Safety Belt Use, Ejection and Entrapment

One in every five occupants thrown from a car receives fatal injuries. A motorist who uses a safety belt, in all probability, will not be thrown from the car during a crash. The rate of fatal injury for ejected occupants was found to be 40 times the rate for occupants not thrown from their cars, as determined from national accident sampling data. These data refute the popular notion that "being thrown clear" has survival benefit. In addition, there was no evidence that wearing a safety belt increased fatality risk from vehicle fire or submersion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67129/2/10.1177_109019818401100205.pd

Final Report: Caustic Waste-Soil Weathering Reactions and Their Impacts on Trace Contaminant Migration and Sequestration

The principal goal of this project was to assess the molecular nature and stability of radionuclide (137-Cs, 90-Sr, and 129-I) immobilization during weathering reactions in bulk Hanford sediments and their high surface area clay mineral constituents. We focused on the unique aqueous geochemical conditions that are representative of waste-impacted locations in the Hanford site vadose zone: high ionic strength, high pH and high Al concentrations. The specific objectives of the work were to (i) measure the coupling of clay mineral weathering and contaminant uptake kinetics of Cs+, Sr2+ and I-; (ii) determine the molecular structure of contaminant binding sites and their change with weathering time during and after exposure to synthetic tank waste leachate (STWL); (iii) establish the stability of neoformed weathering products and their sequestered contaminants upon exposure of the solids to more “natural” soil solutions (i.e., after removal of the caustic waste source); and (iv) integrate macroscopic, microscopic and spectroscopic data to distinguish labile from non-labile contaminant binding environments, including their dependence on system composition and weathering time. During this funding period, we completed a large set of bench-scale collaborative experiments and product characterization aimed at elucidating the coupling between mineral transformation reactions and contaminant sequestration/stabilization. Our experiments included three representative Hanford sediments: course and fine sediments collected from the Hanford Formation and Ringold Silt, in addition to investigations with specimen clay minerals illite, vermiculite, smectite and kaolinite. These experiments combined macroscopic measurements of element release, contaminant uptake and subsequent neoformed mineral dissolution behavior, with detailed studies of solid phase products using SEM and TEM microscopy, NMR, XAS and FTIR spectroscopy. Our studies have shown direct coupling between mineral transformation reactions and contaminant sequestration/stabilization

Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma is an incurable disease with an average survival of less than one year. Talabostat is a novel dipeptidyl peptidase inhibitor with immunostimulatory properties.</p> <p>Methods</p> <p>This phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75–100 mg/m²cisplatin combined with 300–400 mcg talabostat bid for 6, 21-day cycles. The primary endpoint was overall response. The rate of complete responses, duration of overall objective response, progression-free survival (PFS), and overall survival were the secondary endpoints.</p> <p>Results</p> <p>Six objective partial responses were recorded in the 74 patients (8.1%) in the intention-to-treat population. Five of these responses involved the 40 evaluable patients (12.5%). Thirty-one percent of patients reported SAEs to the combination of talabostat and cisplatin.</p> <p>Conclusion</p> <p>Acceptable tolerability was observed in the intention-to-treat population and antitumor activity was observed in 12.5% of evaluable patients, which is not greater than historical expectation with cisplatin alone.</p

Surface complexation model for strontium sorption to amorphous silica and goethite

Strontium sorption to amorphous silica and goethite was measured as a function of pH and dissolved strontium and carbonate concentrations at 25°C. Strontium sorption gradually increases from 0 to 100% from pH 6 to 10 for both phases and requires multiple outer-sphere surface complexes to fit the data. All data are modeled using the triple layer model and the site-occupancy standard state; unless stated otherwise all strontium complexes are mononuclear. Strontium sorption to amorphous silica in the presence and absence of dissolved carbonate can be fit with tetradentate Sr2+ and SrOH+ complexes on the β-plane and a monodentate Sr2+complex on the diffuse plane to account for strontium sorption at low ionic strength. Strontium sorption to goethite in the absence of dissolved carbonate can be fit with monodentate and tetradentate SrOH+ complexes and a tetradentate binuclear Sr2+ species on the β-plane. The binuclear complex is needed to account for enhanced sorption at hgh strontium surface loadings. In the presence of dissolved carbonate additional monodentate Sr2+ and SrOH+ carbonate surface complexes on the β-plane are needed to fit strontium sorption to goethite. Modeling strontium sorption as outer-sphere complexes is consistent with quantitative analysis of extended X-ray absorption fine structure (EXAFS) on selected sorption samples that show a single first shell of oxygen atoms around strontium indicating hydrated surface complexes at the amorphous silica and goethite surfaces

