Tyrosine kinase inhibitors for the therapy of anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is often incurable so new therapeutic approaches are needed. Tyrosine kinases inhibitors (such as imanitib, sunitinib or sorafenib) are under evaluation for the treatment of ATC. Other vascular disrupting agents, such as combretastatin A4 phosphate, and antiangiogenic agents, such as aplidin, PTK787/ZK222584 and human VEGF monoclonal antibodies (bevacizumab, cetuximab), have been evaluated. Small-molecule adenosine triphosphate competitive inhibitors directed intracellularly at EGFRs tyrosine kinase, such as erlotinib or gefitinib, are also studied. Furthermore, new molecules have been shown to be active against ATC, such as CLM94 and CLM3. However, more research is needed to finally identify therapies able to control and to cure this disease

A Trial of a 7-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults.

BACKGROUND: Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed. METHODS: In this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A. RESULTS: From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P=0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P=0.003). CONCLUSIONS: The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731.) Copyright 2010 Massachusetts Medical Society

Induced Secretion Of Pepsin-Rich Gastric Juice In The Rat By The Crude Extract From Elaeophorbia drupifera Leaves: A Dual Pathway Mechanism

Ninety male white Wistar rats (200 - 320g) were fasted for 48 hours, and used in the experiments for the collection of gastric juice according to the method of Shay et al, 1954. The extract (2.5 - 200 mg/kg) increased the secretion of gastric juice which was low in volume but rich in pepsin concentration. The adrenergic drugs dihydroergoergotoxine (hydergine) (1.25 mg/kg) and phentolamine (1.5 mg/kg) both also increased gastric secretion, which were high in volume, titratable acidity and total acid output but low in pepsin concentration. When the extract (20 mg/kg) was given in combination with either of the two sympatholytic drugs, the pepsin concentration in the juice was richer than that evoked by either of the two drugs alone. Also, atropine-extract combination significantly (

Annual Report of the Centre for Infectious Diseases Research, Diagnostics and Screening (IDS)

Veel (ziekenhuis)laboratoria sturen het te onderzoeken materiaal van patiënten naar het Centrum Infectieziekteonderzoek, diagnostiek en screening (IDS) van het RIVM. Dit betreft vooral bijzondere diagnostiek waarvoor de laboratoria zelf geen test in huis hebben. Ook komen patiëntmaterialen binnen om te monitoren of en in welke mate bepaalde ziekteverwekkende micro-organismen voorkomen. Soms worden de ziekteverwekkers zelf ingestuurd met de vraag of IDS deze wil karakteriseren. Met de verkregen resultaten houdt het RIVM er zicht op hoe vaak en waar bepaalde micro-organismen voorkomen. Op die manier kan het RIVM snel reageren op (plotselinge) ontwikkelingen op het gebied van infectieziekten. IDS beschrijft jaarlijks de resultaten om inzenders van patiëntmaterialen inzicht te geven in wat is gedaan aan diagnostiek, screening en onderzoek naar infectieziekten. De jaarrapportage 2015 beschrijft onder andere de bijdrage van IDS aan de ebola-diagnostiek in Sierra Leone. Zeven medewerkers hielpen ter plaatse door de laboratoriumdiagnostiek uit te voeren. Verder zijn bij IDS de eerste stappen gezet om de hielprikscreening uit te breiden, en wel met de screening op Severe combined immunodeficiency (SCID). Ook wordt toegelicht hoe het komt dat het griepvaccin in 2015 onvoldoende werkte. Een deel van de onder de bevolking circulerende influenzavirussen bleek af te wijken van de virussen die in het griepvaccin waren opgenomen. Het onderzoek bij IDS bestaat er vooral uit om innovatieve laboratoriumtesten te ontwikkelen, te verbeteren en in te zetten. Dit in het belang van de openbare gezondheidszorg. Bij veel van deze onderzoeken wordt een innovatieve methode gebruikt waarmee het hele genoom van een micro-organisme in kaart kan worden gebracht (Whole Genome sequencing).Many hospital and other laboratories send their patient materials to RIVM's Centre for Infectious Diseases Research, Diagnostics and Screening (IDS) for testing, particularly if special diagnostic procedures are required for which these laboratories lack the necessary testing facilities. Patient materials are also sent to IDS in order to monitor the incidence of specific pathogenic micro-organisms. In some cases the pathogens themselves are sent to IDS for characterization. The results obtained enable RIVM to keep track of where and how frequently specific micro-organisms occur, enabling RIVM to respond rapidly to any (sudden) developments relating to infectious diseases. IDS summarizes the results of these activities in an Annual Report to provide stakeholders with insight into infectious diseases research, diagnostics and screening. The topics covered in the Annual Report for 2015 include IDS's contribution to Ebola diagnostics in Sierra Leone. Seven staff members travelled to the West African nation to provide laboratory diagnostic assistance. In addition, IDS has taken initial steps to expand its heel prick screening programme to include Severe Combined Immune Deficiency syndrome (SCID). The report also explains why the Dutch flu vaccination programme was insufficiently effective in 2015. A part of the circulating influenza viruses in the human population was found to deviate from the viruses that were included in the flu vaccine. Research at IDS is mainly focused on developing, optimizing and implementing innovative laboratory tests that can help to improve public health. Much of its research uses Whole Genome Sequencing, an innovative laboratory process that determines the complete DNA sequence of a micro-organism's genome

