In vivo study of an injectable poly(acrylonitrile)-based hydrogel paste as a bulking agent for the treatment of urinary incontinence.

Urinary incontinence can be treated by endoscopic injection of bulking agents, however, no optimal therapeutic effect has been achieved upon this treatment yet. In the present study, the development of a injectable poly(acrylonitrile) hydrogel paste is described, and its efficacy and histological behavior, once injected into the submucosal space of the minipig bladder, are evaluated. A device was developed to mix poly(acrylonitrile) hydrogel powder with glycerin, used as carrier, prior to injection into the submucosal space of the bladder. Several paste deposits, depending on the size of the bladder, were injected per animal. The implants were harvested at days 7, 14, 21, 28, 84 and 168 and analyzed morphologically and by histology. The persistence of the implants was demonstrated. However, at later time points the implants were split up and surrounded by granulomatous tissue, which was gradually replaced by histiocytes and adipocytes. Transitory focal urothelial metaplasia was observed only at day 7 and moderate foreign body reaction was detected predominantly between the second and fifth week. This study demonstrated the feasibility to develop an injectable paste of poly(acrylonitrile) hydrogel thought to provide the expected bulking effect, necessary for the treatment of urinary incontinence.

Vacuum decay in quantum field theory

We study the contribution to vacuum decay in field theory due to the interaction between the long- and short-wavelength modes of the field. The field model considered consists of a scalar field of mass M with a cubic term in the potential. The dynamics of the long-wavelength modes becomes diffusive in this interaction. The diffusive behavior is described by the reduced Wigner function that characterizes the state of the long-wavelength modes. This function is obtained from the whole Wigner function by integration of the degrees of freedom of the short-wavelength modes. The dynamical equation for the reduced Wigner function becomes a kind of Fokker-Planck equation which is solved with suitable boundary conditions enforcing an initial metastable vacuum state trapped in the potential well. As a result a finite activation rate is found, even at zero temperature, for the formation of true vacuum bubbles of size M-1. This effect makes a substantial contribution to the total decay rate.

Perturbations on domain walls and strings: A covariant theory

A covariant formalism is developed for describing perturbations on vacuum domain walls and strings. The treatment applies to arbitrary domain walls in (N+1)-dimensional flat spacetime, including the case of bubbles of a true vacuum nucleating in a false vacuum. Straight strings and planar walls in de Sitter space, as well as closed strings and walls nucleating during inflation, are also considered. Perturbations are represented by a scalar field defined on the unperturbed wall or string world sheet. In a number of interesting cases, this field has a tachyonic mass and a nonminimal coupling to the world-sheet curvature.

Perturbation theory for classical thermodynamic Green's functions

A systematic time-dependent perturbation scheme for classical canonical systems is developed based on a Wick's theorem for thermal averages of time-ordered products. The occurrence of the derivatives with respect to the canonical variables noted by Martin, Siggia, and Rose implies that two types of Green's functions have to be considered, the propagator and the response function. The diagrams resulting from Wick's theorem are "double graphs" analogous to those introduced by Dyson and also by Kawasaki, in which the response-function lines form a "tree structure" completed by propagator lines. The implication of a fluctuation-dissipation theorem on the self-energies is analyzed and compared with recent results by Deker and Haake.

On the Schoenberg transformations in data analysis: theory and illustrations

The class of Schoenberg transformations, embedding Euclidean distances into higher dimensional Euclidean spaces, is presented, and derived from theorems on positive definite and conditionally negative definite matrices. Original results on the arc lengths, angles and curvature of the transformations are proposed, and visualized on artificial data sets by classical multidimensional scaling. A distance-based discriminant algorithm and a robust multidimensional centroid estimate illustrate the theory, closely connected to the Gaussian kernels of Machine Learning.

Dissipation, noise and vacuum decay in quantum field theory

We study the process of vacuum decay in quantum field theory focusing on the stochastic aspects of the interaction between long- and short-wavelength modes. This interaction results in a diffusive behavior of the reduced Wigner function describing the state of long-wavelength modes, and thereby to a finite activation rate even at zero temperature. This effect can make a substantial contribution to the total decay rate.

Intratympanic application of an antiviral agent for the treatment of Ménière's disease.

