EarlyR: A Robust Gene Expression Signature for Predicting Outcomes of Estrogen Receptor–Positive Breast Cancer

Introduction Early stage estrogen receptor (ER)-positive breast cancer may be treated with chemotherapy in addition to hormone therapy. Currently available molecular signatures assess the risk of recurrence and the benefit of chemotherapy; however, these tests may have large intermediate risk groups, limiting their usefulness. Methods The EarlyR prognostic score was developed using integrative analysis of microarray data sets and formalin-fixed, paraffin-embedded–based quantitative real-time PCR assay and validated in Affymetrix data sets and METABRIC cohort using Cox proportional hazards models and Kaplan-Meier survival analysis. Concordance index was used to measure the probability of prognostic score agreement with outcome. Results The EarlyR score and categorical risk strata (EarlyR-Low, EarlyR-Int, EarlyR-High) derived from expression of ESPL1, MKI67, SPAG5, PLK1 and PGR was prognostic of 8-year distant recurrence-free interval in Affymetrix (categorical P = 3.5 × 10−14; continuous P = 8.8 × 10−15) and METABRIC (categorical P < 2.2 × 10−16; continuous P < 10−16) data sets of ER+ breast cancer. Similar results were observed for the breast cancer–free interval end point. At most 13% of patients were intermediate risk and at least 66% patients were low risk in both ER+ cohorts. The EarlyR score was significantly prognostic (distant recurrence-free interval; P < .001) in both lymph node–negative and lymph node–positive patients and was independent from clinical factors. EarlyR and surrogates of current molecular signatures were comparable in prognostic significance by concordance index. Conclusion The 5-gene EarlyR score is a robust prognostic assay that identified significantly fewer patients as intermediate risk and more as low risk than currently available assays. Further validation of the assay in clinical trial–derived cohorts is ongoing

Serum Amyloid Beta42 Is Not Eliminated by the Cirrhotic Liver: A Pilot Study.

Amyloid-beta (Aβ) deposition in the brain is the main pathological hallmark of Alzheimer disease. Peripheral clearance of Aβ may possibly also lower brain levels. Recent evidence suggested that hepatic clearance of Aβ42 is impaired in liver cirrhosis. To further test this hypothesis, serum Aβ42 was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS), and hepatic venous serum (HVS) of 20 patients with liver cirrhosis. Mean Aβ42 level was 24.7 ± 20.4 pg/mL in PVS, 21.2 ± 16.7 pg/mL in HVS, and 19.2 ± 11.7 pg/mL in SVS. Similar levels in the three blood compartments suggested that the cirrhotic liver does not clear Aβ42. Aβ42 was neither associated with the model of end-stage liver disease score nor the Child-Pugh score. Patients with abnormal creatinine or bilirubin levels or prolonged prothrombin time did not display higher Aβ42 levels. Patients with massive ascites and patients with large varices had serum Aβ42 levels similar to patients without these complications. Serum Aβ42 was negatively associated with connective tissue growth factor levels (r = -0.580, p = 0.007) and a protective role of Aβ42 in fibrogenesis was already described. Diabetic patients with liver cirrhosis had higher Aβ42 levels (p = 0.069 for PVS, p = 0.047 for HVS and p = 0.181 for SVS), which is in accordance with previous reports. Present analysis showed that the cirrhotic liver does not eliminate Aβ42. Further studies are needed to explore the association of liver cirrhosis, Aβ42 levels, and cognitive dysfunction

Assessing the Lifetime Performance of the Lightning Imaging Sensor (LIS): Implications for the Geostationary Lightning Mapper (GLM)

The Lightning Imaging Sensor (LIS) onboard the Tropical Rainfall Measuring Mission (TRMM) satellite has been providing observations of total lightning over the Earth s Tropics for 13 years. This study examines the performance of the LIS throughout its time in orbit. Application of the Deep Convective Cloud Technique (DCCT) (Doelling et al., 2004) was performed on the LIS background pixels to assess the stability of the LIS instrument. The DCCT analysis indicates that the maximum deviation of the monthly mean radiance is within 2% of the overall mean, indicating stable performance over the period. In addition, an examination of the number of flashes detected over time similarly shows no significant trend (after adjusting for the orbit boost that occurred in August 2001). These and other results indicate that there has been no discernible change in LIS performance throughout its lifetime. A similar approach will used for monitoring the performance of the Geostationary Lightning Mapper (GLM) onboard the next generation Geostationary Operational Environmental Satellite-R (GOES-R). Since GLM is based on LIS design heritage, the LIS results indicate that GLM may also experience stable performance over its lifetime

Dynamical spin-flip susceptibility for a strongly interacting ultracold Fermi gas

The Stoner model predicts that a two-component Fermi gas at increasing repulsive interactions undergoes a ferromagnetic transition. Using the random-phase approximation we study the dynamical properties of the interacting Fermi gas. For an atomic Fermi gas under harmonic confinement we show that the transverse (spin-flip) dynamical susceptibility displays a clear signature of the ferromagnetic phase in a magnon peak emerging from the Stoner particle-hole continuum. The dynamical spin susceptibilities could be experimentally explored via spin-dependent Bragg spectroscopy.Comment: 4 pages, 3 figure

