Clinical endpoints for the study of geographic atrophy secondary to age-related macular degeneration

Purpose: To summarize the recent literature describing the application of modern technologies in the study of patients with geographic atrophy (GA) secondary to age-related macular degeneration. Methods: Review of the literature describing the terms and definitions used to describe GA, imaging modalities used to capture and measure GA, and the tests of visual function and functional deficits that occur in patients with GA. Results: In this paper, we describe the evolution of the definitions used to describe GA. We compare imaging modalities used in the characterization of GA, report on the sensitivity and specificity of the techniques where data exist, and describe the correlations between these various modes of capturing the presence of GA. We review the functional tests that have been used in patients with GA, and critically examine their ability to detect and quantify visual deficits. Conclusion: Ophthalmologists and retina specialists now have a wide range of assessments available for the functional and anatomic characterization of GA in patients with age-related macular degeneration. To date, studies have been limited by their unimodal approach, and we recommend that future studies of GA use multimodal imaging. We also suggest strategies for the optimal functional testing of patients with GA

Electromagnetic Polarization Effects due to Axion Photon Mixing

We investigate the effect of axions on the polarization of electromagnetic waves as they propagate through astronomical distances. We analyze the change in the dispersion of the electromagnetic wave due to its mixing with axions. We find that this leads to a shift in polarization and turns out to be the dominant effect for a wide range of frequencies. We analyze whether this effect or the decay of photons into axions can explain the large scale anisotropies which have been observed in the polarizations of quasars and radio galaxies. We also comment on the possibility that the axion-photon mixing can explain the dimming of distant supernovae.Comment: 18 pages, 1 figur

Pressure-dependence of electron-phonon coupling and the superconducting phase in hcp Fe - a linear response study

A recent experiment by Shimizu et al. has provided evidence of a superconducting phase in hcp Fe under pressure. To study the pressure-dependence of this superconducting phase we have calculated the phonon frequencies and the electron-phonon coupling in hcp Fe as a function of the lattice parameter, using the linear response (LR) scheme and the full potential linear muffin-tin orbital (FP-LMTO) method. Calculated phonon spectra and the Eliashberg functions $\alpha^2 F$ indicate that conventional s-wave electron-phonon coupling can definitely account for the appearance of the superconducting phase in hcp Fe. However, the observed change in the transition temperature with increasing pressure is far too rapid compared with the calculated results. For comparison with the linear response results, we have computed the electron-phonon coupling also by using the rigid muffin-tin (RMT) approximation. From both the LR and the RMT results it appears that electron-phonon interaction alone cannot explain the small range of volume over which superconductivity is observed. It is shown that ferromagnetic/antiferromagnetic spin fluctuations as well as scattering from magnetic impurities (spin-ordered clusters) can account for the observed values of the transition temperatures but cannot substantially improve the agreeemnt between the calculated and observed presure/volume range of the superconducting phase. A simplified treatment of p-wave pairing leads to extremely small ($\leq 10^{-2}$ K) transition temperatures. Thus our calculations seem to rule out both $s$- and $p$- wave superconductivity in hcp Fe.Comment: 12 pages, submitted to PR

Breast cancer in patients with germline TP53 pathogenic variants have typical tumour characteristics: the Cohort study of TP53 carrier early onset breast cancer (COPE study)

Germline TP53 pathogenic variants are rare but associated with a high risk of cancer; they are often identified in the context of clinically diagnosed Li-Fraumeni syndrome predisposing to a range of young onset cancers including sarcomas and breast cancer. The study aim was to conduct a detailed morphological review and immuno-phenotyping of breast cancer arising in carriers of a germline TP53 pathogenic variant. We compared breast cancers from five defined groups: (1) TP53 carriers with breast cancer (n = 59), (2) early onset HER2-amplified breast cancer, no germline pathogenic variant in BRCA1/2 or TP53 (n = 55), (3) BRCA1 pathogenic variant carriers (n = 60); (4) BRCA2 pathogenic variant carriers (n = 61) and (5) young onset breast cancer with no known germline pathogenic variant (n = 98). Pathologists assessed a pre-agreed set of morphological characteristics using light microscopy. Immunohistochemistry (IHC) for HER2, ER, PR, p53, integrin alpha v beta 6 (αvβ6) integrin, α-smooth muscle actin (α-SMA) and pSMAD2/3 was performed on tissue microarrays of invasive carcinoma. We confirmed a previously reported high prevalence of HER2-amplified, ductal no special type invasive breast carcinoma amongst known TP53 germline pathogenic variant carriers 20 of 36 (56%). Furthermore we observed a high frequency of densely sclerotic tumour stroma in cancers from TP53 carriers (29/36, 80.6%) when compared with non-carriers, 50.9% (28/55), 34.7% (50/144), 41.4% (65/157), 43.8% (95/217) in groups 2-5 respectively. The majority of germline TP53 gene carrier breast tumours had a high intensity of integrin αvβ6, α-SMA and pSMAD2/3 expression in the majority of cancer cells. In conclusion, aggressive HER2 positive breast cancers with densely sclerotic stroma are common in germline TP53 carriers. High levels of αvβ6 integrin, α-SMA and pSMAD2/3 expression suggest that the dense stromal phenotype may be driven by upregulated transforming growth factor beta signalling.Kate Packwood, Guy Martland, Matthew Sommerlad, Emily Shaw, Karwan Moutasim ... Nicola Poplawski ... et al

Titan's cold case files - Outstanding questions after Cassini-Huygens

Abstract The entry of the Cassini-Huygens spacecraft into orbit around Saturn in July 2004 marked the start of a golden era in the exploration of Titan, Saturn's giant moon. During the Prime Mission (2004–2008), ground-breaking discoveries were made by the Cassini orbiter including the equatorial dune fields (flyby T3, 2005), northern lakes and seas (T16, 2006), and the large positive and negative ions (T16 & T18, 2006), to name a few. In 2005 the Huygens probe descended through Titan's atmosphere, taking the first close-up pictures of the surface, including large networks of dendritic channels leading to a dried-up seabed, and also obtaining detailed profiles of temperature and gas composition during the atmospheric descent. The discoveries continued through the Equinox Mission (2008–2010) and Solstice Mission (2010–2017) totaling 127 targeted flybys of Titan in all. Now at the end of the mission, we are able to look back on the high-level scientific questions from the start of the mission, and assess the progress that has been made towards answering these. At the same time, new scientific questions regarding Titan have emerged from the discoveries that have been made. In this paper we review a cross-section of important scientific questions that remain partially or completely unanswered, ranging from Titan's deep interior to the exosphere. Our intention is to help formulate the science goals for the next generation of planetary missions to Titan, and to stimulate new experimental, observational and theoretical investigations in the interim

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society