Strong disk winds traced throughout outbursts in black-hole X-ray binaries.

Recurring outbursts associated with matter flowing onto compact stellar remnants (such as black holes, neutron stars and white dwarfs) in close binary systems provide a way of constraining the poorly understood accretion process. The light curves of these outbursts are shaped by the efficiency of angular-momentum (and thus mass) transport in the accretion disks, which has traditionally been encoded in a viscosity parameter, α. Numerical simulations of the magneto-rotational instability that is believed to be the physical mechanism behind this transport yield values of α of roughly 0.1-0.2, consistent with values determined from observations of accreting white dwarfs. Equivalent viscosity parameters have hitherto not been estimated for disks around neutron stars or black holes. Here we report the results of an analysis of archival X-ray light curves of 21 outbursts in black-hole X-ray binaries. By applying a Bayesian approach to a model of accretion, we determine corresponding values of α of around 0.2-1.0. These high values may be interpreted as an indication either of a very high intrinsic rate of angular-momentum transport in the disk, which could be sustained by the magneto-rotational instability only if a large-scale magnetic field threads the disk, or that mass is being lost from the disk through substantial outflows, which strongly shape the outburst in the black-hole X-ray binary. The lack of correlation between our estimates of α and the accretion state of the binaries implies that such outflows can remove a substantial fraction of the disk mass in all accretion states and therefore suggests that the outflows correspond to magnetically driven disk winds rather than thermally driven ones, which require specific radiative conditions.

A New Diagnosis-Specific Survival Score for Patients to be Irradiated for Brain Metastases from Non-small Cell Lung Cancer.

INTRODUCTION: Personalized treatment helps one achieve optimal outcomes in patients with non-small cell lung cancer (NSCLC). Understanding patients' survival prognoses in a palliative situation like intracerebral metastases is critical. A new survival score, the WBRT-30-NSCLC, was developed for patients with intracerebral metastases from NSCLC. METHODS: Eight factors were investigated in 157 patients receiving 10 × 3 Gy of whole-brain radiotherapy (WBRT) including age, gender, Karnofsky performance score (KPS), interval from diagnosis of NSCLC to WBRT, pre-WBRT systemic treatment, primary tumor control, number of intracerebral metastases, and metastasis outside the brain. Factors significant (p < 0.05) or showing a trend (p < 0.08) on multivariate analysis were used for the WBRT-30-NSCLC. Patient scores were derived by adding factor scores (6-month survival rates divided by 10). WBRT-30-NSCLC was compared to other scores for intracerebral metastases from NSCLC. RESULTS: On multivariate analysis, age (p = 0.005), KPS (p < 0.001), systemic treatment (p = 0.018), and metastasis outside the brain (p < 0.001) were significant; number of intracerebral metastases (p = 0.075) showed a trend. Four groups were designed (912, 1317, 1820, and 22 points) with 6-month survival rates of 3, 26, 65, and 100%. Positive predictive value (PPV) to predict death ≤ 6 months after WBRT was 97% (updated DS-GPA classification 86%, Rades-NSCLC 88%), and PPV to predict survival ≥ 6 months was 100% (updated DS-GPA 78%, Rades-NSCLC 74%). CONCLUSIONS: The WBRT-30-NSCLC appeared very precise in identifying patients with intracerebral metastases from NSCLC dying ≤ 6 months or surviving ≥ 6 months. It appeared more precise than previous scores and can support physicians developing personalized treatment regimens.

High-resolution x-ray imaging of a globular cluster core: compact binaries in 47Tuc.

We have obtained high-resolution (approximately 1") deep x-ray images of the globular cluster 47Tucanae (NGC 104) with the Chandra X-ray Observatory to study the population of compact binaries in the high stellar density core. A 70-kilosecond exposure of the cluster reveals a centrally concentrated population of faint (Lx approximately 10(30-33) ergs per second) x-ray sources, with at least 108 located within the central 2' x 2.5' and greater, similar half with Lx approximately 10(30.5) ergs per second. All 15 millisecond pulsars (MSPs) recently located precisely by radio observations are identified, though 2 are unresolved by Chandra. The x-ray spectral and temporal characteristics, as well as initial optical identifications with the Hubble Space Telescope, suggest that greater, similar50 percent are MSPs, about 30 percent are accreting white dwarfs, about 15 percent are main-sequence binaries in flare outbursts, and only two to three are quiescent low-mass x-ray binaries containing neutron stars, the conventional progenitors of MSPs. An upper limit of about 470 times the mass of the sun is derived for the mass of an accreting central black hole in the cluster. These observations provide the first x-ray "color-magnitude" diagram for a globular cluster and census of its compact object and binary population.

