A Generalization of Quantum Statistics

We propose a new fractional statistics for arbitrary dimensions, based on an extension of Pauli's exclusion principle, to allow for finite multi-occupancies of a single quantum state. By explicitly constructing the many-body Hilbert space, we obtain a new algebra of operators and a new thermodynamics. The new statistics is different from fractional exclusion statistics; and in a certain limit, it reduces to the case of parafermi statistics.Comment: 11 pages, late

Anomalous particle-production thresholds through systematic and non-systematic quantum-gravity effects

A growing number of studies is being devoted to the identification of plausible quantum properties of spacetime which might give rise to observably large effects. The literature on this subject is now relatively large, including studies in string theory, loop quantum gravity and noncommutative geometry. It is useful to divide the various proposals into proposals involving a systematic quantum-gravity effect (an effect that would shift the main/average prediction for a given observable quantity) and proposals involving a non-systematic quantum-gravity effect (an effect that would introduce new fundamental uncertanties in some observable quantity). The case of quantum-gravity-induced particle-production-threshold anomalies, a much studied example of potentially observable quantum-gravity effect, is here used as an example to illustrate the differences to be expected between systematic and non-systematic effects.Comment: 10 pages, LaTe

A GENERALIZATION OF QUANTUM STATISTICS

We propose a new fractional statistics for arbitrary dimensions, based on an extension of Pauli’s exclusion principle, to allow for finite multi-occupancies of a single quantum state. By explicitly constructing the many-body Hilbert space, we obtain a new algebra of operators and a new thermodynamics. The new statistics is different from fractional exclusion statistics; and in a certain limit, it reduces to the case of parafermi statistics

Prognostic factors and patterns of recurrence in esophageal cancer assert arguments for extended two-field transthoracic esophagectomy

BACKGROUND: High recurrence rates determine the dismal outcome in esophageal cancer. We reviewed our experiences and defined prognostic factors and patterns of recurrences after curatively, intended transthoracic esophagectomy. METHODS: Between January 1991 and December 2005, 212 consecutive patients underwent a radical transthoracic esophagectomy with extended 2-field lymphadenectomy. Recurrence rates, survival, and prognostic factors were analyzed (minimal follow-up period, 2 y). RESULTS: Radicality was obtained in 85.6%. The median follow-up period was 26.6 months. The overall recurrence rate at I, 3, and 5 years was 28%, 44%, and 64%, respectively, and locoregional recurrence rate was 17%, 27%, and 43%, respectively. Overall survival rates, including postoperative deaths, were 45% and 34% at 3 and 5 years, respectively. pT stage and lymph node (LN) ratio greater than .20 were independent prognostic factors for survival and recurrences. Radicality was most prognostic for survival, and for N+ greater than 4 positive LN for recurrences. CONCLUSIONS: Radicality and LN ratio are strong prognostic factors. High radicality and adequate nodal assessment are guaranteed by an extended transthoracic approach. (C) 2010 Elsevier Inc. All rights reserved

A Critical Appraisal of Circumferential Resection Margins in Esophageal Carcinoma

In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the optimal limit of CRM.To define the optimal tumor-free CRM we included 98 consecutive patients who underwent extended esophagectomy with microscopic tumor-free resection margins (R0) between 1997 and 2006. CRMs were measured in tenths of millimeters with inked lateral margins. Outcome of patients with CRM involvement was compared with a statistically comparable control group of 21 patients with microscopic positive resection margins (R1).A cutoff point of CRM at a parts per thousand currency sign1.0 mm and &gt; 1.0 mm appeared to be an adequate marker for survival and prognosis (both P &lt;0.001). The outcome in patients with CRMs a parts per thousand currency sign1.0 and &gt; 0 mm was equal to that in patients with CRM of 0 mm (P = 0.43). CRM involvement was an independent prognostic factor for both recurrent disease (P = 0.001) and survival (P &lt;0.001). Survival of patients with positive CRMs (a parts per thousand currency sign1 mm) did not significantly differ from patients with an R1 resection (P = 0.12).Involvement of the circumferential resection margins is an independent prognostic factor for recurrent disease and survival in esophageal cancer. The optimal limit for a positive CRM is a parts per thousand currency sign1 mm and for a free CRM is &gt; 1.0 mm. Patients with unfavorable CRM should be approached as patients with R1 resection with corresponding outcome.</p

