Cilengitide: an RGD pentapeptide ανβ3 and ανβ5 integrin inhibitor in development for glioblastoma and other malignancies

Cilengitide, a cyclicized arginine-glycine-aspartic acid-containing pentapeptide, potently blocks ανβ3 and ανβ5 integrin activation. Integrins are upregulated in many malignancies and mediate a wide variety of tumor-stroma interactions. Cilengitide and other integrin-targeting therapeutics have preclinical activity against many cancer subtypes including glioblastoma (GBM), the most common and deadliest CNS tumor. Cilengitide is active against orthotopic GBM xenografts and can augment radiotherapy and chemotherapy in these models. In Phase I and II GBM trials, cilengitide and the combination of cilengitide with standard temozolomide and radiation demonstrate consistent antitumor activity and a favorable safety profile. Cilengitide is currently under evaluation in a pivotal, randomized Phase III study (Cilengitide in Combination With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma Phase III Randomized Clinical Trial [CENTRIC]) for newly diagnosed GBM. In addition, randomized controlled Phase II studies with cilengitide are ongoing for non-small-cell lung cancer and squamous cell carcinoma of the head and neck. Cilengitide is the first integrin inhibitor in clinical Phase III development for oncology

Qualität des Weidefutters in der ökologischen Milchviehhaltung

Grazing of dairy cows is mandatory in organic farming. However, as in conventional farming there is a tendency to increase milk yield per cows by employing other feeding strategies than grazing. On-farm research was initiated on organic dairy farms in Lower Saxony to investigate the current practice of grassland utilization and dairy husbandry and to explore the potential of grazing for milk production. The results show that with an increased focus on grazing of dairy cows there is considerable room for more milk being produced from grazed grass. An in-depth analysis of the spatio-temporal pattern of the quality of the herbage on offer revealed steadily high net energy and protein concentrations almost irrespective of the sward botanical composition and the season of sampling. Research is needed to improve grazing management strategies in organic farming to make better use of the high potential of grazed grasslands and thereby increase the sustainability of milk production

Public-policy responsibilities in a restructured electricity industry

In this report, we identify and define the key public-policy values, objectives, and actions that the US electricity industry currently meets. We also discuss the opportunities for meeting these objectives in a restructured industry that relies primarily on market forces rather than on government mandates. And we discuss those functions that governments might undertake, presumably because they will not be fully met by a restructured industry on its own. These discussions are based on a variety of inputs. The most important inputs came from participants in an April 1995 workshop on Public-Policy Responsibilities and Electric Industry Restructuring: Shaping the Research Agenda. Other sources of information and insights include the reviews of a draft of this report by workshop participants and others and the rapidly growing literature on electric-industry restructuring and its implications. One of the major concerns about the future of the electricity industry is the fate of numerous social and environmental programs supported by today`s electric utilities. Many people worry that a market-driven industry may not meet the public-policy objectives that electric utilities have met in the past. Examples of potentially at-risk programs include demand-side management (DSM), renewable energy, low-income weatherization, and fuel diversity. Workshop participants represented electric utilities, public utility commissions (PUCs), state energy offices, public-interest groups, other energy providers, and the research community

Cervicothoracic Intradural Arachnoid Cyst Misdiagnosed as Motor Neuron Disease

Recognizing syndromes which mimic ALS is crucial both to avoid giving this diagnosis erroneously and since there may be appropriate treatments. We report a 63-year-old woman diagnosed with possible ALS five years ago based on upper and lower motor neuron signs with typical electrophysiology and normal cranial MRI. At reassessment, spinal MRI revealed a cervicothoracic cyst with cord compression that was successfully treated neurosurgically. Histopathology confirmed an arachnoid origin as suspected from MRI. Spinal cysts may mimic ALS and need to be thoroughly excluded by appropriate imaging

P33. Expression of alpha v beta 3 integrin in patients with high and low grade glioma

Fuente Fuente, Carlos;Puig-Pey, J.;Buenaño Pastor, Manue

A Life Cycle Analysis System to Support D and D, Pollution Prevention, and Asset Recovery

This paper describes a life cycle analysis system (LCAS) developed to support US Department of Energy (DOE) decision-making regarding deactivation and decommissioning (D and D), pollution prevention (P2), and asset recovery, and its deployment to analyze the disposition of facilities and capital assets. Originally developed for use at the Oak Ridge East Tennessee Technology Park, this approach has been refined through application at Ohio Operations Office sites and is now being deployed at a number of DOE sites. Programs such as National Metals Recycle, the D and D Focus Area, P2, and Asset Utilization are successfully using the system to make better decisions resulting in lower cost to the taxpayer and improved environmental quality. The LCAS consists of a user-friendly, cost-effective, and analytically-sound decision-aiding process and a complementary suite of automated tools to handle data administration and multiple criteria life cycle analysis (LCA). LCA is a systematic and comprehensive process for identifying, assessing, and comparing alternatives for D and D, P2, and asset recovery at government sites, and for selecting and documenting a preferred alternative. An LCA includes all of the impacts (benefits and costs) that result from a course of action over the entire period of time affected by the action. The system also includes visualizations that aid communication and help make decision-making transparent. The LCAS has three major components related to data collection, decision alternative assessment, and making the decisions. Each component is discussed in-depth using the example of deployment of the LCAS to support asset recovery