Electromagnetic form factor via Minkowski and Euclidean Bethe-Salpeter amplitudes

The electromagnetic form factors calculated through Euclidean Bethe-Salpeter amplitude and through the light-front wave function are compared with the one found using the Bethe-Salpeter amplitude in Minkowski space. The form factor expressed through the Euclidean Bethe-Salpeter amplitude (both within and without static approximation) considerably differs from the Minkowski one, whereas form factor found in the light-front approach is almost indistinguishable from it.Comment: 3 pages, 2 figures. Contribution to the proceedings of the 20th International Conference on Few-Body Problems in Physics (FB20), Pisa, Italy, September 10-14, 2007. To be published in "Few-Body Systems

Noncommutative BTZ Black Hole in Polar Coordinates

Based on the equivalence between the three dimensional gravity and the Chern-Simons theory, we obtain a noncommutative BTZ black hole solution as a solution of $U(1,1)\times U(1,1)$ noncommutative Chern-Simons theory using the Seiberg-Witten map. The Seiberg-Witten map is carried out in a noncommutative polar coordinates whose commutation relation is equivalent to the usual canonical commutation relation in the rectangular coordinates up to first order in the noncommutativity parameter $\theta$. The solution exhibits a characteristic of noncommutative polar coordinates in such a way that the apparent horizon and the Killing horizon coincide only in the non-rotating limit showing the effect of noncommutativity between the radial and angular coordinates.Comment: 14 pages, V2: minor changes, v3: reduced for clarification, a reference adde

Nomenclature and taxonomy of Croton glabellus L. (Euphorbiaceae), a widespread Caribbean species

The application of the names Croton glabellus, C. lucidus, and Phyllanthus glabellus has been confusing since the earliest publications that used them. After a thorough review of these publications and corresponding herbarium specimens, we clarify the nomenclatural confusion surrounding these names and their taxonomy. We identify a new name, Phyllanthus glabellus Fawc. & Rendle, that was inadvertently made. We make the new combination Croton glabellus subsp. polytrichus, and we designate lectotypes for Astrocasia tremula, Croton subsect. Astraeopsis, C. glandulifer, C. lucidus var. polytrichus, and C. spicatus.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146901/1/tax605029.pd

A near-optimal change-detection based algorithm for piecewise-stationary combinatorial semi-bandits

We investigate the piecewise-stationary combinatorial semi-bandit problem. Compared to the original combinatorial semi-bandit problem, our setting assumes the reward distributions of base arms may change in a piecewise-stationary manner at unknown time steps. We propose an algorithm, GLR-CUCB, which incorporates an efficient combinatorial semi-bandit algorithm, CUCB, with an almost parameter-free change-point detector, the Generalized Likelihood Ratio Test (GLRT). Our analysis shows that the regret of GLR-CUCB is upper bounded by O(√NKT log T), where N is the number of piecewise-stationary segments, K is the number of base arms, and T is the number of time steps. As a complement, we also derive a nearly matching regret lower bound on the order of Ω(√NKT), for both piecewise-stationary multi-armed bandits and combinatorial semi-bandits, using information-theoretic techniques and judiciously constructed piecewise-stationary bandit instances. Our lower bound is tighter than the best available regret lower bound, which is Ω(√T). Numerical experiments on both synthetic and real-world datasets demonstrate the superiority of GLR-CUCB compared to other state-of-the-art algorithms

A note on Makeev's conjectures

A counterexample is given for the Knaster-like conjecture of Makeev for functions on $S^2$. Some particular cases of another conjecture of Makeev, on inscribing a quadrangle into a smooth simple closed curve, are solved positively