NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin and paclitaxel for patients with endometrial cancer.

BACKGROUND: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer. METHODS: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with \u3e50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). RESULTS: A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months. CONCLUSIONS: Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma

Impact of clinical characteristics on human chorionic gonadotropin regression after molar pregnancy

OBJECTIVES: This study aimed to determine the effects of age, race/ethnicity, body mass index, and contraception on human chorionic gonadotropin (hCG) regression following the evacuation of a molar pregnancy. METHODS: This was a retrospective cohort study of 277 patients with molar pregnancies between January 1, 1994 and December 31, 2015. The rate of hCG regression was estimated using mixed-effects linear regression models on daily log-transformed serum hCG levels after evacuation. RESULTS: There were no differences in hCG half-lives among age (p=0.13) or race/ethnicity (p=0.16) groups. Women with obesity and hormonal contraceptive use demonstrated faster hCG regression than their counterparts (3.2 versus. 3.7 days, p=0.02 and 3.4 versus. 4.0 days, p=0.002, respectively). CONCLUSION: Age and race/ethnicity were not associated with hCG regression rates. Hormonal contraceptive use and obesity were associated with shorter hCG half-lives, but with unlikely clinical significance. It is important to understand whether the clinical characteristics of patients may influence the hCG regression curve, as it has been proposed as a way to predict the risk of gestational trophoblastic neoplasia

Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI).

AIM: Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this double-blind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6-8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6-8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size -0.7% 95% CI: -2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6-8 days and at 6 months and final infarct size (FIS) measured at 6 months. CONCLUSIONS: Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size

The Entropy of 4D Black Holes and the Enhancon

We consider the physics of enhancons as applied to four dimensional black holes which are constructed by wrapping both D-branes and NS-branes on K3. As was recently shown for the five dimensional black holes, the enhancon is crucial in maintaining consistency with the second law of thermodynamics. This is true for both the D-brane and NS-brane sectors of these black holes. In particular NS5-branes in both type IIA and IIB string theory are found to exhibit enhancon physics when wrapped on a K3 manifold.Comment: 23 pages. 1 figure. Minor typos corrected. Refs added. To appear in PR

Quantum Fields in a Big Crunch/Big Bang Spacetime

We consider quantum field theory on a spacetime representing the Big Crunch/Big Bang transition postulated in the ekpyrotic or cyclic cosmologies. We show via several independent methods that an essentially unique matching rule holds connecting the incoming state, in which a single extra dimension shrinks to zero, to the outgoing state in which it re-expands at the same rate. For free fields in our construction there is no particle production from the incoming adiabatic vacuum. When interactions are included the total particle production for fixed external momentum is finite at tree level. We discuss a formal correspondence between our construction and quantum field theory on de Sitter spacetime.Comment: 30 pages, RevTex file, five postscript figure file

Cosmological Perturbations in a Big Crunch/Big Bang Space-time

A prescription is developed for matching general relativistic perturbations across singularities of the type encountered in the ekpyrotic and cyclic scenarios i.e. a collision between orbifold planes. We show that there exists a gauge in which the evolution of perturbations is locally identical to that in a model space-time (compactified Milne mod Z_2) where the matching of modes across the singularity can be treated using a prescription previously introduced by two of us. Using this approach, we show that long wavelength, scale-invariant, growing-mode perturbations in the incoming state pass through the collision and become scale-invariant growing-mode perturbations in the expanding hot big bang phase.Comment: 47 pages, 4 figure

Gyrotropic impact upon negatively refracting surfaces

Surface wave propagation at the interface between different types of gyrotropic materials and an isotropic negatively refracting medium, in which the relative permittivity and relative permeability are, simultaneously, negative is investigated. A general approach is taken that embraces both gyroelectric and gyromagnetic materials, permitting the possibility of operating in either the low GHz, THz or the optical frequency regimes. The classical transverse Voigt configuration is adopted and a complete analysis of non-reciprocal surface wave dispersion is presented. The impact of the surface polariton modes upon the reflection of both plane waves and beams is discussed in terms of resonances and an example of the influence upon the Goos–Hänchen shift is given

Dynamical Stability of Six-Dimensional Warped Brane-Worlds

We study a generalization of the Randall-Sundrum mechanism for generating the weak/Planck hierarchy, which uses two rather than one warped extra dimension, and which requires no negative tension branes. A 4-brane with one exponentially large compact dimension plays the role of the Planck brane. We investigate the dynamical stability with respect to graviton, graviphoton and radion modes. The radion is shown to have a tachyonic instability for certain models of the 4-brane stress-energy, while it is stable in others, and massless in a special case. If stable, its mass is in the milli-eV range, for parameters of the model which solve the hierarchy problem. The radion is shown to couple to matter with gravitational strength, so that it is potentially detectable by submillimeter-range gravity experiments. The radion mass can be increased using a bulk scalar field in the manner of Goldberger and Wise, but only to order MeV, due to the effect of the large extra dimension. The model predicts a natural scale of 10^{13} GeV on the 4-brane, making it a natural setting for inflation from the ultraviolet brane.Comment: 28 pages, 7 figure

Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI)

BACKGROUND: Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial. METHODS AND OUTCOMES: The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6-8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6-8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6-8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6-8 days and six months. FUNDING,ETHICS AND REGULATORY APPROVALS: This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26)

The Noncommutative Bion Core

We examine noncommutative solutions of the nonabelian theory on the world-volume of N coincident D-strings. These solutions can be interpreted in terms of noncommutative geometry as funnels describing the nonabelian D-string expanding out into an orthogonal D3-brane. These configurations are `dual' to the bion solutions in the abelian world-volume theory of the D3-brane. In the latter, a charge N magnetic monopole describes N D-strings attached to the D3-brane with a spike deformation of the world-volume. The noncommutative D-string solutions give a reliable account of physics at the core of the monopole, where the bion description is expected to breakdown. In the large N limit, we find good agreement between the two points of view, including the energy, couplings to background fields, and the shape of the funnel. We also study fluctuations traveling along the D-string, again obtaining agreement in the large N limit. At finite N, our results give a limit on the number of modes that can travel to infinity along the N D-strings attached to the D3-brane.Comment: 22 pages, refs adde