It has been suggested that Ménière's disease is part of a polyganglionitis in which symptoms result from the reactivation of neurotropic virus within the internal auditory canal, and that intratympanic applications of an antiviral agent might be an efficient therapy. In 2002, we performed a pilot study ending with encouraging results. Control of vertigo was achieved in 80% of the 17 patients included. We present here a prospective, double-blind study, with a 2-year follow-up, in 29 patients referred by ENT practitioners for a surgical treatment after failure of a medical therapy. The participation in the study was offered to patients prior to surgery. A solution of ganciclovir 50 mg/ml or of NaCl 9% was delivered for 10 consecutive days via a microwick inserted into the tympanic membrane in the direction of the round window or through a ventilation tube. One patient was withdrawn from the study immediately after the end of the injections. He could not complete the follow-up period, because of persisting vertigo. As he had received the placebo, he was then treated with the solution of ganciclovir. Symptoms persisted and he underwent a vestibular neurectomy. Among the remaining 28 patients, surgery could be postponed in 22 (81%). Surgery remained necessary to control vertigo in 3 patients from the group that received the antiviral agent, and in 3 from the control group. Using an analogical scale, patients of both groups indicated a similar improvement of their health immediately after the intratympanic injections. The scores obtained with a 36-item short-form health survey quality of life questionnaire and the Dizziness Handicap Inventory were also similar for both groups. In conclusion, most patients were improved after the intratympanic injections, but there was no obvious difference between the treated and control groups. The benefit might be due to the middle ear ventilation or reflect an improvement in the patients' emotional state.

Microstates of a neutral black hole in M theory

We consider vacuum solutions in M theory of the form of a five-dimensional Kaluza-Klein black hole cross T6. In a certain limit, these include the five-dimensional neutral rotating black hole (cross T6). From a type-IIA standpoint, these solutions carry D0 and D6 charges. We show that there is a simple D-brane description which precisely reproduces the Hawking-Bekenstein entropy in the extremal limit, even though supersymmetry is completely broken.

Systematic assessment of items influencing Crohn's disease patient's preferences in selecting an anti-TNF agent (Choose TNF trial)

Background and Aims: The three anti-TNF agents infliximab (IFX), adalimumab (ADA) andcertolizumab pegol (CZP) have demonstrated similar efficacy in induction and maintenanceof response and remission in Crohn's disease (CD) treatment. Given the comparability ofthese drugs, patient's preferences may influence the choice of the product. However, dataon patient's preferences for choosing anti-TNF agents are lacking. We therefore aimed toassess the CD patient's appraisal to select the drug of his choice and to identify factorsguiding this decision.Methods: A prospective survey among anti-TNF-naive CD patientswas performed. Patients were provided a description of the three anti-TNF agents focusingon indication, application mode (s.c. vs. i.v.), application time intervals, setting of application(hospital vs. private practice vs. patient's home), average time to apply the medication permonth, typical side effects, and the scientific evidence of efficacy and safety available for everydrug. Patients answered a questionnaire consisting of 17 questions, covering demographic,disease-specific, and medication data.Results: Hundred patients (47f/53m, mean age 45±16years) completed the questionnaire. Disease duration was <1year in 7%, 1-5 years in 31%,and >5 years in 62% of patients. Disease location was ileal in 33%, colonic in 40%, andileocolonic in 27%. Disease phenotype was inflammatory in 68%, stenosing in 29%, andinternally fistulizing in 3% of patients. Additionally, 20% had perianal fistulizing disease.Patients were already treated with the following drugs: mesalamines 61%, budesonide 44%,prednisone 97%, thiopurines 78%, methotrexate 16%. In total, 30% had already heardabout IFX, 20% about ADA, and 11% about CZP. Thirty-six percent voted for treatmentwith ADA, 28% for CZP, and 25% for IFX, whereas 11% were undecided. The followingfactors influenced the patient's decision for choosing a specific anti-TNF drug (severalanswers possible): side effects 76%, physician's recommendation 66%, application mode54%, efficacy experience 52%, time to spend for therapy 27%, patient's recommendations21%, interactions with other medications 12%. The single most important factor for choosinga specific anti-TNF was (1 answer): side effect profile 35%, physician's recommendation22%, efficacy experience 21%, application mode 13%, patient's recommendations 5%, timespent for therapy 3%, interaction with other medications 1%.Conclusions: The majority ofpatients preferred anti-TNF syringes to infusions. The safety profile of the drugs and thephysician's recommendation are major factors influencing the patient's choice for a specificanti-TNF drug. Patient's issues about safety and lifestyle habits should be taken into accountwhen prescribing specific anti-TNF formulations.

