Prognostic and predictive value of androgen receptor expression in postmenopausal women with estrogen receptor-positive breast cancer : results from the Breast International Group Trial 1-98

The androgen receptor (AR) is an emerging prognostic marker and therapeutic target in breast cancer. AR is expressed in 60-80% of breast cancers, with higher prevalence among estrogen receptor-positive (ER+) tumors. Androgen treatment inhibits ER signaling in ER+/AR+ breast cancer cell lines, and AR expression is associated with improved survival for this subtype in epidemiologic studies. However, whether AR expression modifies the efficacy of selective ER modulators or aromatase inhibitors for ER+ cancers remains unclear

Distinguishing contributions to diffuse CO2 emissions in volcanic areas from magmatic degassing and thermal decarbonation using soil gas 222Rn-δ13C systematics: Application to Santorini volcano, Greece

Between January 2011 and April 2012, Santorini volcano (Greece) experienced a period of unrest characterised by the onset of detectable seismicity and caldera-wide uplift. This episode of inflation represented the first sizeable intrusion of magma beneath Santorini in the past 50 years. We employ a new approach using 222Rn-δ13C systematics to identify and quantify the source of diffuse degassing at Santorini during the period of renewed activity. Soil CO2 flux measurements were made across a network of sites on Nea Kameni between September 2010 and January 2012. Gas samples were collected in April and September 2011 for isotopic analysis of CO2 (δ13C), and radon detectors were deployed during September 2011 to measure (222Rn). Our results reveal a change in the pattern of degassing from the summit of the volcano (Nea Kameni) and suggest an increase in diffuse CO2 emissions between September 2010 and January 2012. High-CO2-flux soil gas samples have δ13C ~ 0‰. Using this value and other evidence from the literature we conclude that these CO2 emissions from Santorini were a mixture between CO2 sourced from magma, and CO2 released by the thermal or metamorphic breakdown of crustal limestone. We suggest that this mixing of magmatic and crustal carbonate sources may account more broadly for the typical range of δ13C values of CO2 (from ~ - 4‰ to ~ + 1‰) in diffuse volcanic and fumarole gas emissions around the Mediterranean, without the need to invoke unusual mantle source compositions. At Santorini a mixing model involving magmatic CO2 (with δ13C of -3 ± 2‰ and elevated (222Rn)/CO2 ratios ~105-106 Bqkg -1) and CO2 released from decarbonation of crustal limestone (with (222Rn)/CO2 ~ 30-300 Bqkg-1, and δ13C of +5‰) can account for the δ13C and (222Rn)/CO2 characteristics of the 'high flux' gas source. This model suggests ~60% of the carbon in the high flux deep CO2 end member is of magmatic origin. This combination of δ13C and (222Rn) measurements has potential to quantify magmatic and crustal contributions to the diffuse outgassing of CO2 in volcanic areas, especially those where breakdown of crustal limestone is likely to contribute significantly to the CO2 flux. © 2013 Elsevier B.V

From quiescence to unrest: 20 years of satellite geodetic measurements at Santorini volcano, Greece

Periods of unrest at caldera-forming volcanic systems characterized by increased rates of seismicity and deformation are well documented. Some can be linked to eventual eruptive activity, while others are followed by a return to quiescence. Here we use a 20 year record of interferometric synthetic aperture radar (InSAR) and GPS measurements from Santorini volcano to further our understanding of geodetic signals at a caldera-forming volcano during the periods of both quiescence and unrest, with measurements spanning a phase of quiescence and slow subsidence (1993-2010), followed by a phase of unrest (January 2011 to April 2012) with caldera-wide inflation and seismicity. Mean InSAR velocity maps from 1993-2010 indicate an average subsidence rate of ∼6 mm/yr over the southern half of the intracaldera island Nea Kameni. This subsidence can be accounted for by a combination of thermal contraction of the 1866-1870 lava flows and load-induced relaxation of the substrate. For the period of unrest, we use a joint inversion technique to convert InSAR measurements from three separate satellite tracks and GPS observations from 10 continuous sites into a time series of subsurface volume change. The optimal location of the inflating source is consistent with previous studies, situated north of Nea Kameni at a depth of ∼4 km. However, the time series reveals two distinct pressure pulses. The first pulse corresponds to a volume change (ΔV) within the shallow magma chamber of (11.56 ± 0.14) × 106 m3, and the second pulse has a ΔV of (9.73 ± 0.10) × 106 m3. The relationship between the timing of these pulses and microseismicity observations suggests that these pulses may be driven by two separate batches of magma supplied to a shallow reservoir. We find no evidence suggesting a change in source location between the two pulses. The decline in the rates of volume change at the end of both pulses and the observed lag of the deformation signal behind cumulative seismicity, suggest a viscoelastic response. We use a simple model to show that two separate pulses of magma intruding into a shallow magma chamber surrounded by a viscoelastic shell can account for the observed temporal variation in cumulative volume change and seismicity throughout the period of unrest. Given the similarities between the geodetic signals observed here and at other systems, this viscoelastic model has potential use for understanding behavior at other caldera systems. © 2013. The Authors

Further delineation of a recognizable type of syndromic short stature caused by biallelic SEMA3A loss-of-function variants

