Automatic Formulation of Stochastic Programs Via an Algebraic Modeling Language

This paper presents an open source tool that automatically generates the so-called deterministic equivalent in stochastic programming. The tool is based on the algebraic modeling language ampl. The user is only required to provide the deterministic version of the stochastic problem and the information on the stochastic process, either as scenarios or as a transitions-based event tre

A statistical framework for analyzing shape in a time series of random geometric objects

We introduce a new framework to analyze shape descriptors that capture the geometric features of an ensemble of point clouds. At the core of our approach is the point of view that the data arises as sampled recordings from a metric space-valued stochastic process, possibly of nonstationary nature, thereby integrating geometric data analysis into the realm of functional time series analysis. We focus on the descriptors coming from topological data analysis. Our framework allows for natural incorporation of spatial-temporal dynamics, heterogeneous sampling, and the study of convergence rates. Further, we derive complete invariants for classes of metric space-valued stochastic processes in the spirit of Gromov, and relate these invariants to so-called ball volume processes. Under mild dependence conditions, a weak invariance principle in $D([0,1]\times [0,\mathscr{R}])$ is established for sequential empirical versions of the latter, assuming the probabilistic structure possibly changes over time. Finally, we use this result to introduce novel test statistics for topological change, which are distribution free in the limit under the hypothesis of stationarity.Comment: Submission versio

Platelet-activating factor: an inflammatory mediator in the acute phase of allergic conjunctivitis in a guinea-pig model

The role of platelet-activating factor (PAF) as a mediator of increased conjunctival vascular permeability was investigated in a guinea-pig model of immediate hypersensitivity. Vascular permeability of the conjunctiva was determined by measuring the albumin content in lavage fluid (LF) after topical challenge with either PAF or ovalbumin. PAF produced a dose-dependent increase of the vascular permeability within minutes. Topical pretreatment with levocabastine, a potent histamine H1-antagonist demonstrated no effect towards the vascular permeability in response to PAF provocation. Pretreatment with eyedrops containing the specific PAF antagonist BN 52021 (1%) showed a significant inhibition of the vascular permeability (60.2%) and the clinical score (27.5%) after PAF challenge. In sensitized guinea-pigs, levocabastine showed a marked inhibition of both the vascular permeability (80.5%) and the clinical score (70%) after topical challenge with ovalbumin. BN 2021, although to a lesser extent, showed a similar effect towards the vascular permeability (26.8%) and the clinical score (28%) after antigen provocation. When BN 52021 and levocabastine were administered in combination, the vascular permeability was significantly decreased after antigen challenge in comparison with eyes pretreated with levocabastine alone. These results indicate that PAF plays a role in the acute phase of allergic conjunctivitis in the guinea-pig

Drug interactions may be important risk factors for methotrexate neurotoxicity, particularly in pediatric leukemia patients

Purpose: Methotrexate administration is associated with frequent adverse neurological events during treatment for childhood acute lymphoblastic leukemia. Here, we present evidence to support the role of common drug interactions and low vitamin B12 levels in potentiating methotrexate neurotoxicity. Methods: We review the published evidence and highlight key potential drug interactions as well as present clinical evidence of severe methotrexate neurotoxicity in conjunction with nitrous oxide anesthesia and measurements of vitamin B12 levels among pediatric leukemia patients during therapy. Results: We describe a very plausible mechanism for methotrexate neurotoxicity in pediatric leukemia patients involving reduction in methionine and consequential disruption of myelin production. We provide evidence that a number of commonly prescribed drugs in pediatric leukemia management interact with the same folate biosynthetic pathways and/or reduce functional vitamin B12 levels and hence are likely to increase the toxicity of methotrexate in these patients. We also present a brief case study supporting out hypothesis that nitrous oxide contributes to methotrexate neurotoxicity and a nutritional study, showing that patients. Conclusions: Use of nitrous oxide in pediatric leukemia patients at the same time as methotrexate use should be avoided especially as many suitable alternative anesthetic agents exist. Clinicians should consider monitoring levels of vitamin B12 in patients suspected of having methotrexate- induced neurotoxic effects

Reply: Methotrexate neurotoxicity due to drug interactions: an inadequate folinic acid effect

No abstract available

Permeability of blood-tear barrier to fluorescein and albumin after application of platelet-activating factor to the eye of the guinea pig

