We have investigated the variation of magnetic helicity over a span of several days around the times of 11 X-class flares which occurred in seven active regions (NOAA 9672, 10030, 10314, 10486, 10564, 10696, and 10720) using the magnetograms taken by the Michelson Doppler Imager (MDI ) on board the Solar and Heliospheric Observatory (SOHO). As a major result we found that each of these major flares was preceded by a significant helicity accumulation, (1:8Y16) ; 10 42 Mx 2 over a long period (0.5 to a few days). Another finding is that the helicity accumulates at a nearly constant rate, (4:5Y 48) ; 10 40 Mx 2 hr À1 , and then becomes nearly constant before the flares. This led us to distinguish the helicity variation into two phases: a phase of monotonically increasing helicity and the following phase of relatively constant helicity. As expected, the amount of helicity accumulated shows a modest correlation with timeintegrated soft X-ray flux during flares. However, the average helicity change rate in the first phase shows even stronger correlation with the time-integrated soft X-ray flux. We discuss the physical implications of this result and the possibility that this characteristic helicity variation pattern can be used as an early warning sign for solar eruptions.

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Conventional development of multivariate gene expression models (GEM) predicting therapeutic response of cancer patients is based on analysis of patients treated with specific regimens, which limits generalization to different or novel drug combinations. We overcome this limitation by developing GEMs based on in vitro drug sensitivities and microarray analyses of the NCI-60 cancer cell line panel. These GEMs were evaluated in blind fashion as predictors of tumor response and/or patient survival in seven independent cohorts of patients with breast (n = 275), bladder (n = 59), and ovarian (n = 143) cancer treated with multiagent chemotherapy, of which 233 patients were from prospectively enrolled clinical trials. In all studies, GEMs effectively stratified tumor response and patient survival independent of established clinical and pathologic tumor variables. In bladder cancer patients treated with neoadjuvant methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin, the 3-year overall survival for those with favorable GEM scores was 81% versus 33% for those with less favorable scores (P = 0.002). GEMs for breast cancer patients treated with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide and ovarian cancer patients treated with platinum-containing regimens also stratified patient survival [5-year overall survival 100% versus 74% (P = 0.05) and 3-year overall survival 68% versus 43% (P = 0.008), respectively]. Importantly, clinical prediction using our in vitro GEM was superior to that of conventionally derived GEMs. We show a facile yet effective approach to GEM derivation that identifies patients most likely to benefit from selected multiagent therapy. Use of such in vitro-based GEMs may provide a robust and generalizable approach to personalized cancer therapy. [Cancer Res 2009;69(21):8302-9]

A significant proportion of patients with low-risk prostate cancer as defined by D'Amico et al.'s classification diagnosed via multi-core prostate biopsy in contemporary period may have Gleason score upgrading following RRP. For patients with low-risk prostate cancer, preoperative PSA level and number of positive cores may be useful predictors of Gleason score upgrading, which was observed to significantly associated with other adverse pathologic features.

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