Identification and Authentication of Copper Canisters for Spent Nuclear Fuel by a Portable Ultrasonic System.

The long-term storage of nuclear-spent fuel in geological repositories has introduced the need to develop new technologies for safeguarding the fuel. Continuity of knowledge about the fuel's location must be maintained during transport of the copper canisters that contain the fuel from the encapsulation plant to the final repository. Among the possible different containment and surveillance measures are the identification and authentication of each canister. The authors propose an innovative solution for this purpose, which is based on the ultrasonic acquisition of two fingerprints: an artificial code realized by chamfers machined in the inner surface of the copper lid (identification) and a natural signature due to the weld between the lid and the tube (authentication). Several prototypes of ultrasonic acquisition devices have been developed and tested on real copper samples to validate the identification and authentication concepts. This article describes the design of a new, optimized version of the ultrasonic acquisition device. The aim of this new design is to provide a solution for the identification and authentication of copper canisters using a portable device that is cost-effective and easy to use, which does not require the presence of an inspector in the field. The mechanical design of the reader has been upgraded with the introduction of a stepper motor and a new probe holder that includes a beam splitter to acquire two fingerprints simultaneously. The new device has been tested on copper samples, both with and without chamfers, and the results are reported in this article. The implementation of the seal fingerprint acquisition device (SFAD) within the new portable acquisition system is discussed at the end of this article with the goal of improving the electronic performance of the acquisition device in the field.

Comparison of Tagging Technologies for Safeguards of Copper Canisters for Nuclear Spent Fuel.

Several countries are planning to store nuclear spent fuel in long term geological repositories, preserved by copper canisters with an iron insert. This new approach involves many challenging problems and one is to satisfy safeguards requirements: the Continuity of Knowledge (CoK) of the fuel must be kept from the encapsulation plant up to the final repository. To date, no measurement system has been suggested for a unique identification and authentication. Following the list of the most important safeguards, safety and security requirements for copper canisters identification and authentication, a review of conventional tagging technologies and measurement systems for nuclear items is reported in this paper. The aim of this study is to verify to what extent each technology could be potentially used for keeping the CoK of copper canisters. Several tagging methods are briefly described and compared, discussing advantages and disadvantages.

[Quality end of life in uremic patients: theory and practice]. / Qualità del fine vita nel paziente uremico: dalla teoria alla pratica.

The rate of fragile elderly patients affected by chronic kidney disease stage 5-5D is rapidly increasing. The decision making process regarding the start and the withdrawal of dialysis is often difficult for all those involved: patients, relatives, nephrologists and renal nurses. Therefore nephrologists and renal nurses are called to rapidly improve their theoretical and practical competence about the end-of-life care. The quality of clinical intervention and management requires a sound expertise in the ethical, legal, organizational and therapeutic aspects, not trivial nor even deductible from purely private and individual opinions nor from traditional medical practice. The present paper discusses the ethical and legal implications related to the start rather than to withdrawn from dialysis, preferring a non-dialysis medical treatment and / or palliative care. Operational aspects regarding the regional network of palliative care, the path of shared decision making process and a systematic approach to optimize medical and nursing interventions through the Liverpool Care Pathway program are discussed thereafter.

Poly(ethylene glycol)-paclitaxel-alendronate self-assembled micelles for the targeted treatment of breast cancer bone metastases.

Paclitaxel (PTX) and alendronate (ALN) are effective drugs used for the treatment of breast cancer bone metastases. Growing evidence suggests that low-dose taxanes and bisphosphonates possess anti-angiogenic properties. However, PTX is water-insoluble and toxic, even if administered at anti-angiogenic dosing schedule. Polymer conjugation of PTX will increase water-solubility and improve its pharmacokinetic profile directing it to the tumor site. We further propose to combine it with ALN for active bone targeting. We conjugated ALN and PTX with poly(ethylene glycol) (PEG) forming self-assembled micelles where PTX molecules are located at the inner core and the water-soluble ALN molecules at the outer shell. PTX-PEG-ALN micelles exhibited similar in vitro cytotoxic and anti-angiogenic activity as the free drugs. Biodistribution analysis demonstrated preferential tumor accumulation of FITC-labeled PTX-PEG-ALN micelles. Pharmacokinetic studies revealed longer t1/2 of the conjugate than free PTX. PTX-PEG-ALN micelles achieved improved efficacy and safety profiles over free PTX in syngeneic and xenogeneic mouse models of mCherry-infected mammary adenocarcinoma in the tibia, as monitored intravitally non-invasively by a fluorescence imaging system. The described data warrants the potential use of PTX-PEG-ALN as bone-targeted anticancer and anti-angiogenic therapy for breast cancer bone metastases.

