Comparative toxicity and effectiveness of trastuzumab-based chemotherapy regimens in older women with early-stage breast cancer

Purpose The combination of chemotherapy and trastuzumab is the standard of care for adjuvant treatment of human epidermal growth factor receptor 2-positive breast cancer. Two regimens have been widely adopted in the United States: doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH) and docetaxel, carboplatin, and trastuzumab (TCH). No head-to-head comparison of these regimens has been conducted in a clinical trial, and existing trial data have limited generalizability to older patients. Methods We used SEER-Medicare data from 2005 to 2013 to compare outcomes of ACTH versus TCH among patients age older than 65 years. Propensity score matching was used to balance cohort characteristics between treatment arms. Outcomes included toxicity-related hospitalization, survival, and trastuzumab completion. Data from 1,077 patients receiving ACTH or TCH were analyzed, and the propensity-matched subsample included 416 women. Results There was a significant shift toward TCH over time, with 88% of patients receiving ACTH in 2005 compared with 15% by 2011. Among propensity score-matched patients, we found no difference between regimens in health care use overall or for chemotherapy-related adverse events (ACTH, 34% v TCH, 36.5%; P = .46). Patients receiving TCH were significantly more likely to complete trastuzumab (89% v 77%; P = .001). There was no difference in 5-year breast cancer-specific survival (ACTH, 92% v TCH, 96%; hazard ratio, 2.08; 95% CI, 0.90 to 4.82) or overall survival. Conclusion Among a matched sample of older patients, ACTH compared with TCH was not associated with a higher rate of serious adverse events or hospitalizations, but it was associated with less completion of adjuvant trastuzumab.Wedid not detect a difference in 5-year survival outcomes for ACTH compared with TCH. In the context of limited evidence in older patients, selection between these two regimens on the basis of concerns about differential toxicity or efficacy may not be appropriate

Analytic and Reidemeister torsion for representations in finite type Hilbert modules

For a closed Riemannian manifold we extend the definition of analytic and Reidemeister torsion associated to an orthogonal representation of fundamental group on a Hilbert module of finite type over a finite von Neumann algebra. If the representation is of determinant class we prove, generalizing the Cheeger-M\"uller theorem, that the analytic and Reidemeister torsion are equal. In particular, this proves the conjecture that for closed Riemannian manifolds with positive Novikov-Shubin invariants, the L2 analytic and Reidemeister torsions are equal.Comment: 78 pages, AMSTe

Reduction in blood pressure for elevated blood pressure/stage 1 hypertension according to the American College of Cardiology/American Heart Association guideline and cardiovascular outcomes

Aims Few studies have examined the relationship of blood pressure (BP) change in adults with elevated BP or stage 1 hypertension according to the American College of Cardiology (ACC)/American Heart Association (AHA) guideline with cardiovascular outcomes. We sought to identify the effect of BP change among individuals with elevated BP or stage 1 hypertension on incident heart failure (HF) and other cardiovascular diseases (CVDs). Methods We conducted a retrospective cohort study including 616 483 individuals (median age 46 years, 73.7% men) with elevated and results BP or stage 1 hypertension based on the ACC/AHA BP guideline. Participants were categorized using BP classification at one-year as normal BP (n = 173 558), elevated BP/stage 1 hypertension (n = 367 454), or stage 2 hypertension (n = 75 471). The primary outcome was HF, and the secondary outcomes included (separately) myocardial infarction (MI), angina pectoris (AP), and stroke. Over a mean follow-up of 1097 ± 908 days, 10 544 HFs, 1317 MIs, 11 070 APs, and 5198 strokes were recorded. Compared with elevated BP/stage 1 hypertension at one-year, normal BP at one-year was associated with a lower risk of developing HF [hazard ratio (HR): 0.89, 95% CI:0.85–0.94], whereas stage 2 hypertension at one-year was associated with an elevated risk of developing HF (HR:1.43, 95% CI:1.36–1.51). This association was also present in other cardiovascular outcomes including MI, AP, and stroke. The relationship was consistent in all subgroups stratified by age, sex, baseline BP category, and overweight/obesity. Conclusion A one-year decline in BP was associated with the lower risk of HF, MI, AP, and stroke, suggesting the importance of lowering BP in individuals with elevated BP or stage 1 hypertension according to the ACC/AHA guideline to prevent the risk of developing CVD.</p