Self-dynamic structure factor of dense liquids: Theory and simulation

The self-intermediate dynamic structure factor Fs(k,t) of liquid lithium near the melting temperature is calculated by molecular dynamics. The results are compared with the predictions of several theoretical approaches, paying special attention to the Lovesey model and the Wahnstrm and Sjgren mode-coupling theory. To this end the results for the Fs(k,t) second memory function predicted by both models are compared with the ones calculated from the simulations.

A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma (NCT00516412). DESIGN AND METHODS: Eligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints. RESULTS: Thirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade ≥ 3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8-37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8-8.2) overall and 17.0 (6.4-23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood. CONCLUSIONS: Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted.

Quantitative Assessment of Soil Physical Quality in Northern China Based on S-theory

ABSTRACT Quantitative assessment of soil physical quality is of great importance for eco-environmental pollution and soil quality studies. In this paper, based on the S-theory, data from 16 collection sites in the Haihe River Basin in northern China were used, and the effects of soil particle size distribution and bulk density on three important indices of theS-theory were investigated on a regional scale. The relationships between unsaturated hydraulic conductivityKi at the inflection point and S values (S/hi) were also studied using two different types of fitting equations. The results showed that the polynomial equation was better than the linear equation for describing the relationships between -log Ki and -logS, and -log Kiand -log (S/hi)2; and clay content was the most important factor affecting the soil physical quality index (S). The variation in the S index according to soil clay content was able to be fitted using a double-linear-line approach, with decrease in the S index being much faster for clay content less than 20 %. In contrast, the bulk density index was found to be less important than clay content. The average S index was 0.077, indicating that soil physical quality in the Haihe River Basin was good.

Genome sequencing of the plant pathogen Taphrina deformans, the causal agent of peach leaf curl.

Taphrina deformans is a fungus responsible for peach leaf curl, an important plant disease. It is phylogenetically assigned to the Taphrinomycotina subphylum, which includes the fission yeast and the mammalian pathogens of the genus Pneumocystis. We describe here the genome of T. deformans in the light of its dual plant-saprophytic/plant-parasitic lifestyle. The 13.3-Mb genome contains few identifiable repeated elements (ca. 1.5%) and a relatively high GC content (49.5%). A total of 5,735 protein-coding genes were identified, among which 83% share similarities with other fungi. Adaptation to the plant host seems reflected in the genome, since the genome carries genes involved in plant cell wall degradation (e.g., cellulases and cutinases), secondary metabolism, the hallmark glyoxylate cycle, detoxification, and sterol biosynthesis, as well as genes involved in the biosynthesis of plant hormones. Genes involved in lipid metabolism may play a role in its virulence. Several locus candidates for putative MAT cassettes and sex-related genes akin to those of Schizosaccharomyces pombe were identified. A mating-type-switching mechanism similar to that found in ascomycetous yeasts could be in effect. Taken together, the findings are consistent with the alternate saprophytic and parasitic-pathogenic lifestyles of T. deformans. IMPORTANCE: Peach leaf curl is an important plant disease which causes significant losses of fruit production. We report here the genome sequence of the causative agent of the disease, the fungus Taphrina deformans. The genome carries characteristic genes that are important for the plant infection process. These include (i) proteases that allow degradation of the plant tissues; (ii) secondary metabolites which are products favoring interaction of the fungus with the environment, including the host; (iii) hormones that are responsible for the symptom of severely distorted leaves on the host; and (iv) drug detoxification enzymes that confer resistance to fungicides. The availability of the genome allows the design of new drug targets as well as the elaboration of specific management strategies to fight the disease.

Statistical mechanical theory of an oscillating isolated system: The relaxation to equilibrium

In this Contribution we show that a suitably defined nonequilibrium entropy of an N-body isolated system is not a constant of the motion, in general, and its variation is bounded, the bounds determined by the thermodynamic entropy, i.e., the equilibrium entropy. We define the nonequilibrium entropy as a convex functional of the set of n-particle reduced distribution functions (n ? N) generalizing the Gibbs fine-grained entropy formula. Additionally, as a consequence of our microscopic analysis we find that this nonequilibrium entropy behaves as a free entropic oscillator. In the approach to the equilibrium regime, we find relaxation equations of the Fokker-Planck type, particularly for the one-particle distribution function.