Convexity properties, moment inequalities and asymptotic exponential approximations for delay distributions in G1/G/1 systems

Pollaczek distributions pervade the class of delay distibutions in G1/G/1 systems with concave service time distributions. When the service time distribution has finite support and the delay distribution is absolutely continuous on (0, [infinity]), one can find a distribution with a pure exponential tail that satisfies the corresponding Wiener-Hopf integral equation except for values of the argument that belong to the support in question or to a translate thereof. Again for an exponentially decaying delay distribution, one can formulate sufficient moment inequalities which ensure the existence of asymptotic upper and lower bounds derived from M/D/1 and M/M/1 delay distributions which agree with the former in terms of the first two moments.waiting time Wiener-Hopf equation queueing inequalities compound geometric distribution exponential approximation

Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial

International audienceBackgroundT‐type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T‐type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain.MethodsThis proof‐of‐concept, multicentre, double‐blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add‐on therapy) to an inactive control (IC) in 114 patients with non‐diabetic peripheral neuropathic pain. After a 7‐day run‐in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention‐to‐treat population. This study is registered with EudraCT (2013‐004801‐26) and ClinicalTrials.gov (NCT02100046).ResultsThe study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per‐protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI −25.8; −5.4) from baseline compared to IC (−7.8%, 95% CI −14.3; −1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients.ConclusionEthosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events.SignificanceThis article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per‐protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T‐type calcium channel inhibition for the treatment of neuropathic pain

Galectin-inhibitory thiodigalactoside ester derivatives have antimigratory effects in cultured lung and prostate cancer cells.

Aromatic 3,3'-diesters of thiodigalactoside were synthesized in a rapid three-step sequence from commercially available thiodigalactoside and evaluated as inhibitors of cancer- and immunity-related galectins. For each of galectins-1, -3, -7, and -9N-terminal domain, aromatic 3,3'-diesters of thiodigalactoside were found to have affinities in the low micromolar range, which represents a 7-70 fold enhancement over thiodigalactoside itself. No significant improvement was found for galectin-8 N-terminal domain. Two of the compounds were selected for testing in cell culture and were shown to have potent antimigratory effects on human PC-3 prostate and human A549 nonsmall-cell lung cancer cells.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe