Re: Response to Request for Relevant Information on Bisphenol A Dear Ms. Oshita,

Authoritative Bodies Mechanism: Bisphenol-A). The Polycarbonate/BPA Global Group consists of the leading global manufacturers of bisphenol A and polycarbonate plastic, which for many years have supported and conducted scientific research to understand whether bisphenol A has the potential to cause health or environmental effects and to support scientifically sound public policy. As indicated by the signatures at the end of the attachment, the comments were prepare

Disease-specific survival for limited-stage small-cell lung cancer affected by statistical method of assessment

BACKGROUND: In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model), or log-normal survival analysis. METHODS: Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS). DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all patients using the Boag, Kaplan-Meier, Cox, and log-normal survival analysis methods. Factors with significant effects on DSS were identified with step-wise forward multivariate Cox and log-normal survival analyses. Then, DSS was ascertained for patients with specific characteristics defined by these factors. RESULTS: The median follow-up of those alive was 9.5 years. The lack of events after 1966 days precluded comparison after 5 years. DSS assessed by the four methods in the full cohort differed by 0–2% at 1 year, 0–12% at 3 years, and 0–1% at 5 years. Log-normal survival analysis indicated DSS of 38% at 3 years, 10–12% higher than with other methods; univariate 95% confidence limits were non-overlapping. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction significantly impacted DSS. DSS assessed by the Cox and log-normal survival analysis methods for four clinical risk groups differed by 1–6% at 1 year, 15–26% at 3 years, and 0–12% at 5 years; multivariate 95% confidence limits were overlapping in all instances. CONCLUSION: Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction all significantly impacted DSS. Apparent DSS for patients was influenced by the statistical methods of assessment. This would be clinically relevant in the development or improvement of clinical management strategies

Increased expression of integrin-linked kinase is associated with shorter survival in non-small cell lung cancer

BACKGROUND: Integrin-linked kinase (ILK) promotes tumor growth and invasion. Increased ILK expression is correlated with progression of several tumor types, but the expression of ILK has not been investigated in patients with non-small cell lung cancers (NSCLCs). METHODS: We investigated ILK expression in patients with NSCLC by means of immunohistochemistry. RESULTS: ILK expression was significantly associated with tumor grade, T status, lymph node metastasis and stage. (p = 0.0169 for tumor grade; p = 0.0006 for T status; p = 0.0002 for lymph node metastasis; p < 0.0001 for stage). The 5-year survival rates for patients with strong and weak or no ILK expression levels were 20% and 59%, respectively: the difference was statistically significant (p < 0.0001). A multivariate analysis of survival revealed that ILK expression, T status, N status and vascular invasion were statistically significant prognostic factors (p = 0.0218 for ILK; p = 0.0046 for T status; p < 0.0001 for N status; p < 0.0001 for vascular invasion). CONCLUSIONS: Our study demonstrates that increased expression of ILK is a poor prognostic factor in patients with NSCLC

Transmission electron microscopic observations of nanobubbles and their capture of impurities in wastewater

Unique properties of micro- and nanobubbles (MNBs), such as a high adsorption of impurities on their surface, are difficult to verify because MNBs are too small to observe directly. We thus used a transmission electron microscope (TEM) with the freeze-fractured replica method to observe oxygen (O2) MNBs in solutions. MNBs in pure water and in 1% NaCl solutions were spherical or oval. Their size distribution estimated from TEM images close to that of the original solution is measured by light-scattered methods. When we applied this technique to the observation of O2 MNBs formed in the wastewater of a sewage plant, we found the characteristic features of spherical MNBs that adsorbed surrounding impurity particles on their surface

A Novel Therapy for Melanoma Developed in Mice: Transformation of Melanoma into Dendritic Cells with Listeria monocytogenes

Listeria monocytogenes is a gram-positive bacteria and human pathogen widely used in cancer immunotherapy because of its capacity to induce a specific cytotoxic T cell response in tumours. This bacterial pathogen strongly induces innate and specific immunity with the potential to overcome tumour induced tolerance and weak immunogenicity. Here, we propose a Listeria based vaccination for melanoma based in its tropism for these tumour cells and its ability to transform in vitro and in vivo melanoma cells into matured and activated dendritic cells with competent microbicidal and antigen processing abilities. This Listeria based vaccination using low doses of the pathogen caused melanoma regression by apoptosis as well as bacterial clearance. Vaccination efficacy is LLO dependent and implies the reduction of LLO-specific CD4+ T cell responses, strong stimulation of innate pro-inflammatory immune cells and a prevalence of LLO-specific CD8+ T cells involved in tumour regression and Listeria elimination. These results support the use of low doses of pathogenic Listeria as safe melanoma therapeutic vaccines that do not require antibiotics for bacterial removal