Shadowing in Inelastic Scattering of Muons on Carbon, Calcium and Lead at Low XBj

Nuclear shadowing is observed in the per-nucleon cross-sections of positive muons on carbon, calcium and lead as compared to deuterium. The data were taken by Fermilab experiment E665 using inelastically scattered muons of mean incident momentum 470 GeV/c. Cross-section ratios are presented in the kinematic region 0.0001 < XBj <0.56 and 0.1 < Q**2 < 80 GeVc. The data are consistent with no significant nu or Q**2 dependence at fixed XBj. As XBj decreases, the size of the shadowing effect, as well as its A dependence, are found to approach the corresponding measurements in photoproduction.Comment: 22 pages, incl. 6 figures, to be published in Z. Phys.

Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14–41%); the intent-to-treat response rate was 21% (CI 95%: 12–34%). Median time to neurologic progression was 49 days (range 1–515(+)); median survival was 88 days (range 1–515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians. © 2001 Cancer Research Campaign http://www.bjcancer.co

The Oncogenic role of miR-155 in breast cancer

miR-155 is an oncogenic miRNA with well described roles in leukemia. However, additional roles of miR-155 in breast cancer progression have recently been described. A thorough literature search was conducted to review all published data to date, examining the role of miR-155 in breast cancer. Data on all validated miR-155 target genes was collated to identify biologic pathways relevant to miR-155 and breast cancer progression. Publications describing the clinical relevance, functional characterization, and regulation of expression of miR-155 in the context of breast cancer are reviewed. A total of 147 validated miR-155 target genes were identified from the literature. Pathway analysis of these genes identified likely roles in apoptosis, differentiation, angiogenesis, proliferation, and epithelial-mesenchymal transition. The large number of validated miR-155 targets presented here provide many avenues of interest as to the clinical potential of miR-155. Further investigation of these target genes will be required to elucidate the specific mechanisms and functions of miR-155 in breast cancer. This is the first review examining the role of miR-155 in breast cancer progression. The collated data of target genes and biologic pathways of miR-155 identified in this review suggest new avenues of research for this oncogenic miRNA.Sam Mattiske, Rachel J. Suetani, Paul M. Neilsen, and David F. Calle

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

The purpose of this study is to determine the toxicity and efficacy of temozolomide (TMZ) p.o. followed by subcutaneous (s.c.) low-dose interleukin-2 (IL2), granulocyte-monocyte colony stimulating factor (GM-CSF) and interferon-alpha 2b (IFN alpha) in patients with metastatic melanoma. A total of 74 evaluable patients received, in four separate cohorts, escalating doses of TMZ (150-250 mg m(-2)) for 5 days followed by s.c. IL2 (4 MIU m(-2)), GM-CSF (2.5 microg kg(-1)) and IFN alpha (5 MIU flat) for 12 days. A second identical treatment was scheduled on day 22 and cycles were repeated in stable or responding patients following evaluation. Data were analysed after a median follow-up of 20 months (12-30 months). The overall objective response rate was 31% (23 out of 74; confidence limits 20.8-42.9%) with 5% CR. Responses occurred in all disease sites including the central nervous system (CNS). Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease. Median survival was 252 days (8.3 months), 1 year survival 41%. Thrombocytopenia was the primary toxicity of TMZ and was dose- and patient-dependent. Lymphocytopenia (grade 3-4 CTC) occurred in 48.5% (34 out of 70) fully monitored patients following TMZ and was present after immunotherapy in two patients. The main toxicity of combined immunotherapy was the flu-like syndrome (grade 3) and transient liver function disturbances (grade 2 in 20, grade 3 in 15 patients). TMZ p.o. followed by s.c. combined immunotherapy demonstrates efficacy in patients with stage IV melanoma and is associated with toxicity that is manageable on an outpatient basi

Identification and Pathway Analysis of microRNAs with No Previous Involvement in Breast Cancer

microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described