A Standardized Framework for Fluorescence-Guided Margin Assessment for Head and Neck Cancer Using a Tumor Acidosis Sensitive Optical Imaging Agent

PURPOSE: Intra-operative management of the surgical margin in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) remains challenging as surgeons still have to rely on visual and tactile information. Fluorescence-guided surgery using tumor-specific imaging agents can assist in clinical decision-making. However, a standardized imaging methodology is lacking. In this study, we determined whether a standardized, specimen-driven, fluorescence imaging framework using ONM-100 could assist in clinical decision-making during surgery. PROCEDURES: Thirteen patients with histologically proven HNSCC were included in this clinical study and received ONM-100 24 ± 8 h before surgery. Fluorescence images of the excised surgical specimen and of the surgical cavity were analyzed. A fluorescent lesion with a tumor-to-background ratio (TBR) > 1.5 was considered fluorescence-positive and correlated to standard of care (SOC) histopathology. RESULTS: All six tumor-positive surgical margins were detected immediately after excision using fluorescence-guided intra-operative imaging. Postoperative analysis showed a median TBR (±IQR) of the fluorescent lesions on the resection margin of 3.36 ± 1.62. Three fluorescence-positive lesions in the surgical cavity were biopsied and showed occult carcinoma and severe dysplasia, and a false-positive fluorescence lesion. CONCLUSION: Our specimen-driven fluorescence framework using a novel, pH-activatable, fluorescent imaging agent could assist in reliable and real-time adequate clinical decision-making showing that a fluorescent lesion on the surgical specimen with a TBR of 1.5 is correlated to a tumor-positive resection margin. The binary mechanism of ONM-100 allows for a sharp tumor delineation in all patients, giving the surgeon a clinical tool for real-time margin assessment, with a high sensitivity

Implications of Spacetime Quantization for the Bahcall-Waxman Neutrino Bound

There is growing interest in quantum-spacetime models in which small departures from Lorentz symmetry are governed by the Planck scale. In particular, several studies have considered the possibility that these small violations of Lorentz symmetry may affect various astrophysical observations, such as the evaluation of the GZK limit for cosmic rays, the interaction of TeV photons with the Far Infrared Background and the arrival time of photons with different energies from cosmological sources. We show that the same Planck-scale departures from Lorentz symmetry that lead to a modification of the GZK limit which would be consistent with the observations reported by AGASA, also have significant implications for the evaluation of the Bahcall-Waxman bound on the flux of high-energy neutrinos produced by photo-meson interactions in sources of size not much larger than the proton photo-meson mean free path.Comment: 10 pages, Late

Survival of patients with colorectal liver metastases treated with and without preoperative chemotherapy:Nationwide propensity score-matched study

Introduction: Routine treatment with preoperative systemic chemotherapy (CTx) in patients with colorectal liver metastases (CRLM) remains controversial due to lack of consistent evidence demonstrating associated survival benefits. This study aimed to determine the effect of preoperative CTx on overall survival (OS) compared to surgery alone and to assess hospital and oncological network variation in 5-year OS. Methods: This was a population-based study of all patients who underwent liver resection for CRLM between 2014 and 2017 in the Netherlands. After 1:1 propensity score matching (PSM), OS was compared between patients treated with and without preoperative CTx. Hospital and oncological network variation in 5-year OS corrected for case-mix factors was calculated using an observed/expected ratio. Results: Of 2820 patients included, 852 (30.2%) and 1968 (69.8%) patients were treated with preoperative CTx and surgery alone, respectively. After PSM, 537 patients remained in each group, median number of CRLM; 3 [IQR 2–4], median size of CRLM; 28 mm [IQR 18–44], synchronous CLRM (71.1%). Median follow-up was 80.8 months. Five-year OS rates after PSM for patients treated with and without preoperative chemotherapy were 40.2% versus 38.3% (log-rank P = 0.734). After stratification for low, medium, and high tumour burden based on the tumour burden score (TBS) OS was similar for preoperative chemotherapy vs. surgery alone (log-rank P = 0.486, P = 0.914, and P = 0.744, respectively). After correction for non-modifiable patient and tumour characteristics, no relevant hospital or oncological network variation in five-year OS was observed. Conclusion: In patients eligible for surgical resection, preoperative chemotherapy does not provide an overall survival benefit compared to surgery alone.</p

Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW:A quantitative dose-escalation study

Tumor-positive resection margins are present in up to 23% of head and neck cancer (HNC) surgeries, as intraoperative techniques for real-time evaluation of the resection margins are lacking. In this study, we investigated the safety and potential clinical value of fluorescence-guided imaging (FGI) for resection margin evaluation in HNC patients. We determined the optimal cetuximab-800CW dose by quantification of intrinsic fluorescence values using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy. Methods: Five cohorts of three HNC patients received cetuximab-800CW systemically: three single dose cohorts (10, 25, 50 mg) and two cohorts pre-dosed with 75 mg unlabeled cetuximab (15 or 25 mg). Fluorescence visualization and MDSFR/SFF spectroscopy quantification was performed and were correlated to histopathology. Results: There were no study-related adverse events higher than Common Terminology Criteria for Adverse Events grade-II. Quantification of intrinsic fluorescence values showed a dose-dependent increase in background fluorescence in the single dose cohorts (p<0.001, p<0.001), which remained consistently low in the pre-dosed cohorts (p=0.6808). Resection margin status was evaluated with a sensitivity of 100% (4/4 tumor-positive margins) and specificity of 91% (10/11 tumor-negative margins). Conclusion: A pre-dose of 75 mg unlabeled cetuximab followed by 15 mg cetuximab-800CW was considered the optimal dose based on safety, fluorescence visualization and quantification of intrinsic fluorescence values. We were able to use a lower dose cetuximab-800CW than previously described, while remaining a high sensitivity for tumor detection due to application of equipment optimized for IRDye800CW detection, which was validated by quantification of intrinsic fluorescence values

Effect of Chemical Mutagens and Carcinogens on Gene Expression Profiles in Human TK6 Cells

Characterization of toxicogenomic signatures of carcinogen exposure holds significant promise for mechanistic and predictive toxicology. In vitro transcriptomic studies allow the comparison of the response to chemicals with diverse mode of actions under controlled experimental conditions. We conducted an in vitro study in TK6 cells to characterize gene expression signatures of exposure to 15 genotoxic carcinogens frequently used in European industries. We also examined the dose-responsive changes in gene expression, and perturbation of biochemical pathways in response to these carcinogens. TK6 cells were exposed at 3 dose levels for 24 h with and without S9 human metabolic mix. Since S9 had an impact on gene expression (885 genes), we analyzed the gene expression data from cells cultures incubated with S9 and without S9 independently. The ribosome pathway was affected by all chemical-dose combinations. However in general, no similar gene expression was observed among carcinogens. Further, pathways, i.e. cell cycle, DNA repair mechanisms, RNA degradation, that were common within sets of chemical-dose combination were suggested by clustergram. Linear trends in dose–response of gene expression were observed for Trichloroethylene, Benz[a]anthracene, Epichlorohydrin, Benzene, and Hydroquinone. The significantly altered genes were involved in the regulation of (anti-) apoptosis, maintenance of cell survival, tumor necrosis factor-related pathways and immune response, in agreement with several other studies. Similarly in S9+ cultures, Benz[a]pyrene, Styrene and Trichloroethylene each modified over 1000 genes at high concentrations. Our findings expand our understanding of the transcriptomic response to genotoxic carcinogens, revealing the alteration of diverse sets of genes and pathways involved in cellular homeostasis and cell cycle control