The First Result of Global Commissioning of the ATLAS Endcap Muon Trigger System in ATLAS Cavern

We report on the ATLAS commissioning run from the view point of the Thin Gap Chamber (TGC), which is the ATLAS end cap muon trigger detector. All the TGC sectors with on-detector electronics are going to be installed to the ATLAS cavern by the end of September 2007. To integrate all sub-detectors before the physics run starting from early 2008, the global commissioning run together with other sub-detectors has been performed from June 2007. We have evaluated the performance of the complete trigger chain of the TGC electronics and provide the trigger signal using cosmic-ray to the sub-systems in the global run environment

Bcl-2 and β1-integrin predict survival in a tissue microarray of small cell lung cancer.

INTRODUCTION: Survival in small cell lung cancer (SCLC) is limited by the development of chemoresistance. Factors associated with chemoresistance in vitro have been difficult to validate in vivo. Both Bcl-2 and β(1)-integrin have been identified as in vitro chemoresistance factors in SCLC but their importance in patients remains uncertain. Tissue microarrays (TMAs) are useful to validate biomarkers but no large TMA exists for SCLC. We designed an SCLC TMA to study potential biomarkers of prognosis and then used it to clarify the role of both Bcl-2 and β(1)-integrin in SCLC. METHODS: A TMA was constructed consisting of 184 cases of SCLC and stained for expression of Bcl-2 and β(1)-integrin. The slides were scored and the role of the proteins in survival was determined using Cox regression analysis. A meta-analysis of the role of Bcl-2 expression in SCLC prognosis was performed based on published results. RESULTS: Both proteins were expressed at high levels in the SCLC cases. For Bcl-2 (n=140), the hazard ratio for death if the staining was weak in intensity was 0.55 (0.33-0.94, P=0.03) and for β(1)-integrin (n=151) was 0.60 (0.39-0.92, P=0.02). The meta-analysis showed an overall hazard ratio for low expression of Bcl-2 of 0.91(0.74-1.09). CONCLUSIONS: Both Bcl-2 and β(1)-integrin are independent prognostic factors in SCLC in this cohort although further validation is required to confirm their importance. A TMA of SCLC cases is feasible but challenging and an important tool for biomarker validation

Final Test at the Surface of the ATLAS Endcap Muon Trigger Chamber Electronics

For the detector commissioning planned in 2007, sector assembly of the ATLAS muon-endcap trigger chambers and final test at the surface for the assembled electronics are being done in CERN and almost completed. For the test, we built up the Data Acquisition (DAQ) system using test pulse of two types and cosmic rays in order to check functionality of the various aspects of the electronics mounted on a sector. So far, 99% of all 320,000 channels have been tested and most of them were installed into the ATLAS cavern. In this presentation, we will describe the DAQ systems and mass-test procedure in detail, and report the result of electronics test with some actual experience

Status of the ATLAS Level-1 Central Trigger and Muon Barrel Trigger and First Results from Cosmic-Ray Data

The ATLAS detector at CERN's Large Hadron Collider (LHC) will be exposed to proton-proton collisions from beams crossing at 40~MHz. A three-level trigger system will select potentially interesting events in order to reduce the read-out rate to about 200 Hz. The first trigger level is implemented in custom-built electronics and makes an initial fast selection based on detector data of coarse granularity. It has to reduce the rate by a factor of $10^4$ to less than 100~kHz. The other two consecutive trigger levels are in software and run on PC farms. We present an overview of the first-level central trigger and the muon barrel trigger system and report on the current installation status. Moreover, we show analysis results of cosmic-ray data recorded in situ at the ATLAS experimental site with final or close-to-final hardware

The ATLAS trigger - high-level trigger commissioning and operation during early data taking

The ATLAS experiment is one of the two general-purpose experiments due to start operation soon at the Large Hadron Collider (LHC). The LHC will collide protons at a centre of mass energy of 14~TeV, with a bunch-crossing rate of 40~MHz. The ATLAS three-level trigger will reduce this input rate to match the foreseen offline storage capability of 100-200~Hz. This paper gives an overview of the ATLAS High Level Trigger focusing on the system design and its innovative features. We then present the ATLAS trigger strategy for the initial phase of LHC exploitation. Finally, we report on the valuable experience acquired through in-situ commissioning of the system where simulated events were used to exercise the trigger chain. In particular we show critical quantities such as event processing times, measured in a large-scale HLT farm using a complex trigger menu