Spatially explicit exposure models: application to military sites

As a result of defense-related activities, large areas of valuable habitats can be physically disturbed and/or contaminated by hazardous pollutants. It is, however, important to understand that the military impact on such areas may not be wholly detrimental to the environment: their closure to the public can result in environmental conservation of large portions of habitat. Many former military ranges have been converted for civil usage; others are still actively operated for military purposes. In both cases, a major task for environmental policy- and decision-makers is to determine scientifically justified reuse and/or operation scenarios that would not result in deterioration of site habitats and that would in fact be favorable to further development of biodiversity within the areas' existing ecosystems. Ecological risk assessment is suggested as the key process to use in facilitating the assessment of the ecological value of contaminated and/or disturbed military sites and in the development of a reuse decision protocol. We are currently developing and integrating a number of risk and habitat assessment techniques into such a protocol. This paper presents our approach to one aspect of this system: the incorporation of spatial information into ecological risk assessment. We present a software prototype that calculates radionuclide accumulation by deer foraging in areas having specified contamination patterns.     

Public awareness and disaster risk reduction: just-in-time networks and learning

Improving public awareness through education has been recognized widely as a basis for reducing the risk of disasters. Some of the first disaster just-in-time (JIT) education modules were built within 3-6 days after the south Asia tsunami, Hurricane Katrina, and the Bam, Pakistan, and Indonesia earthquakes through a Supercourse. Web monitoring showed that visitors represented a wide spectrum of disciplines and educational levels from 120 developed and developing countries. Building disaster networks using an educational strategy seizes the opportunity of increased public interest to teach and find national and global expertise in hazard and risk information. To be effective, an expert network and a template for the delivery of JIT education must be prepared before an event occurs, focusing on developing core materials that could be customized rapidly, and then be based on the information received from a recent disaster. The recyclable process of the materials would help to improve the quality of the teaching, and decrease the time required for preparation. The core materials can be prepared for disasters resulting from events such as earthquakes, hurricanes, tsunamis, floods, and bioterrorism.     

Chronic disease epidemiology, cancer and mobile global approaches to disease prevention

The focus of this symposium was worldwide prevention of chronic disease through the use of inexpensive Internet pathways, as demonstrated with the Supercourse project, and other initiatives, including promoting mobile phone technology (m-health). This symposium highlighted the need to use the Supercourse to prevent cancer and other chronic diseases. It also highlighted several components of the Supercourse library, including the former Soviet Union network, the Latin American network, and some other initiatives.     

Selective neck dissection in node-positive squamous cell carcinoma of the head and neck

Objective The optimal type of neck dissection in head and neck squamous cell carcinoma (SCC) with clinical cervical metastases has not been determined. The following study was performed to determine the rate of regional control with selective neck dissection (SND) in these patients. Study Design Case series with planned data collection. Settings Single institution, cancer center. Methods and Subjects Patients with cervical lymph node metastases from mucosal cancers of the head and neck who were treated with SND from 2000 to 2010 were selected. Demographics, tumor characteristics, extent of neck dissection, adjuvant treatments, locoregional control, and survival were recorded. Recurrence in the neck and disease-specific survival (DSS) were primary and secondary end points. Results One hundred eight patients underwent SND. Sixty-nine (64%) were male. Median age was 62 (20-89) years. The most common primary site was the oral cavity (71.3%). Ninety-five (88%) received adjuvant treatment. Median follow-up was 21 months. Six patients (5.5%) had isolated recurrence in the dissected neck. Patients with N2C disease had poorer neck recurrence-free survival. At the end of study, 64 (59.3%) patients had no evidence of disease, and 23 (21.3%) had died of disease. Two-year DSS was 76.9%. Number of positive nodes (P = .026) and positive surgical margins (P = .001), among others, were predictors of poorer DSS. Conclusion In a highly selected group of patients with cervical lymph node metastases from head and neck SCC, selective neck dissection is effective in controlling the disease in the neck when performed in the setting of a multimodality treatment, including adjuvant radiotherapy or radiochemotherapy.     

Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma

We have previously shown that osteosarcomas (OS) have states of increased interstitial fluid pressure (IFP), which correlate with increased proliferation and chemosensitivity. In this study, we hypothesized that constitutively raised IFP in OS regulates angiogenesis. Sixteen patients with the clinical diagnosis of OS underwent blood flow and IFP readings by the wick‐in‐needle method at the time and location of open biopsy. Vascularity was determined by capillary density in the biopsy specimens. We performed digital image analysis of immunohistochemical staining for CD31, VEGF‐A, VEGF‐C, and TPA on paraffin‐embedded tissue blocks of the biopsy samples. Clinical results were validated in a pressurized cell culture system. Interstitial fluid pressures in the tumors (mean 33.5 ± SD 17.2 mmHg) were significantly higher (p = 0.00001) than that in normal tissue (2.9 ± 5.7 mmHg). Pressure readings were significantly higher in low vascularity tumors compared to high vascularity tumors (p < 0.001). In the OS cell lines, growth in a pressurized environment was associated with VEGF‐A downregulation, VEGF‐C upregulation, and TPA upregulation. The reverse was seen in the OB cell line. Growth in the HUVEC cell line was not significantly inhibited in a pressurized environment. Immunohistochemical assessment for VEGF‐A (p = 0.01), VEGF‐C (p = 0.008), and TPA (p = 0.0001) translation were consistent with the findings on PCR. Our data suggests that some molecules in angiogenesis are regulated by changes in IFP. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1520–1525, 2008     

Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma

New anticancer drugs that target oncogenic signaling molecules have greatly improved the treatment of certain cancers. However, resistance to targeted therapeutics is a major clinical problem and the redundancy of oncogenic signaling pathways provides back-up mechanisms that allow cancer cells to escape. For example, the AKT and PIM kinases produce parallel oncogenic signals and share many molecular targets, including activators of cap-dependent translation. Here, we show that PIM kinase expression can affect the clinical outcome of lymphoma chemotherapy. We observe the same in animal lymphoma models. Whereas chemoresistance caused by AKT is readily reversed with rapamycin, PIM-mediated resistance is refractory to mTORC1 inhibition. However, both PIM- and AKT-expressing lymphomas depend on cap-dependent translation, and genetic or pharmacological blockade of the translation initiation complex is highly effective against these tumors. The therapeutic effect of blocking cap-dependent translation is mediated, at least in part, by decreased production of short-lived oncoproteins including c-MYC, Cyclin D1, MCL1, and the PIM1/2 kinases themselves. Hence, targeting the convergence of oncogenic survival signals on translation initiation is an effective alternative to combinations of kinase inhibitors.     

Factors associated with Type I and Type II endometrial cancer

Objective  

We investigated risk factors for Type II (n = 176) vs. Type I (n = 1,576) endometrial cancer (EC) in cases treated at Magee-Womens Hospital between 1996 and 2008.