Observations of Lightning on Earth from the Lunar Surface

The NASA Optical Transient Detector (OTD) launched into a 70deg inclination orbit in April 1995 aboard the MicroLab-1 satellite and the Lightning Imaging Sensor (LIS) launched into a 35deg inclination orbit in November 1997 (and still operating today) aboard the Tropical Rainfall Measuring Mission have produced the most comprehensive global observations of lightning activity on Earth. The OTD collected data for 5-yr from an altitude of 740 km while the LIS, in its 10th year of operations, is still collecting data from its current altitude of 402 km. From these altitudes the OTD observes an individual storm within its field of view for approx.3 min and the LIS for approx.90 sec as the satellites orbit the earth. Figures 1-4 show the combined LIS/OTD distribution of lightning for day and night during the Northern Hemisphere warm season from April through August (Fig. 1,2) and the cool season from October through February (Fig. 3,4) as might be observed from the lunar surface (12-h daylight and 12-h nighttime observations). The day and night plots are for the twelve hour periods centered on local noon and midnight. The total viewtime of the global lightning activity is 200 hours or less, depending on latitude (Fig. 5). Most of the observed lightning occurs over the northern hemisphere land areas as reported in previous studies. More lightning activity is seen at the higher northern latitudes during the day. The greatest lightning maxima occurs in the southeastern US, during the day. The corresponding region at night shows much less lightning activity. In contrast, there is a maxima in lightning activity at night over the high Plains area of the U.S. This region had lower lightning rates during the daytime period. During the cold season, the southern hemisphere has significantly more lightning. The maxima in Central Africa is still present, and a secondary maxima is observed in South Africa. In South America, the maxima in Argentina occurs at night in association with large-scale mesoscale convective storm complexes. This is the region on the earth having the greatest frequency of extreme storms with flash rates exceeding 1000 flashes/min. daytime maxima is seen extending from Northern Argentina to Brazil. In the US., the Gulf of Mexico and the Gulf Coast states exhibit a maximum in lightning activity both day and night

Lightning Imaging Sensor (LIS) on the International Space Station (ISS): Path to Attaining Level 1 Science Requirements and Early Results in Year One

No abstract availabl

Global Lightning Statistics from Two Years of Science Observations by the Lightning Imaging Sensor (LIS) on the International Space Station (ISS)

No abstract availabl

Disorder-induced magnetic memory: Experiments and theories

Beautiful theories of magnetic hysteresis based on random microscopic disorder have been developed over the past ten years. Our goal was to directly compare these theories with precise experiments. We first developed and then applied coherent x-ray speckle metrology to a series of thin multilayer perpendicular magnetic materials. To directly observe the effects of disorder, we deliberately introduced increasing degrees of disorder into our films. We used coherent x-rays to generate highly speckled magnetic scattering patterns. The apparently random arrangement of the speckles is due to the exact configuration of the magnetic domains in the sample. In effect, each speckle pattern acts as a unique fingerprint for the magnetic domain configuration. Small changes in the domain structure change the speckles, and comparison of the different speckle patterns provides a quantitative determination of how much the domain structure has changed. How is the magnetic domain configuration at one point on the major hysteresis loop related to the configurations at the same point on the loop during subsequent cycles? The microscopic return-point memory(RPM) is partial and imperfect in the disordered samples, and completely absent when the disorder was not present. We found the complementary-point memory(CPM) is also partial and imperfect in the disordered samples and completely absent when the disorder was not present. We found that the RPM is always a little larger than the CPM. We also studied the correlations between the domains within a single ascending or descending loop. We developed new theoretical models that do fit our experiments.Comment: 26 pages, 25 figures, Accepted by Physical Review B 01/25/0

Experimental Review of Baryons in the Nuclear Medium

Inclusive studies of nuclear photoabsorption have provided clear evidence of medium modifications but the results have not yet been explained in a model independent way. A deeper understanding of the situation is anticipated from a detailed experimental study of meson photoproduction from nuclei in exclusive reactions. Recent results on meson production in photonuclear experiments indicate a large difference between quasifree meson production from the nuclear surface and non-quasifree components.Comment: Proceedings Baryons200

Disorder-induced microscopic magnetic memory

Using coherent x-ray speckle metrology, we have measured the influence of disorder on major loop return point memory (RPM) and complementary point memory (CPM) for a series of perpendicular anisotropy Co/Pt multilayer films. In the low disorder limit, the domain structures show no memory with field cycling--no RPM and no CPM. With increasing disorder, we observe the onset and the saturation of both the RPM and the CPM. These results provide the first direct ensemble-sensitive experimental study of the effects of varying disorder on microscopic magnetic memory and are compared against the predictions of existing theories.Comment: 4 pages, 4 figures. Accepted for publication in Physical Review Letters in Nov. 200