Analytic lymph node number establishes staging accuracy by occult tumor burden in colorectal cancer.

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden. METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category were defined by multivariable polytomous and semi-parametric polytomous logistic regression. RESULTS: Occult tumor burden stratified this pN0 cohort into categories of low (60%; recurrence rate (RR) = 2.3% [95% CI 0.1-4.5%]), intermediate (31%; RR = 33.3% [23.7-44.1%]), and high (9%; RR = 68.0% [46.5-85.1%], P \u3c 0.001) risk of recurrence. Beyond race and T stage, the number of analytic nodes was an independent marker of risk category (P \u3c 0.001). When \u3e12 nodes were analyzed, occult tumor burden almost completely resolved prognostic risk classification of pN0 patients. CONCLUSIONS: The prognostic utility of occult tumor burden assessed by GUCY2C RT-qPCR is dependent on the number of analytic lymph nodes

Realistic fluids as source for dynamically accreting black holes in a cosmological background

We show that a single imperfect fluid can be used as a source to obtain the generalized McVittie metric as an exact solution to Einstein's equations. The mass parameter in this metric varies with time thanks to a mechanism based on the presence of a temperature gradient. This fully dynamical solution is interpreted as an accreting black hole in an expanding universe if the metric asymptotes to Schwarzschild-de Sitter at temporal infinity. We present a simple but instructive example for the mass function and briefly discuss the structure of the apparent horizons and the past singularity.Comment: 5 pages, 2 figures. Updated references and minor changes to match the version accepted for publishing in PR

On the motion of particles in covariant Horava-Lifshitz gravity and the meaning of the A-field

We studied the low energy motion of particles in the general covariant version of Horava-Lifshitz gravity proposed by Horava and Melby-Thompson. Using a scalar field coupled to gravity according to the minimal substitution recipe proposed by da Silva and taking the geometrical optics limit, we could write an effective relativistic metric for a general solution. As a result, we discovered that the equivalence principle is not in general recovered at low energies, unless the spatial Laplacian of A vanishes. Finally, we analyzed the motion on the spherical symmetric solution proposed by Horava and Melby-Thompson, where we could find its effective line element and compute spin-0 geodesics. Using standard methods we have shown that such an effective metric cannot reproduce Newton's gravity law even in the weak gravitational field approximation.Comment: New result about equivalence principle added, improved discussion and typos corrected. Version to appear in Phys. Lett.

Hydroxylation of N-acetylneuraminic Acid Influences the in vivo Tropism of N-linked Sialic Acid-Binding Adeno-Associated Viruses AAV1, AAV5, and AAV6

Adeno-associated virus (AAV) vectors are promising candidates for gene therapy. However, a number of recent preclinical large animal studies failed to translate into the clinic. This illustrates the formidable challenge of choosing the animal models that promise the best chance of a successful translation into the clinic. Several of the most common AAV serotypes use sialic acid (SIA) as their primary receptor. However, in contrast to most mammals, humans lack the enzyme CMAH, which hydroxylates cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac) into cytidine monophosphate-N-glycolylneuraminic acid (CMP-Neu5Gc). As a result, human glycans only contain Neu5Ac and not Neu5Gc. Here, we investigate the tropism of AAV1, 5, 6 and 9 in wild-type C57BL/6J (WT) and CMAH knock-out (CMAH−/−) mice. All N-linked SIA-binding serotypes (AAV1, 5 and 6) showed significantly lower transduction of the heart in CMAH−/− when compared to WT mice (5–5.8-fold) and, strikingly, skeletal muscle transduction by AAV5 was almost 30-fold higher in CMAH−/− compared to WT mice. Importantly, the AAV tropism or distribution of expression among different organs was also affected. For AAV1, AAV5 and AAV6, expression in the heart compared to the liver was 4.6–8-fold higher in WT than in CMAH−/− mice, and for AAV5 the expression in the heart compared to the skeletal muscle was 57.3-fold higher in WT than in CMAH−/− mice. These data thus strongly suggest that the relative abundance of Neu5Ac and Neu5Gc plays a role in AAV tropism, and that results obtained in commonly used animal models might not translate into the clinic.Fil: Lopez Gordo, Estrella. Icahn School of Medicine ; Estados UnidosFil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Icahn School of Medicine ; Estados UnidosFil: Wang, Arthur. Icahn School of Medicine ; Estados UnidosFil: Weinberg, Alan. Icahn School of Medicine ; Estados UnidosFil: Sahoo, Susmita. Icahn School of Medicine ; Estados UnidosFil: Weber, Thomas. Icahn School of Medicine ; Estados Unido

Association of GUCY2C expression in lymph nodes with time to recurrence and disease-free survival in pN0 colorectal cancer.