Evaporative thermal resistance and its influence on microscopic bubble growth

Simulations of the formation of small steam bubbles indicate that the rate of growth of bubbles is very sensitive to the rate of evaporation of the micro-layer of liquid beneath the bubble. Such evaporation is rapid, and is modelled as being driven by the large heat flux through the thin liquid layer caused by the difference in temperature between the solid–liquid interface, and the saturation temperature in the interior of the bubble. However, application of this approach to recent experimental measurements of Jung and Kim generated anomalous results. In this paper we demonstrate that a model of the micro-layer heat flux that includes an allowance for the finite evaporative thermal resistance is able to eliminate these anomalies. This evaporative thermal resistance is a consequence of near-interface molecular dynamics, characterised by a quantity termed ‘evaporation coefficient’. Whilst in most engineering applications evaporative thermal resistance is small compared to conductive resistance, here, with the micro-layer thickness ranging from a few microns down to zero, it becomes of considerable importance. Selection of a molecular ‘evaporation coefficient’ to restore consistency to the anomalous measurements allows a plausible numerical value to be inferred. For the several times and multiple locations studied, a fairly consistent value of between 0.02 and 0.1 is indicated, (for saturated water in laboratory conditions), which itself is consistent with earlier literature values of this rather difficult quantity. It is shown that the evaporative resistance always represents a large fraction of the conductive resistance, and for important phases of the process dominates it. The need for inclusion of this phenomenon in the micro-layer models used in bubble analysis is clear

Flares, wind and nebulae: the 2015 December mini-outburst of V404 Cygni

After more than 26 years in quiescence, the black hole transient V404 Cyg went into a luminous outburst in June 2015, and additional activity was detected in late December of the same year. Here, we present an optical spectroscopic follow-up of the December mini-outburst, together with X-ray, optical and radio monitoring that spanned more than a month. Strong flares with gradually increasing intensity are detected in the three spectral ranges during the ∼ 10 days following the Swift trigger. Our optical spectra reveal the presence of a fast outflowing wind, as implied by the detection of a P-Cyg profile (He i–5876 ˚A) with a terminal velocity of ∼ 2500 kms−1 . Nebularlike spectra – with an H α equivalent width of ∼ 500 ˚A – are also observed. All these features are similar to those seen during the main June 2015 outburst. Thus, the fast optical wind simultaneous with the radio jet is most likely present in every V404 Cyg outburst. Finally, we report on the detection of a strong radio flare in late January 2016, when X-ray and optical monitoring had stopped due to Sun constraints

A Rigorous Geometric Derivation of the Chiral Anomaly in Curved Backgrounds

We discuss the chiral anomaly for a Weyl field in a curved background and show that a novel index theorem for the Lorentzian Dirac operator can be applied to describe the gravitational chiral anomaly. A formula for the total charge generated by the gravitational and gauge field background is derived directly in Lorentzian signature and in a mathematically rigorous manner. It contains a term identical to the integrand in the Atiyah–Singer index theorem and another term involving the η -invariant of the Cauchy hypersurfaces

Proximity effect at superconducting Sn-Bi2Se3 interface

We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions down to 250 mK and in different magnetic fields. A number of conductance anomalies were observed below the superconducting transition temperature of Sn, including a small gap different from that of Sn, and a zero-bias conductance peak growing up at lower temperatures. We discussed the possible origins of the smaller gap and the zero-bias conductance peak. These phenomena support that a proximity-effect-induced chiral superconducting phase is formed at the interface between the superconducting Sn and the strong spin-orbit coupling material Bi2Se3.Comment: 7 pages, 8 figure

Centrality Dependence of the High p_T Charged Hadron Suppression in Au+Au collisions at sqrt(s_NN) = 130 GeV

PHENIX has measured the centrality dependence of charged hadron p_T spectra from central Au+Au collisions at sqrt(s_NN)=130 GeV. The truncated mean p_T decreases with centrality for p_T > 2 GeV/c, indicating an apparent reduction of the contribution from hard scattering to high p_T hadron production. For central collisions the yield at high p_T is shown to be suppressed compared to binary nucleon-nucleon collision scaling of p+p data. This suppression is monotonically increasing with centrality, but most of the change occurs below 30% centrality, i.e. for collisions with less than about 140 participating nucleons. The observed p_T and centrality dependence is consistent with the particle production predicted by models including hard scattering and subsequent energy loss of the scattered partons in the dense matter created in the collisions.Comment: 7 pages text, LaTeX, 6 figures, 2 tables, 307 authors, resubmitted to Phys. Lett. B. Revised to address referee concerns. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm