Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats

0.01). In conclusion, the five-fold higher AUC of mesna in plasma after mesna administration and the fact that mesna is more reactive with (hydrated) cisplatin than its disulphide form BNP7787 represent a plausible explanation as to why mesna administration can reduce the antitumour activity of cisplatin. After BNP7787 administration, the distribution of BNP7787 and mesna was restricted to the kidney, which confirmed the selective protection of the kidney by BNP7787

LiveShift: mesh-pull P2P live and time-shifted video streaming

The popularity of video sharing over the Internet has increased significantly. High traffic generated by such applications at the source can be better distributed using a peer-to-peer overlay. LiveShift combines both live and on-demand video streaming -- while video is transmitted through the peer-to-peer network in a live fashion, all peers participate in distributed storage. This adds the ability to replay time-shifted streams from other peers in a distributed and scalable manner. This technical report describes an architecture, a mesh-pull protocol, and a set of policies that support the envisioned use case enable. User-focused evaluation results show its effectiveness and limits in terms of quality of experience

Phase I and pharmacokinetic study of the novel chemoprotector BNP7787 in combination with cisplatin and attempt to eliminate the hydration schedule

BNP7787 (disodium 2,2′-dithio-bis-ethane sulphonate; Tavocept™) is a novel agent developed to protect against cisplatin (cis-diammine-dichloroplatinum(II))-associated chronic toxicities. In this study, we determined the recommended dose of BNP7787 when preceding a fixed dose of cisplatin, the pharmacokinetics (PKs) and the possible reduction of saline hydration. Patients with advanced solid tumours received BNP7787 in escalating doses of 4.1–41 g m−2 as a 15-min intravenous (i.v.) infusion followed by cisplatin 75 mg m−2 as a 60-min i.v. infusion together with pre- and postcisplatin saline hydration in a volume of 2200 ml; cycles were repeated every 3 weeks. PK was carried out using BNP7787, cisplatin and the combination. Twenty-five patients were enrolled in stage I of the study to determine the recommended dose of BNP7787. No dose-limiting toxicity was reached. The highest dose level of 41 g m−2 resulted in a low incidence of grade 2 toxicities, being nausea and vomiting, dry mouth or bad taste and i.v. injection site discomfort. Doses of BNP7787 ⩾18.4 g m−2 did not show a drug interaction between BNP7787 and cisplatin. In stage II of the study, patients received a fixed dose of BNP7787 of 18.4 g m−2 preceding cisplatin and were entered in prespecified reduced saline hydration steps. A total of 21 patients in cohorts of six to nine patients received reduced saline hydration of 1600 ml (step A), 1000 ml (step B) and 500 ml (step C). In step C, two out of six evaluable patients experienced grade 1 nephrotoxicity. Cisplatin acute toxicities in all 46 patients were as expected. Only five patients complained of paresthesias grade 1 and six developed slight audiometric changes. Partial tumour response was observed in four patients and stable disease in 15 patients. In conclusion, BNP7787 was tolerated well up to doses of 41 g m−2. The recommended dose of 18.4 g m−2 enabled safe reduction of the saline hydration schedule for cisplatin to 1000 ml. Further studies will assess whether BNP7787 offers protection against platinum-related late side effects

Pain in platin-induced neuropathies: A systematic review and meta-analysis

INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment

Personality psychology: Lexical approaches, assessment methods, and trait concepts reveal only half of the story—Why it is time for a paradigm shift

This article develops a comprehensive philosophy-of-science for personality psychology that goes far beyond the scope of the lexical approaches, assessment methods, and trait concepts that currently prevail. One of the field’s most important guiding scientific assumptions, the lexical hypothesis, is analysed from meta-theoretical viewpoints to reveal that it explicitly describes two sets of phenomena that must be clearly differentiated: 1) lexical repertoires and the representations that they encode and 2) the kinds of phenomena that are represented. Thus far, personality psychologists largely explored only the former, but have seriously neglected studying the latter. Meta-theoretical analyses of these different kinds of phenomena and their distinct natures, commonalities, differences, and interrelations reveal that personality psychology’s focus on lexical approaches, assessment methods, and trait concepts entails a) erroneous meta-theoretical assumptions about what the phenomena being studied actually are, and thus how they can be analysed and interpreted, b) that contemporary personality psychology is largely based on everyday psychological knowledge, and c) a fundamental circularity in the scientific explanations used in trait psychology. These findings seriously challenge the widespread assumptions about the causal and universal status of the phenomena described by prominent personality models. The current state of knowledge about the lexical hypothesis is reviewed, and implications for personality psychology are discussed. Ten desiderata for future research are outlined to overcome the current paradigmatic fixations that are substantially hampering intellectual innovation and progress in the field

LiveShift: Peer-to-peer live streaming with distributed time-shifting

The increasing assortment of devices with IP connectivity contributes to the high popularity of video sharing over the Internet. High traffic generated by such applications at the source can be better distributed using a peer-to-peer overlay, since every user forwards information to other users. Current implementations target either live or on demand video streaming. LiveShift is an application that combines both approaches. While video is transmitted through the peer-to-peer network in a live fashion, all peers participate in a distributed storage. This adds ability to replay time-shifted streams from other peers in a distributed and scalable manner. For the demonstration, a decentralized network is used, with peers running on EMANICSLab nodes and notebook computers

Incentives for Voting-based Quality Control and Document Storage in P2P Collaboration Systems

Peer-to-peer (P2P) systems achieve scalability, fault tolerance, and load balancing, while effectively reducing infrastructure cost compared to client/server systems. For large wiki-based collaboration systems these characteristics can be beneficial as well. However, a fully decentralized P2P-based collaboration system requires appropriate incentives for users to (a) contribute resources for storing and providing documents, and (b) to participate in collaborative control mechanisms for keeping content quality at a high level. Therefore, this position paper proposes a score-based incentive scheme for voting-based quality control and document storage in a P2P-based collaboration system. The approach is based on the PeerVote mechanism, which enables users to vote on content modifications. In order to encourage peers to store and vote on documents, each peer is assigned a score related to its contribution. Peers have an incentive to achieve a high score, as only this allows them to create and approve new documents. The proposed scheme is resistant to fraud, since the score of a peer can be verified by any other peer

Mobile P2P Fast Similarity Search

In informal data sharing environments, misspellings cause problems for data indexing and retrieval. This is even more pronounced in mobile environments, in which devices with limited input devices are used. In a mobile environment, similarity search algorithms for finding misspelled data need to account for limited CPU and bandwidth. This demo shows P2P fast similarity search (P2PFastSS) running on mobile phones and laptops that is tailored to uncertain data entry and uses available resources efficiently. In this demo, users publish and search for textual content containing misspellings without relying on query logging, as done by Google, and with a minimum distributed indexing infrastructure. Similarity search is supported by using the concept of deletion neighborhood to evaluate the edit distance metric of string similarity