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk. OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients with pN0 colorectal cancer enrolled between March 2002 and June 2007 at 9 US and Canadian centers (7 academic medical centers and 2 community hospitals) provided 2570 fresh lymph nodes measuring 5 mm or larger for histopathology and GUCY2C messenger RNA analysis. Patients were followed up for a median of 24 months (range, 2-63 months) for disease recurrence or death. MAIN OUTCOME MEASURES: Time to recurrence (primary outcome) and disease-free survival (secondary outcome) relative to expression of GUCY2C in lymph nodes. RESULTS: Thirty-two patients (12.5%) had lymph nodes negative for GUCY2C (pN0 [mol-]), and all but 2 remained free of disease during follow-up (recurrence rate, 6.3%; 95% confidence interval [CI], 0.8%-20.8%). Conversely, 225 patients (87.5%) had lymph nodes positive for GUCY2C (pN0 [mol+]), and 47 developed recurrent disease (20.9%; 95% CI, 15.8%-26.8%) (P = .006). Multivariate analyses revealed that GUCY2C in lymph nodes was an independent marker of prognosis. Patients who were pN0 (mol+) exhibited earlier time to recurrence (adjusted hazard ratio, 4.66; 95% CI, 1.11-19.57; P = .04) and reduced disease-free survival (adjusted hazard ratio, 3.27; 95% CI, 1.15-9.29; P = .03). CONCLUSION: Expression of GUCY2C in histologically negative lymph nodes appears to be independently associated with time to recurrence and disease-free survival in patients with pN0 colorectal cancer

Unparticle Induced Baryon Number Violating Nucleon Decays

We study baryon number violating nucleon decays induced by unparticle interactions with the standard model particles. We find that the lowest dimension operators which cause nucleon decays can arise at dimension 6 + (d_s-3/2) with the unparticles being a spinor of dimension d_s=d_\U +1/2. For scalar and vector unparticles of dimension d_\U, the lowest order operatoers arise at 6+d_\U and 7+d_\U dimensions,respectively. Comparing the spinor unparticle induced n \to O^s_\U and experimental bound on invisible decay of a neutron from KamLAND, we find that the scale for unparticle physics is required to be larger than 10^{10} GeV for d_\U < 2 if the couplings are set to be of order one. For scalar and vector unparticles, the dominant baryon number violating decay modes are n\to \bar \nu + O_\U (O^\mu_\U) and p \to e^+ + O_\U (O^\mu_\U). The same experimental bound puts the scales for scalar and vector unparticle to be larger than 10^{7} and 10^{5} GeV for d_\U <2 with couplings set to be of order one. Data on, p \to e^+ invisible, puts similar constraints on unparticle interactions.Comment: Latex 10 pages with two figure

A randomized double-blind study of the effect of triiodothyronine on cardiac function and morbidity after coronary bypass surgery

AbstractBackground: Although triiodothyronine deficiency has been described after cardiopulmonary bypass, data supporting its use have been conflicting. A double-blind, randomized, placebo-controlled study was undertaken to further define the effect of triiodothyronine on hemodynamics and outcome after coronary artery bypass grafting. Methods: A total of 170 patients undergoing elective coronary artery bypass grafting were enrolled and completed the study from November 1996 through March 1998. On removal of the aortic crossclamp, patients were randomized to receive either intravenous triiodothyronine (0.4 μg/kg bolus plus 0.1 μg/kg infusion administered over a 6-hour period, n = 81) or placebo (n = 89). Outcome variables included hemodynamic profile and inotropic drug/pressor requirements at several time points (mean ± standard error of the mean), perioperative morbidity (arrhythmia/ischemia/infarction), and mortality. Results: Despite similar baseline characteristics, patients randomized to triiodothyronine had a higher cardiac index and lower inotropic requirements after the operation. Subjects receiving triiodothyronine demonstrated a significantly lower incidence of postoperative myocardial ischemia (4% vs 18%, P = .007) and pacemaker dependence (14% vs 25%, P = .013). Seven patients in the placebo group required postoperative mechanical assistance (intra-aortic balloon pump, n = 4; left ventricular assist device, n = 3), compared with none in the triiodothyronine group (P = .01). There were 2 deaths in the placebo group and no deaths in the triiodothyronine group. Conclusions: Parenteral triiodothyronine given after crossclamp removal during elective coronary artery bypass grafting significantly improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, and decreased the incidence of myocardial ischemia. The incidence of atrial fibrillation was slightly decreased, and the need for postoperative pacemaker support was reduced. (J Thorac Cardiovasc Surg 1999;117:1128-35

Exploring the NRO Opportunity for a Hubble-sized Wide-field Near-IR Space Telescope -- NEW WFIRST

We discuss scientific, technical and programmatic issues related to the use of an NRO 2.4m telescope for the WFIRST initiative of the 2010 Decadal Survey. We show that this implementation of WFIRST, which we call "NEW WFIRST," would achieve the goals of the NWNH Decadal Survey for the WFIRST core programs of Dark Energy and Microlensing Planet Finding, with the crucial benefit of deeper and/or wider near-IR surveys for GO science and a potentially Hubble-like Guest Observer program. NEW WFIRST could also include a coronagraphic imager for direct detection of dust disks and planets around neighboring stars, a high-priority science and technology precursor for future ambitious programs to image Earth-like planets around neighboring stars.Comment: 76 pages, 26 figures -- associated with the Princeton "New Telescope Meeting

Clipping the Cosmos: The Bias and Bispectrum of Large Scale Structure

A large fraction of the information collected by cosmological surveys is simply discarded to avoid lengthscales which are difficult to model theoretically. We introduce a new technique which enables the extraction of useful information from the bispectrum of galaxies well beyond the conventional limits of perturbation theory. Our results strongly suggest that this method increases the range of scales where the relation between the bispectrum and power spectrum in tree-level perturbation theory may be applied, from k_max ~ 0.1 h/Mpc to ~ 0.7 h/Mpc. This leads to correspondingly large improvements in the determination of galaxy bias. Since the clipped matter power spectrum closely follows the linear power spectrum, there is the potential to use this technique to probe the growth rate of linear perturbations and confront theories of modified gravity with observation.Comment: 5 pages, 2 figures. To appear in Physical Review Letter