Next Generation Safeguards Initiative Workshop on Enhanced Recruiting for International Safeguards

In 2007, the National Nuclear Security Administration's Office of Nonproliferation and International Security (NA-24) completed a yearlong review of the challenges facing the international safeguards system today and over the next 25 years. The study found that without new investment in international safeguards, the U.S. safeguards technology base, and our ability to support International Atomic Energy Agency (IAEA) safeguards, will continue to erode and soon may be at risk. To reverse this trend, the then U.S. Secretary of Energy, Samuel Bodman, announced at the 2007 IAEA General Conference that the Department of Energy (DOE) would launch the Next Generation Safeguards Initiative (NGSI). He stated 'IAEA safeguards must be robust and capable of addressing proliferation threats. Full confidence in IAEA safeguards is essential for nuclear power to grow safely and securely. To this end, the U.S. Department of Energy will seek to ensure that modern technology, the best scientific expertise, and adequate resources are available to keep pace with expanding IAEA responsibilities.' To meet this goal, the NGSI objectives include the recruitment of international safeguards experts to work at the U.S. national laboratories and to serve at the IAEA's headquarters. Part of the latter effort will involve enhancing our existing efforts to place well-qualified Americans in a sufficient number of key safeguards positions within the IAEA's Department of Safeguards. Accordingly, the International Safeguards Project Office (ISPO) at Brookhaven National Laboratory (BNL) hosted a Workshop on Enhanced Recruiting for International Safeguards (ERIS) on October 22 and 23, 2008. The ISPO used a workshop format developed earlier with Sonalysts, Inc., that was followed at the U.S. Support Program's (USSP's) technology road-mapping sessions. ISPO invited participants from the U.S. DOE, the IAEA, the U.S. national laboratories, private industry, academia, and professional societies who either are experts in international safeguards, or understand the challenges of recruiting for technical positions. The 44 participants represented eight national laboratories, four universities, three government organizations, two international organizations, two professional organizations, and three small companies. The goal of the ERIS workshop was to improve efforts to engage U.S. citizens for IAEA positions in the Department of Safeguards. The participants considered the specific challenges of recruiting professional staff, safeguards inspectors, and managers. At the workshop's conclusion, participants presented their findings to the NNSA Office of International Regimes and Agreements (NA-243). The report's major findings are summarized

Solitary skin metastasis from sarcomatoid carcinoma of the bladder: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cutaneous metastases from carcinomas of the bladder are very rare. They are related to advanced stages of the disease and have poor prognosis with low survival rates. The common treatment modality of cutaneous metastases from a primary bladder cancer is wide local excision followed by chemotherapy.</p> <p>Case presentation</p> <p>We report a case of solitary skin metastasis from a rare type of urinary bladder carcinoma in a 68 year-old Caucasian man. Urinary bladder carcinoma metastasizing to the skin is an uncommon finding despite the high incidence of this tumor. Skin metastasis generally presents in the late stages of this disease and indicates a poor outcome.</p> <p>Conclusions</p> <p>Because of the extremely aggressive malignant potential of sarcomatoid carcinomas, the indications for a transurethral resection of the bladder should be carefully assessed and suitable therapeutic strategies should be examined further.</p

Determination Of Electron Flux Spectra In A Solar Flare With An Augmented Regularization Method: Application To Rhessi Data

Kontar et al. (2004) have shown how to recover mean source electron spectra in solar flares through a physical constraint regularization analysis of the bremsstrahlung photon spectra that they produce. They emphasize the use of non-square inversion techniques, and preconditioning combined with physical properties of the spectra to achieve the most meaningful solution to the problem. Higher-order regularization techniques may be used to generate ${overline F}(E)$ forms with certain desirable properties (e.g., higher order derivatives). They further note that such analyses may be used to infer properties of the electron energy spectra at energies well above the maximum photon energy observed. In this paper we apply these techniques to data from a solar flare observed by RHESSI on 26 February, 2002. Results using different orders of regularization are presented and compared for various time intervals. Clear evidence is presented for a change in the value of the high-energy cutoff in the mean source electron spectrum with time. We also show how the construction of the injected (accelerated) electron spectrum $F_0(E_0)$ (assuming that Coulomb collisions in a cold target dominate the electron energetics) is facilitated by the use of higher-order regularization methods.Comment: 10 pages, 7 figures, accepted to Solar Physic

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study

The purpose of the study was to investigate the toxicity and efficacy of the combination of gemcitabine and docetaxel in untreated advanced urothelial carcinoma. Patients with previously untreated, locally advanced/recurrent or metastatic urothelial carcinoma stage-IV disease were eligible. Patients with Performance status: PS ECOG >3 or age >75 years or creatinine clearance <50 ml min−1 were excluded. Study treatment consisted of docetaxel 75 mg m−2 (day 8) and gemcitabine 1000 mg m−2 (days 1+8), every 21 days for a total of six to nine cycles. A total of 31 patients with urothelial bladder cancer, 25 men and six women, aged 42–74 (median 64) years were enrolled. The majority of patients had a good PS (51.6%; PS 0). In all, 15 (48.3%) patients had locally advanced or recurrent disease only and 16 (54.8%) presented with distant metastatic spread, with multiple site involvement in 22.5%. Toxicity was primarily haematologic, and the most frequent grade 3–4 toxicities were anaemia 11 (6.7%) thrombocytopenia eight (4.9%), and neutropenia 45 (27.6%), with 10 (6.1%) episodes of febrile neutropenia. No toxic deaths occurred. A number of patients had some cardiovascular morbidity (38.7%). Nonhaematological toxicities except alopecia (29 patients) were mild. Overall response rate was 51.6%, including four complete responses (12.9%) and 12 partial responses (38.7%), while a further five patients had disease stabilisation (s.d. 16.1%). The median time to progression was 8 months (95% CI 5.1–9.2 months) and the median overall survival was 15 months (95% CI 11.2–18.5 months), with 1-year survival rate of 60%. In conclusion, this schedule of gemcitabine and docetaxel is very active and well tolerated as a first-line treatment for advanced/relapsing or metastatic urothelial carcinoma. Although its relative efficacy and tolerance as compared to classic MVAC should be assessed in a phase III setting, the favourable toxicity profile of this regimen may offer an interesting alternative, particularly in patients with compromised renal function or cardiovascular disease