Persistence of the impact of the Hood River Conservation Project on typical and peak loads three years after weatherization

The Hood River Conservation Project (HRCP) was a major residential retrofit demonstration project, operated by Pacific Power & Light Company (Pacific Power) between 1984 and 1988, and funded by the Bonneville Power Administration (Bonneville). The project was designed to install as many cost-effective retrofit measures in as many electrically heated homes as possible in the community of Hood River, Oregon. The Pacific Power HRCP planners statistically selected a special group of 320 Hood River homes that represented a cross-section of the community. The end-use loads (electric space heating, electric water heating, and woodfuel space heating) and the interior temperatures of these homes were monitored for one year before weatherization and three years after weatherization. After more than four years of submetered data collection, 220 single-family, detached homes were available for analysis in the second load study. Weather was normalized for the four heating seasons by matching one day from the pre-program year with one day from each postretrofit year

Early treatment of complex located pediatric low-grade gliomas using iodine-125 brachytherapy alone or in combination with microsurgery

To analyze efficacy, functional outcome, and treatment toxicity of low-dose rate I-125 brachytherapy (SBT) alone or in combination with best safe resection (in case of larger tumor volumes) as first-line treatment for pediatric low-grade gliomas (PLGGs) not suitable for complete resection. Consecutively treated (2000-2014) complex located circumscribed WHO grade I/II PLGGs were included. For small tumors (4cm in diameter) SBT alone was performed;for larger tumors best safe resection and subsequent SBT was chosen. Temporary Iodine-125 seeds were used (median reference dose: 54Gy). Treatment response was estimated with the modified MacDonald criteria. Analysis of functional outcome included ophthalmological, endocrinological and neurological evaluation. Survival was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models. Toxicity was categorized according to the Common Terminology Criteria for Adverse Events. Fifty-eight patients were included treated either with SBT alone (n=39) or with SBT plus microsurgery (n=19). Five-year progression-free survival was 87%. Two patients had died due to tumor progression. Among survivors, improvement/stabilization/deterioration of functional deficits was seen in 20/14/5 patients, respectively. Complete/partial response had beneficial impact on functional scores (P=0.02). The 5-year estimated risk to receive adjuvant radiotherapy/chemotherapy was 5.2%. The overall early (delayed) toxicity rate was 8.6% (10.3%), respectively. No permanent morbidity occurred. In complex located PLGGs, early SBT alone or combined with best safe resection preserves/improves functional scores and results in tumor control rates usually achieved with complete resection. Long-term analysis is necessary for confirmation of these results

Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy†

Background This prospective multicenter study assessed the prognostic influence of the extent of resection when compared with biopsy only in a contemporary patient population with newly diagnosed glioblastoma. Patients and methods Histology, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and clinical data were centrally analyzed. Survival analyses were carried out with the Kaplan-Meier method. Prognostic factors were assessed with proportional hazard models. Results Of 345 patients, 273 underwent open tumor resection and 72 biopsies; 125 patients had gross total resections (GTRs) and 148, incomplete resections. Surgery-related morbidity was lower after biopsy (1.4% versus 12.1%, P = 0.007). 64.3% of patients received radiotherapy and chemotherapy (RT plus CT), 20.0% RT alone, 4.3% CT alone, and 11.3% best supportive care as an initial treatment. Patients ≤60 years with a Karnofsky performance score (KPS) of ≥90 were more likely to receive RT plus CT (P < 0.01). Median overall survival (OS) (progression free survival; PFS) ranged from 33.2 months (15 months) for patients with MGMT-methylated tumors after GTR and RT plus CT to 3.0 months (2.4 months) for biopsied patients receiving supportive care only. Favorable prognostic factors in multivariate analyses for OS were age ≤60 years [hazard ratio (HR) = 0.52; P < 0.001], preoperative KPS of ≥80 (HR = 0.55; P < 0.001), GTR (HR = 0.60; P = 0.003), MGMT promoter methylation (HR = 0.44; P < 0.001), and RT plus CT (HR = 0.18, P < 0.001); patients undergoing incomplete resection did not better than those receiving biopsy only (HR = 0.85; P = 0.31). Conclusions The value of incomplete resection remains questionable. If GTR cannot be safely achieved, biopsy only might be used as an alternative surgical strateg

The Life Cycle Analysis Toolbox

The life cycle analysis toolbox is a valuable integration of decision-making tools and supporting materials developed by Oak Ridge National Laboratory (ORNL) to help Department of Energy managers improve environmental quality, reduce costs, and minimize risk. The toolbox provides decision-makers access to a wide variety of proven tools for pollution prevention (P2) and waste minimization (WMin), as well as ORNL expertise to select from this toolbox exactly the right tool to solve any given P2/WMin problem. The central element of the toolbox is a multiple criteria approach to life cycle analysis developed specifically to aid P2/WMin decision-making. ORNL has developed numerous tools that support this life cycle analysis approach. Tools are available to help model P2/WMin processes, estimate human health risks, estimate costs, and represent and manipulate uncertainties. Tools are available to help document P2/WMin decision-making and implement programs. Tools are also available to help track potential future environmental regulations that could impact P2/WMin programs and current regulations that must be followed. An Internet-site will provide broad access to the tools