New automated observation systems for use in passenger aircraft to measure atmospheric carbon dioxide (CO 2 ) and other trace species have been developed and are described in this paper. The Continuous CO 2 Measuring Equipment (CME) is composed mainly of a nondispersive infrared analyzer, a datalogger, and two calibration cylinders for in situ CO 2 measurements. The Automatic Air Sampling Equipment (ASE), on the other hand, is designed for flask sampling; the instrument, connected to a metal bellows pump, is made up of a specially designed control board and can accommodate 12 flasks. The CME platform can be used to conduct high-frequency measurements of CO 2 for obtaining a detailed spatial observation over a wide area, while ASE, despite the limited flight frequency, can provide useful distributions not only of CO 2 but also various trace gas species, as well as their isotopic ratios. ASE and CME are installed on the racks in the forward cargo compartment of the aircraft and the air bypass intake is mounted on the airconditioning duct upstream of the recirculation fan. Both sets of sampling equipment are automatically controlled through input of relevant flight parameters from the aircraft data system. Their deployment in a Boeing 747-400 aircraft was approved by the aviation regulatory agencies in the United States and Japan through issuance of the supplemental type certificate (STC), while the approval for installation of CME in a Boeing 777-200ER was also obtained via STC. First measurement results of CO 2 variations obtained by CME and ASE deployed on Japan Airlines (JAL) aircraft are reported herein.

Expression levels of estrogen receptor (ER) A govern estrogendependent growth, response to endocrine therapy, and prognosis in ERA-positive breast cancer. Multiple mechanisms involved in altering ERA gene expression in breast cancer have been identified, including ERA gene amplification as well as transcriptional silencing by DNA methylation of CpG islands within the ERA promoter and mutations within the open reading frame of ERA. However, expression levels of ERA in breast cancer tissues differ widely among patients, and frequently change during disease progression and in response to systemic therapies. Recent evidence has shown that microRNA mutations or misexpression correlate with various human cancers, and miR-206 is reported to decrease endogenous ERA mRNA and protein levels in human MCF-7 breast cancer cells via two specific target sites within the 3 ¶-untranslated region of the human ERA transcript. In this study, we show for the first time that miR-206 expression is markedly decreased in ERA-positive human breast cancer tissues assayed by quantitative reverse transcription-PCR analysis. Moreover, we observe that miR-206 expression is inversely correlated with ERA but not ERB mRNA expression in breast cancer tissues. Transfection experiments revealed that introduction of miR-206 into estrogen-dependent MCF-7 breast cancer cells inhibits cell growth in a dose-and timedependent manner. Our results suggest that miR-206 could be a novel candidate for endocrine therapy that targets only ERA in breast cancer. [Cancer Res 2008;68(13):5004-8]

To define prognostic factors for breast cancer patients with brain metastases, compare their clinical courses and prognoses according to breast cancer subtypes, and analyze the causes of death in such patients. We retrospectively analyzed 1,466 patients diagnosed with brain metastases between April 1, 2001 and December 31, 2012, from 24 institutions of the Japan Clinical Oncology Group. Overall, 1,256 patients with brain metastases were included. The median overall survival (OS) was 8.7 months (95 % confidence interval [CI] 7.8-9.6 months). Univariate and multivariate analyses revealed that patients diagnosed with brain metastasis within 6 months of metastatic breast cancer diagnoses, asymptomatic brain disease, or HER2-positive/estrogen receptor-positive tumors had increased OS. Median OS after the development of brain metastases was 9.3 months (95 % CI 7.2-11.3) for the luminal type, 16.5 months (95 % CI 11.9-21.1) for the luminal-HER2 type, 11.5 months (95 % CI 9.1-13.8) for the HER2 type, and 4.9 months (95 % CI 3.9-5.9) for the triple-negative type. Luminal-HER2 type patients had significantly longer OS than patients with the luminal type (hazard ratio [HR] = 1.50, P < 0.0001) and triple-negative type (HR = 1.97, P < 0.0001); no significant differences were noted compared to HER2-type patients (HR = 1.19, P = 0.117). The prognosis and clinical course of patients with brain metastasis from breast cancer before and after developing brain metastases vary according to subtype. Focusing on the subtypes of breast cancer can optimize the prevention, early detection, and improved treatment of brain metastases.

Endocrine therapy has become the most important treatment option for women with estrogen receptor (ER)-positive breast cancer. Urgently needed are prognostic assays that can identify those who need additional adjuvant therapy, such as signal transduction inhibitors or chemotherapy, for ER-positive early breast cancer. We examined phosphorylation of ERa serine (Ser) 118, ERa Ser167, p44/42 mitogen-activated protein kinase (MAPK), and Akt and expression of progesterone receptor, amplified in breast cancer 1 (AIB1), human epidermal growth factor receptor 2 (HER2), p53, and Ki67 in ER-positive breast cancers by immunohistochemistry, and analyzed their significance for prognosis. Phosphorylation levels of ERa Ser118, ERa Ser167, MAPK, and Akt were positively correlated. AIB1 expression was significantly associated with phosphorylation of ERa Ser118, MAPK, and Akt, and HER2 expression. Low phosphorylation of ERa Ser118 and high phosphorylation of ERa Ser167 were associated with significantly improved disease-free (PZ0.0003 and PZ0.0002 respectively) and overall survival (PZ0.0007 and PZ0.0016 respectively) in multivariate analyses. Our data suggest that phosphorylation of ERa Ser118 and ERa Ser167 affects survival in ER-positive breast cancer and could be helpful in distinguishing patients who are likely to benefit from endocrine therapy alone from those who are not.

BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.