Next Generation Safeguards Initiative Workshop on Enhanced Recruiting for International Safeguards

Brookhaven National Laboratory (BNL) hosted a Workshop on Enhanced Recruiting for International Safeguards October 22 and 23, 2008. The workshop was sponsored by DOE/NA-243 under the Next Generation Safeguards Initiative (NGSI). Placing well-qualified Americans in sufficient number and in key safeguards positions within the International Atomic Energy Agency’s (IAEA’s) Department of Safeguards is an important U.S. non-proliferation objective. The goal of the NGSI Workshop on Enhanced Recruiting for International Safeguards was to improve U.S. efforts to recruit U.S. citizens for IAEA positions in the Department of Safeguards. The participants considered the specific challenges of recruiting professional staff, safeguards inspectors, and managers. BNL’s International Safeguards Project Office invited participants from the U.S. Department of Energy, the IAEA, U.S. national laboratories, private industry, academia, and professional societies who are either experts in international safeguards or who understand the challenges of recruiting for technical positions. A final report for the workshop will be finalized and distributed in early 2009. The main finding of the workshop was the need for an integrated recruitment plan to take into account pools of potential candidates, various government and private agency stakeholders, the needs of the IAEA, and the NGSI human capital development plan. There were numerous findings related to and recommendations for maximizing the placement of U.S. experts in IAEA Safeguards positions. The workshop participants offered many ideas for increasing the pool of candidates and increasing the placement rate. This paper will provide details on these findings and recommendation

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/mm2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P \u3c .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned

Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer

A multicentre phase II trial was undertaken to evaluate the activity and toxicity of docetaxel plus cisplatin as first-line chemotherapy in patients with urothelial cancer. Thirty-eight patients with locally advanced or metastatic transitional-cell carcinoma of the bladder, renal pelvis or ureter received the combination of docetaxel 75 mg m−2 and cisplatin 75 mg m−2 on day 1 and repeated every 21 days, to a maximum of six cycles. The median delivered dose-intensity was 98% (range 79–102%) of the planned dose for both drugs. There were seven complete responses and 15 partial responses, for and overall response rate of 58% (95% CI, 41–74%). Responses were even seen in three patients with hepatic metastases. The median time to progression was 6.9 months, and the median overall survival was 10.4 months. Two patients who achieved CR status remain free of disease at 4 and 3 years respectively. Grade 3–4 granulocytopenia occurred in 27 patients, resulting in five episodes of febrile neutropenia. There was one toxic death in a patient with grade 4 granulocytopenia who developed acute abdomen. Grade 3–4 thrombocytopenia was rare (one patient). Other grade 3–4 toxicities observed were anaemia (three patients), vomiting (five patients), diarrhoea (four patients), peripheral neuropathy (two patients) and non-neutropenic infections (seven patients). Docetaxel plus cisplatin is an effective and well-tolerated regimen for the treatment of advanced urothelial cancer, and warrants further investigation

A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC) of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium.</p> <p>Methods</p> <p>Patients with advanced TCC were treated with gemcitabine 1200 mg/m²on days 1 and 8 and carboplatin area under the concentration-time curve(AUC) 5 on day 1 every 21 days.</p> <p>Results</p> <p>Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1–6) was administered. Overall response rate was 46.2% (95% confidence interval: 32–65%) including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6–8.4 months) and 13.6 months (95% confidence interval: 10.2–17.0 months), respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4%) patients.</p> <p>Conclusion</p> <p>The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens.</p> <p>Trial registration</p> <p>ISRCTN88259320</p

Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence

Activation of the endothelin A receptor (ETA) by endothelin-1 (ET-1) mediates events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in tumours. Specific blockade of ETA may have anticancer effects, while retaining beneficial endothelin B receptor (ETB)-mediated effects such as apoptosis and clearance of ET-1. ZD4054 is an orally active, specific ETA antagonist in clinical development. In receptor-binding studies, ZD4054 specifically bound to ETA with high affinity; no binding was detected at ETB. In a randomised placebo-controlled trial in eight healthy volunteers, a single oral dose of ZD4054 reduced forearm vasoconstriction in response to brachial artery infusion of ET-1, thus providing clinical evidence of ETA blockade. ETB blockade was assessed in an ascending, single-dose, placebo-controlled trial in 28 volunteers. For all doses of ZD4054, mean plasma ET-1 concentrations measured at 4 and 24 h were within the placebo reference range (a rise in ET-1 would indicate ETB blockade) and there was no evidence of dose-related changes. These data confirm the specificity of ZD4054 for ETA, with no activity at ETB in a clinical or preclinical setting. As a result of this specificity, ZD4054 has the potential to block multiple ETA-induced pathological processes, while allowing beneficial ETB-mediated processes to continue, which may, in turn, lead to an effective cancer therapy