Diagnosis-specific WBRT-30-CRC Score for Estimating Survival of Patients Irradiated for Brain Metastases from Colorectal Cancer.

BACKGROUND/AIM: Existing survival scores for patients with brain metastases were created in heterogeneously treated cohorts. A new score was developed in 56 patients with brain metastases from colorectal cancer treated with 10×3 Gy of whole-brain radiotherapy (WBRT). PATIENTS AND METHODS: Factors found significantly associated with survival (p<0.05) or showing a trend (p<0.08) were included in the tool. The new WBRT-30-CRC was compared to diagnosis-specific graded prognostic assessment (DS-GPA) classification for gastrointestinal cancers. RESULTS: The WBRT-30-CRC included four prognostic groups: 3-4, 5-6, 7-9 and 10 points. Six-month survival rates were 0%, 15%, 38% and 80%. PPV of the 3-4 points-group predicting death ≤6 months was 100% (91% for DS-GPA of 0.0-1.0). PPV of the 10 points-group predicting survival ≥6 months was 80% (0% DS-GPA of 3.5-4.0, 33% DS-GPA of 3.0-4.0). CONCLUSION: The WBRT-30-CRC appeared very precise in identifying patients with brain metastases from colorectal cancer dying ≤6 months or surviving ≥6 months.

Comparison of Diagnosis-Specific Survival Scores for Patients with Small-Cell Lung Cancer Irradiated for Brain Metastases.

Diagnosis-specific survival scores including a new score developed in 157 patients with brain metastases from small-cell lung cancer (SCLC) receiving whole-brain radiotherapy (WBRT) with 30 Gy in 10 fractions (WBRT-30-SCLC) were compared. Three prognostic groups were designed based on the 6-month survival probabilities of significant or almost significant factors, (age, performance score, number of brain metastases, extra-cerebral metastasis). Six-month survival rates were 6% (6⁻11 points), 44% (12⁻14 points) and 86% (16⁻19 points). The WBRT-30-SCLC was compared to three disease-specific scores for brain metastasis from SCLC, the original and updated diagnosis-specific graded prognostic assessment DS-GPA classifications and the Rades-SCLC. Positive predictive values (PPVs) used to correctly predict death ≤6 months were 94% (WBRT-30-SCLC), 88% (original DS-GPA), 88% (updated DS-GPA) and 100% (Rades-SCLC). PPVs to predict survival ≥6 months were 86%, 75%, 76% and 100%. For WBRT-30-SCLC and Rades-SCLC, differences between poor and intermediate prognoses groups and between intermediate and favorable prognoses groups were significant. For both DS-GPA classifications, only the difference between poor and intermediate prognoses groups was significant. Of these disease-specific tools, Rades-SCLC appeared to be the most accurate in identifying patients dying ≤6 months and patients surviving ≥6 months after irradiation, followed by the new WBRT-30-SCLC and the DS-GPA classifications.

Estimating Survival of Patients With Metastatic Renal Cell Carcinoma Receiving Whole-brain Radiotherapy With a New Tool.

BACKGROUND/AIM: A new tool for estimating survival of patients receiving whole-brain radiotherapy (WBRT) for intracerebral metastases from renal cell carcinoma (RCC) was created. PATIENTS AND METHODS: The new WBRT-30-RCC was developed in 34 patients homogeneously treated with 30 Gy in 10 fractions of WBRT and compared to updated diagnosis-specific graded prognostic assessment DS-GPA and Dziggel score for predicting death within 6 months and survival for at least 6 months following WBRT. RESULTS: WBRT-30-RCC included three groups with 6-month survival rates of 6.7% for those with 8-10 points, 38.5% for those with 12-14 points and 66.7% for those with 16-18 points. Positive predictive values (PPV)s for predicting death within 6 months were 93.3% using WBRT-30-RCC, 77.3% using updated DS-GPA and 93.7% using the Dziggel score. PPVs for predicting survival for at least 6 months were 66.7%, 50.0% and 50.0%, respectively. CONCLUSION: WBRT-30-RCC was more precise than the other scores in predicting survival for at least 6 months, although all three scores were not optimal. For predicting death within 6 months, WBRT-30-RCC and Dziggel score were similarly accurate and superior to the updated DS-GPA.

Potential Impact of the Interval Between Imaging and Whole-brain Radiotherapy in Patients With Relatively Favorable Survival Prognoses.