Covalent conjugation of poly(ethylene glycol) to proteins and peptides: strategies and methods.

PEGylation, the covalent linking of PEG chains, has become the leading drug delivery approach for proteins. This technique initiated its first steps almost 40 years ago, and since then, a variety of methods and strategies for protein-polymer coupling have been devised. PEGylation can give a number of relevant advantages to the conjugated protein, such as an important in vivo half-life prolongation, a reduction or an abolishment of immunogenicity, and a reduction of aggregation. Furthermore, the technique has demonstrated a great degree of versatility and efficacy--not only PEG-protein conjugates have reached the commercial marketplace (with nine types of derivatives), but a PEG-aptamer and PEGylated liposomes are now also available. Most of this success is due to the development of several PEGylation strategies and to the large selection of PEGylating agents presently at hand for researchers. Nevertheless, this technique still requires a certain level of familiarity and knowledge in order to achieve a positive outcome for a PEGylation project. To draw general guidelines for conducting PEGylation studies is not always easy or even possible because such experiments often require case-by-case optimization. On the other hand, several common methods can be used as starting examples for the development of tailor-made coupling conditions. Therefore, this chapter aims to provide a basic introduction to a wide range of PEGylation procedures for those researchers who may not be familiar with this field.

Dendritic poly(ethylene glycol) bearing paclitaxel and alendronate for targeting bone neoplasms.

Poly(ethylene glycol) (PEG) is the most popular polymer for protein conjugation, but its potential as carrier of low molecular weight drugs has been limited by the intrinsic low loading, owing to its chemical structure. In fact, only the two end chain groups of PEG can be modified and exploited for drug coupling. We have demonstrated that by synthesizing a dendrimer structure at the polymer end chains, it is possible to increase the drug payload and overcome this limitation. Furthermore, this approach can be improved by using heterobifunctional PEG. These polymers allow the precise linking of two different drugs, or a drug and a targeting agent, on the same polymeric chain. Heterobifunctional PEG-dendrimers have been obtained with defined chemical structures leading to their attractive use as drug delivery systems. In fact, they offer a double benefit; first, the possibility to choose the best drug/targeting agent ratio, and second, the separation of the two functions, activity and targeting, which are coupled at the opposite polymer end chains. In this study, we investigated the role of a PEG-dendrimer, H(2)N-PEG-dendrimer-(COOH)(4), as carrier for a combination of paclitaxel (PTX) and alendronate (ALN). PTX is a potent anticancer drug that is affected by severe side effects originating from both the drug itself and its solubilizing formulation, Cremophor EL. ALN is an aminobiphosphonate used for the treatment of osteoporosis and bone metastases as well as a bone-targeting moiety. The PTX-PEG-ALN conjugate was designed to exploit active targeting by the ALN molecule and passive targeting through the enhanced permeability and retention (EPR) effect. Our conjugate demonstrated a great binding affinity to the bone mineral hydroxyapatite in vitro and an IC(50) comparable to that of the free drugs combination in human adenocarcinoma of the prostate (PC3) cells. The PTX-PEG-ALN conjugate exhibited an improved pharmacokinetic profile compared with the free drugs owed to the marked increase in their half-life. In addition, PTX-PEG-ALN could be solubilized directly in physiological solutions without the need for Cremophor EL. The data presented in this manuscript encourage further investigations on the potential of PTX-PEG-ALN as treatment for cancer bone metastases.