One of the inflammatory responses of the eye to local application of platelet-activating factor (PAF) is oedema of the conjunctiva, caused by extravasation of plasma. Aim of the study was to investigate if fluorescein would leak from the blood into the tears together with plasma protein after application of PAF to the eye. Fluorescein was given intraperitoneally 30 min prior to application of 25 μl of 0.1% solution of PAF. Thirty min after PAF the tear film was collected by washing the surface of the eye with 25 μl of phosphate buffered saline (PBS). Fluorescein in eye washings and in plasma was measured by fluorophotometry and albumin by immunodiffusion. Both fluorescein and albumin appeared in a related fashion in tears, being absent in washings of placebo-treated control eyes. Extravasation of fluorescein can be used as a measure for plasma leakage in the conjunctiva with the advantage over the Evans Blue method that the former is a non-invasive method

The Wess-Zumino term and quantum tunneling

The significance of the Wess--Zumino term in spin tunneling is explored, and a formula is established for the splitting of energy levels of a particle with large fermionic spin as an applied magnetic field is switched on.Comment: Latex, 7 page

Effects of switching to PI monotherapy on measures of lipoatrophy: meta-analysis of six randomized HIV clinical trials

Background: Switching from triple combination treatment to protease inhibitor (PI) monotherapy may prevent or reverse adverse events related to long-term nucleoside analogues. Lipoatrophy is associated with long-term use of thymidine analogues (zidovudine and stavudine). Methods: A detailed MEDLINE search was conducted to identify randomised clinical trials of triple combination treatment versus PI monotherapy. Summary results from analysis of changes in body composition (DEXA analysis) were collected: the mean change in limb fat and trunk fat to Week 48 or 96, and the percentage of patients with lipoatrophy (20% reduction from baseline in limb fat) or lipohypertrophy (20% rise from baseline in trunk fat). Results: Six randomised trials of PI monotherapy versus triple therapy with data on body composition changes, measured by DEXA scanning at baseline and Week 48 or 96, were identified: Abbott-613 (LPV/r vs ZDV/3TC/EFV, induction-maintenance trial, n=105), Monark (LPV/r vs ZDV/3TC/LPV/r, first-line trial, n=63), Kalesolo (LPV/r vs LPV/r +2NRTIs, switch trial, n=42), MONOI (DRV/r vs DRV/r + 2NRTIs, switch trial, n=156), MONARCH (DRV/r vs DRV/r + 2NRTIs, switch trial, n=30) and KRETA (LPV/r vs LPV/r + ABC/3TC, switch trial, n=74). In the meta-analysis, there were greater rises in limb fat in the PI monotherapy arms than the triple therapy arms (mean difference =277g, 95% CI=+36 to+517g, p=0.024). The percentage of patients with lipoatrophy was significantly lower in the PI monotherapy arms (4%) than the triple therapy arms (20%), (p=0.0005). There was no difference between PI monotherapy and triple therapy for mean change in trunk fat (mean difference=−73g, 95% CI = −621 to +475g, p=ns). There was also no significant difference in the risk of lipohypertrophy between the PI monotherapy arms (32%) and the triple therapy arms (27%) (p=ns). In each of the four analyses, there was no evidence for heterogeneity of treatment effects between the trials (Cochran's Q tests, p=ns for each comparison). Conclusions: In this meta-analysis, the risk of lipoatrophy was significantly lower for patients taking PI monotherapy, compared to triple therapy. There was no significant difference between the arms for lipohypertrophy. However, several of the trials included zidovudine in the control arm, which carries a higher risk of lipoatrophy than tenofovir and abacavir, which are now more widely used

Application of four dyes in gene expression analyses by microarrays

BACKGROUND: DNA microarrays are widely used in gene expression analyses. To increase throughput and minimize costs without reducing gene expression data obtained, we investigated whether four mRNA samples can be analyzed simultaneously by applying four different fluorescent dyes. RESULTS: Following tests for cross-talk of fluorescence signals, Alexa 488, Alexa 594, Cyanine 3 and Cyanine 5 were selected for hybridizations. For self-hybridizations, a single RNA sample was labelled with all dyes and hybridized on commercial cDNA arrays or on in-house spotted oligonucleotide arrays. Correlation coefficients for all combinations of dyes were above 0.9 on the cDNA array. On the oligonucleotide array they were above 0.8, except combinations with Alexa 488, which were approximately 0.5. Standard deviation of expression differences for replicate spots were similar on the cDNA array for all dye combinations, but on the oligonucleotide array combinations with Alexa 488 showed a higher variation. CONCLUSION: In conclusion, the four dyes can be used simultaneously for gene expression experiments on the tested cDNA array, but only three dyes can be used on the tested oligonucleotide array. This was confirmed by hybridizations of control with test samples, as all combinations returned similar numbers of differentially expressed genes with comparable effects on gene expression