BACKGROUND/AIM: The interval between diagnostic imaging and whole-brain radiotherapy (WBRT) had no significant impact on survival in our previous study of WBRT for brain metastases. Since median survival time was only 2 months, a potentially negative impact by delaying treatment could have been missed. Therefore, we performed an additional analysis of patients surviving at least 4 months following irradiation. PATIENTS AND METHODS: The interval between diagnosis of brain metastases and WBRT and ten other factors were retrospectively analyzed for survival in 191 patients surviving 4 months or longer following WBRT. RESULTS: On univariate analyses, Eastern Cooperative Oncology Group (ECOG) performance score of 0-1, 1-3 brain metastases and absence of extra-cerebral metastases were significantly associated with longer survival, whereas the interval from diagnostic imaging to WBRT was not. On multivariate analysis, ECOG performance score remained significant, and extra-cerebral metastases showed a trend towards a longer survival. CONCLUSION: The interval between diagnostic imaging and WBRT didn't have a significant impact on patients surviving 4 months or longer. Depending on the need for symptom relief, WBRT may be postponed for very important reasons such as obtaining a multidisciplinary tumor board decision or definitive histology.

Comparison of Diagnosis-specific Survival Scores for Patients With Cerebral Metastases from Malignant Melanoma Including the New WBRT-30-MM.

BACKGROUND/AIM: Diagnosis-specific scoring systems developed for predicting survival of patients with cerebral metastases from malignant melanoma (MM) were evaluated. PATIENTS AND METHODS: The new whole-brain radiotherapy (WBRT)-30-MM was created in homogeneously treated patients receiving 10×3 Gy of WBRT for cerebral metastases from MM. It consisted of three groups with significantly different 6-month survival rates of 0% (3-5 points), 30% (7 points) and 52% (9 points) (p=0.001). The WBRT-30-MM was compared to three other scores created for cerebral metastases from MM, including first updated DS-GPA classification, Dziggel-Score and Sehmisch-Score. RESULTS: Positive predictive values (PPVs) for predicting death ≤6 months after WBRT were 100% (WBRT-30-MM), 77% (DS-GPA), 69% (Dziggel-Score) and 73% (Sehmisch-Score). PPVs for predicting survival ≥6 months were 52%, 38%, 63% and 75%, respectively. CONCLUSION: WBRT-30-MM was the most accurate instrument for predicting death ≤6 months. For predicting survival ≥6 months, Sehmisch-Score was most accurate, although all existing scorring systems appeared suboptimal for this purpose.

A new instrument for predicting survival of patients with cerebral metastases from breast cancer developed in a homogeneously treated cohort.

Background Previous survival scores for breast cancer patients with cerebral metastases were developed in cohorts receiving heterogeneous treatments, which could have introduced selection biases. A new instrument (WBRT-30-BC) was created from 170 patients receiving whole-brain radiotherapy (WBRT) alone with 30 Gy in 10 fractions. Methods Characteristics showing significant associations (p < 0.05) with overall survival (OS) or a trend (p < 0.08) on multivariate analysis were used for the WBRT-30-BC. For each characteristic, 6-month OS rates were divided by 10. These scoring points were added for each patient (patient scores). The WBRT-30-BC was compared to the diagnosis- specific graded prognostic assessment (DS-GPA) classification and Rades-Score for breast cancer regarding positive predictive values (PPVs) to identify patients dying within 6 months and patients surviving at least 6 months following WBRT. Results On multivariate analysis, Karnofsky performance score (KPS) was significant (risk ratio [RR]: 2.45, p < 0.001). In addition, extra-cerebral metastatic disease (RR: 1.52, p = 0.071) and time between breast cancer diagnosis and WBRT (RR: 1.37, p = 0.070) showed a trend. Based on these three characteristics, four predictive groups were designed: 7-9, 10-12, 13-15 and 16 points. Six-month OS rates were 8%, 41%, 68% and 100% (p < 0.001). PPVs to identify patients dying within 6 months were 92% (WBRT-30-BC), 84% (DS-GPA) and 92% (Rades-Score). PPVs to identify patients surviving for at least 6 months were 100% (WBRT-30-BC), 74% (DS-GPA) and 68% (Rades-Score). Conclusions The WBRT-30-BC appeared very accurate in predicting death ≤ 6 months and survival ≥ 6 months of breast cancer patients receiving WBRT. It was superior to previous instruments in predicting survival ≥ 6 months.

Prognostic Role of Pre-Treatment Symptoms for Survival of Patients Irradiated for Brain Metastases.

BACKGROUND/AIM: For treatment of brain metastases, a patient's survival prognosis should be considered. Existing survival scores appear complex and require complete tumor staging. For many patients, a faster and simpler tool would be helpful. PATIENTS AND METHODS: This retrospective study investigated the prognostic value of the number of pre-treatment symptoms plus eight other factors on survival of patients irradiated for brain metastases. Other factors included whole-brain radiotherapy (WBRT) regimen, age, gender, performance score, primary tumor type, number of brain metastases, extracranial metastases, and interval between cancer diagnosis and WBRT. RESULTS: The number of symptoms (p=0.002) and all other factors were significantly associated with survival on univariate analyses. On multivariate analysis, all factors but the number of symptoms (p=0.47) and primary tumor type (p=0.48) were significant. CONCLUSION: Since the number of symptoms was not an independent predictor of survival, it cannot replace existing scoring tools and may only serve for orientation.

An Instrument for Estimating the 6-Month Survival Probability After Whole-brain Irradiation Alone for Cerebral Metastases from Gynecological Cancer.

BACKGROUND/AIM: Patients with cerebral metastases from gynecological cancer who receive whole-brain irradiation (WBI) alone require personalized therapy. This study contributes to personalized care by creating an instrument to predict 6-month survival probability. PATIENTS AND METHODS: In 49 patients, six pre-treatment variables, namely age, Eastern Cooperative Oncology Group performance score (ECOG-PS), primary tumor type, number of cerebral metastases, metastasis outside the brain, and interval between diagnosis of gynecological cancer and WBI, were analyzed for survival. RESULTS: Of the six pre-treatment variables, ECOG-PS was significantly associated with survival (p=0.014) and metastasis outside the brain showed a trend for association (p=0.096). Six-month survival rates divided by 10 resulted in scores of 0, 2 or 7 points for ECOG-PS and of 2 or 7 points for metastasis outside the brain. Scores for individual patients were 2, 4, 7, 9 or 14 points. Three groups were created, those with 2-7, 9 and 14 points, with 6-month survival rates of 10%, 53% and 100%, respectively (p=0.004). CONCLUSION: An instrument was designed to predict the 6-month survival of patients receiving WBI for cerebral metastases from gynecological cancer and facilitate personalized care.

Whole-Brain Radiotherapy (WBRT) for Brain Metastases: Does the Interval Between Imaging and Treatment Matter?

BACKGROUND/AIM: Many patients with brain metastases receive whole-brain radiotherapy (WBRT). An important question is whether a delay between diagnosis of brain metastases and treatment impairs the patient's prognosis. PATIENTS AND METHODS: This retrospective study investigated the impact of the interval between diagnosis of brain metastases and WBRT plus ten additional factors on overall survival (OS) in 573 patients. Prospective trials cannot be performed due to ethical concerns. RESULTS: On univariate analyses, age (p<0.001), performance status (p<0.001), controlled primary tumor (p=0.047), metastases outside the brain (p<0.001) and completion of WBRT (p<0.001) were associated with OS. The interval between diagnosis and WBRT had no significant impact (p=0.84). On multivariate analysis, age (p=0.047), performance status (p<0.001), metastases outside the brain (p=0.029) and completion of WBRT (p<0.001) maintained significance. CONCLUSION: WBRT may be postponed for good reasons (multidisciplinary coordination of treatment, missing histology). OS was significantly associated with previously identified factors, which demonstrates consistency of the present data.

Discovery of powerful gamma-ray flares from the Crab Nebula.

The well-known Crab Nebula is at the center of the SN1054 supernova remnant. It consists of a rotationally powered pulsar interacting with a surrounding nebula through a relativistic particle wind. The emissions originating from the pulsar and nebula have been considered to be essentially stable. Here, we report the detection of strong gamma-ray (100 mega-electron volts to 10 giga-electron volts) flares observed by the AGILE satellite in September 2010 and October 2007. In both cases, the total gamma-ray flux increased by a factor of three compared with the non-flaring flux. The flare luminosity and short time scale favor an origin near the pulsar, and we discuss Chandra Observatory x-ray and Hubble Space Telescope optical follow-up observations of the nebula. Our observations challenge standard models of nebular emission and require power-law acceleration by shock-driven plasma wave turbulence within an approximately 1-day time scale.

Tissue specific methylation of c-myc in adult chickens.

Methylation of cytosine in DNA has long been correlated with modulation of specific gene expression in eukaryotes. Methylation of the c-myc locus was examined in six tissues from adult Leghorn chickens. The c-myc locus was found to be variably methylated in all examined tissues, except blood, where erythrocytic DNA showed no evidence of significant methylation of c-myc. This is contrasted with the observed sever methylation of the beta actin locus and the generally high methylation patterns found in avian erythrocytic DNA.