Nothing Without Kaluza-Klein

I present analytic time symmetric initial data for five dimensions describing ``bubbles of nothing'' which are asymptotically flat in the higher dimensional sense, i.e. there is no Kaluza-Klein circle asymptotically. The mass and size of these bubbles may be chosen arbitrarily and in particular the solutions contain bubbles of any size which are arbitrarily light. This suggests the solutions may be important phenomenologically and in particular I show that at low energy there are bubbles which expand outwards, suggesting a new possible instability in higher dimensions. Further, one may find bubbles of any size where the only region of high curvature is confined to an arbitrarily small volume.Comment: 27 pages, 2 figures, v2: minor changes, published versio

Longitudinal profiling of circulating tumour DNA for tracking tumour dynamics in pancreatic cancer.

BACKGROUND: The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. Here, we aimed to characterise and track patient-specific somatic ctDNA variants, to assess longitudinal changes in disease burden and explore the landscape of actionable alterations. METHODS: We followed 3 patients with resectable disease and 4 patients with unresectable disease, including 4 patients with ≥ 3 serial follow-up samples, of whom 2 were rare long survivors (> 5 years). We performed whole exome sequencing of tumour gDNA and plasma ctDNA (n = 20) collected over a ~ 2-year period from diagnosis through treatment to death or final follow-up. Plasma from 3 chronic pancreatitis cases was used as a comparison for analysis of ctDNA mutations. RESULTS: We detected > 55% concordance between somatic mutations in tumour tissues and matched serial plasma. Mutations in ctDNA were detected within known PDAC driver genes (KRAS, TP53, SMAD4, CDKN2A), in addition to patient-specific variants within alternative cancer drivers (NRAS, HRAS, MTOR, ERBB2, EGFR, PBRM1), with a trend towards higher overall mutation loads in advanced disease. ctDNA alterations with potential for therapeutic actionability were identified in all 7 patients, including DNA damage response (DDR) variants co-occurring with hypermutation signatures predictive of response to platinum chemotherapy. Longitudinal tracking in 4 patients with follow-up > 2 years demonstrated that ctDNA mutant allele fractions and clonal trends were consistent with CA19-9 measurements and/or clinically reported disease burden. The estimated prevalence of 'stem clones' was highest in an unresectable patient where changes in ctDNA dynamics preceded CA19-9 levels. Longitudinal evolutionary trajectories revealed ongoing subclonal evolution following chemotherapy. CONCLUSION: These results provide proof-of-concept for the use of exome sequencing of serial plasma to characterise patient-specific ctDNA profiles, and demonstrate the sensitivity of ctDNA in monitoring disease burden in PDAC even in unresectable cases without matched tumour genotyping. They reveal the value of tracking clonal evolution in serial ctDNA to monitor treatment response, establishing the potential of applied precision medicine to guide stratified care by identifying and evaluating actionable opportunities for intervention aimed at optimising patient outcomes for an otherwise intractable disease

Tachyon Condensation and Black Strings

We show that under certain conditions, closed string tachyon condensation produces a topology changing transition from black strings to Kaluza-Klein "bubbles of nothing." This can occur when the curvature at the horizon is much smaller than the string scale, so the black string is far from the correspondence point when it would make a transition to an excited fundamental string. This provides a dramatic new endpoint to Hawking evaporation. A similar transition occurs for black p-branes, and can be viewed as a nonextremal version of a geometric transition. Applications to AdS black holes and the AdS soliton are also discussed.Comment: 23 pages, 1 figure, v2: references adde

On fluctuations of closed string tachyon solitons

We discuss fluctuations on solitons in the dilaton/graviton/tachyon system using the low energy effective field theory approach. It is shown that closed string solitons are free of tachyons in this approximation, regardless of the exact shape of the tachyon potential.Comment: 13 pages, 1 figure, uses JHEP3.cl

Towards a Non-Relativistic Holographic Superfluid

We explore the phase structure of a holographic toy model of superfluid states in non-relativistic conformal field theories. At low background mass density, we find a familiar second-order transition to a superfluid phase at finite temperature. Increasing the chemical potential for the probe charge density drives this transition strongly first order as the low-temperature superfluid phase merges with a thermodynamically disfavored high-temperature condensed phase. At high background mass density, the system reenters the normal phase as the temperature is lowered further, hinting at a zero-temperature quantum phase transition as the background density is varied. Given the unusual thermodynamics of the background black hole, however, it seems likely that the true ground state is another configuration altogether.Comment: 13+5 pages, late

Closed string tachyons, flips and conifolds

Following the analysis of tachyons and orbifold flips described in hep-th/0412337, we study nonsupersymmetric analogs of the supersymmetric conifold singularity and show using their toric geometry description that they are nonsupersymmetric orbifolds of the latter. Using linear sigma models, we see that these are unstable to localized closed string tachyon condensation and exhibit flip transitions between their two small resolutions (involving 2-cycles), in the process mediating mild dynamical topology change. Our analysis shows that the structure of these nonsupersymmetric conifolds as quotients of the supersymmetric conifold obstructs the 3-cycle deformation of such singularities, suggesting that these nonsupersymmetric conifolds decay by evolving towards their stable small resolutions.Comment: Latex, 22 pgs, 2 figs. v4: matches JHEP version, 29 pgs, 3 figures, more elaborate Introduction, various clarifications adde