Assessing fracture risk in early stage breast cancer patients treated with aromatase-inhibitors: An enhanced screening approach incorporating trabecular bone score

AbstractIntroductionAromatase-inhibitors (AIs) are commonly used for treatment of patients with hormone-receptor positive breast carcinoma, and are known to induce bone density loss and increase the risk of fractures. The current standard-of-care screening tool for fracture risk is bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The fracture risk assessment tool (FRAX®) may be used in conjunction with BMD to identify additional osteopenic patients at risk of fracture who may benefit from a bone-modifying agent (BMA). The trabecular bone score (TBS), a novel method of measuring bone microarchitecture by DXA, has been shown to be an independent indicator of increased fracture risk. We report how the addition of TBS and FRAX®, respectively, to BMD contribute to identification of elevated fracture risk (EFR) in postmenopausal breast cancer patients treated with AIs.Methods100 patients with early stage hormone-positive breast cancer treated with AIs, no prior BMAs, and with serial DXAs were identified. BMD and TBS were measured from DXA images before and following initiation of AIs, and FRAX® scores were calculated from review of clinical records. EFR was defined as either: BMD ≤−2.5 or BMD between −2.5 and −1 plus either increased risk by FRAX® or degraded microstructure by TBS.ResultsAt baseline, BMD alone identified 4% of patients with EFR. The addition of FRAX® increased detection to 13%, whereas the combination of BMD, FRAX® and TBS identified 20% of patients with EFR. Following AIs, changes in TBS were independent of changes in BMD. On follow-up DXA, BMD alone detected an additional 1 patient at EFR (1%), whereas BMD+ FRAX® identified 3 additional patients (3%), and BMD+FRAX®+TBS identified 7 additional patients (7%).ConclusionsThe combination of FRAX®, TBS, and BMD maximized the identification of patients with EFR. TBS is a novel assessment that enhances the detection of patients who may benefit from BMAs

The Impact of the Spectral Response of an Achromatic Half-Wave Plate on the Measurement of the Cosmic Microwave Background Polarization

We study the impact of the spectral dependence of the linear polarization rotation induced by an achromatic half-wave plate on measurements of cosmic microwave background polarization in the presence of astrophysical foregrounds. We focus on the systematic effects induced on the measurement of inflationary gravitational waves by uncertainties in the polarization and spectral index of Galactic dust. We find that for the experimental configuration and noise levels of the balloon-borne EBEX experiment, which has three frequency bands centered at 150, 250, and 410 GHz, a crude dust subtraction process mitigates systematic effects to below detectable levels for 10% polarized dust and tensor to scalar ratio of as low as r = 0.01. We also study the impact of uncertainties in the spectral response of the instrument. With a top-hat model of the spectral response for each band, characterized by band-center and band-width, and with the same crude dust subtraction process, we find that these parameters need to be determined to within 1 and 0.8 GHz at 150 GHz; 9 and 2.0 GHz at 250 GHz; and 20 and 14 GHz at 410 GHz, respectively. The approach presented in this paper is applicable to other optical elements that exhibit polarization rotation as a function of frequency.Comment: 6 pages, 7 figures, accepted for publication by Astrophysical Journa

Mainshocks are aftershocks of conditional foreshocks: How do foreshock statistical properties emerge from aftershock laws

The inverse Omori law for foreshocks discovered in the 1970s states that the rate of earthquakes prior to a mainshock increases on average as a power law ~ 1/(t_c-t)^p' of the time to the mainshock occurring at t_c. Here, we show that this law results from the direct Omori law for aftershocks describing the power law decay ~ 1/(t-t_c)^p of seismicity after an earthquake, provided that any earthquake can trigger its suit of aftershocks. In this picture, the seismic activity at any time is the sum of the spontaneous tectonic loading and of the activity triggered by all preceding events weighted by their corresponding Omori law. The inverse Omori law then emerges as the expected (in a statistical sense) trajectory of seismicity, conditioned on the fact that it leads to the burst of seismic activity accompanying the mainshock. The often documented apparent decrease of the b-value of the GR law at the approach to the main shock results straightforwardly from the conditioning of the path of seismic activity culminating at the mainshock. In the space domain, we predict that the phenomenon of aftershock diffusion must have its mirror process reflected into an inward migration of foreshocks towards the mainshock. In this model, foreshock sequences are special aftershock sequences which are modified by the condition to end up in a burst of seismicity associated with the mainshock.Comment: Latex document of 35 pages, 10 figure