The semaphorin protein family is a diverse set of extracellular signaling proteins that perform fundamental roles in the development and operation of numerous biological systems, notably the nervous, musculoskeletal, cardiovascular, endocrine, and reproductive systems. Recently, recessive loss-of-function (LoF) variants in SEMA3A (semaphorin 3A) have been shown to result in a recognizable syndrome characterized by short stature, skeletal abnormalities, congenital heart defects, and variable additional anomalies. Here, we describe the clinical and molecular characterization of a female patient presenting with skeletal dysplasia, hypogonadotropic hypogonadism (HH), and anosmia who harbors a nonsense variant c.1633C\u3eT (p.Arg555*) and a deletion of exons 15, 16, and 17 in SEMA3A in the compound heterozygous state. These variants were identified through next-generation sequencing analysis of a panel of 26 genes known to be associated with HH/Kallmann syndrome. Our findings further substantiate the notion that biallelic LoF SEMA3A variants cause a syndromic form of short stature and expand the phenotypic spectrum associated with this condition to include features of Kallmann syndrome

Evolution of Santorini Volcano dominated by episodic and rapid fluxes of melt from depth

Santorini Volcano, the site of the catastrophic Minoan eruption in Greece, exhibits two distinct eruptive styles: small, effusive eruptions occur relatively frequently and build shields and domes of lava, whereas large explosive eruptions occur rarely, at intervals of 10,000-30,000 years. Both types of eruption were thought to incubate in a shallow magma chamber that is continually charged by small batches of melt injected into the chamber from below. However, petrological work suggests that at least 15% of the material ejected during the Minoan explosive eruption arrived in the magma chamber less than 100 years before the eruption. Here we use Satellite Radar Interferometry (InSAR) and Global Positioning System (GPS) measurements of surface deformation at Santorini to show that 10-20 million m 3 of magma have been intruded beneath the volcano since January 2011. This volume is equivalent to 10-50% of the volumes of recorded dome-forming eruptions. GPS and triangulation data show that this is the only volumetrically significant intrusion to have occurred since 1955, shortly after the last eruption. Our observations imply that whether Santorini is in an explosive or dome-forming phase, its shallow magma chamber is charged episodically by high-flux batches of magma. The durations of these events are short in comparison with the intervening periods of repose and their timing is controlled by the dynamics of deeper magma reservoirs

The emergence and growth of a submarine volcano: The Kameni islands, Santorini (Greece)

The morphology of a volcanic edifice reflects the integrated eruptive and evolutionary history of that system, and can be used to reconstruct the time-series of prior eruptions. We present a new high-resolution merged LiDAR-bathymetry grid, which has enabled detailed mapping of both onshore and offshore historic lava flows of the Kameni islands, emplaced in the centre of the Santorini caldera since at least AD 46. We identify three new submarine lava flows: two flows, of unknown age, lie to the east of Nea Kameni and a third submarine flow, located north of Nea Kameni appears to predate the 1925-1928 lava flows but was emplaced subsequent to the 1707-1711 lava flows. Yield strength estimates derived from the morphology of the 1570/1573 lobe suggest that submarine lava strengths are approximately two times greater than those derived from the onshore flows. To our knowledge this is the first documented yield strength estimate for submarine flows. This increase in strength is likely related to cooling and thickening of the dacite lava flows as they displace sea water. Improved lava volume estimates derived from the merged LiDAR-Bathymetry grid suggest typical lava extrusion rates of ~2-3m3s-1 during four of the historic eruptions on Nea Kameni (1707-1711, 1866-1870, 1925-1928 and 1939-1941). They also reveal a linear relationship between the pre-eruption interval and the volume of extruded lava. These observations may be used to estimate the size of future dome-building eruptions at Santorini volcano, based on the time interval since the last significant eruption. © 2014 The Authors

The emergence and growth of a submarine volcano: The Kameni islands, Santorini (Greece)

The morphology of a volcanic edifice reflects the integrated eruptive and evolutionary history of that system, and can be used to reconstruct the time-series of prior eruptions. We present a new high-resolution merged LiDAR-bathymetry grid, which has enabled detailed mapping of both onshore and offshore historic lava flows of the Kameni islands, emplaced in the centre of the Santorini caldera since at least AD 46. We identify three new submarine lava flows: two flows, of unknown age, lie to the east of Nea Kameni and a third submarine flow, located north of Nea Kameni appears to predate the 1925–1928 lava flows but was emplaced subsequent to the 1707–1711 lava flows. Yield strength estimates derived from the morphology of the 1570/1573 lobe suggest that submarine lava strengths are approximately two times greater than those derived from the onshore flows. To our knowledge this is the first documented yield strength estimate for submarine flows. This increase in strength is likely related to cooling and thickening of the dacite lava flows as they displace sea water. Improved lava volume estimates derived from the merged LiDAR-Bathymetry grid suggest typical lava extrusion rates of ∼2–3 m3 s−1 during four of the historic eruptions on Nea Kameni (1707–1711, 1866–1870, 1925–1928 and 1939–1941). They also reveal a linear relationship between the pre-eruption interval and the volume of extruded lava. These observations may be used to estimate the size of future dome-building eruptions at Santorini volcano, based on the time interval since the last significant eruption