Equivalence and bifurcations of finite order stochastic processes

This article presents an equivalence notion of finite order stochastic processes. Local dependence measures are defined in terms of ratios of joint and marginal probability densities. The dependence measures are classified topologically using level sets. The corresponding bifurcation theory is illustrated with some simple examples

A weak bifucation theory for discrete time stochastic dynamical systems

This article presents a bifurcation theory of smooth stochastic dynamical systems that are governed by everywhere positive transition densities. The local dependence structure of the unique strictly stationary evolution of such a system can be expressed by the ratio of joint and marginal probability densities; this ‘dependence ratio’ is a geometric invariant of the system. By introducing a weak equivalence notion of these dependence ratios, we arrive at a bifurcation theory for which in the compact case, the set of stable (nonbifurcating) systems is open and dense. The theory is illustrated with some simple examples

Promoting independent learning skills using video on digital language laboratories

This is the author's PDF version of an article published in Computer assisted language learning ©2006. The definitive version is available at http://www.informaworld.com/The article discusses the potential for developing independent learning skills using the digital language laboratory with particular reference to exploiting the increasingly available resource of digital video. It investigates the potential for recording and editing video clips from online sources and digitalising clips from analogue recordings and reflects on the current status quo regarding the complex copyright regulations in this area. It describes two pilot self-access programmes based on video clips which were undertaken with University College Chester undergraduates and reflects on the value of the experience for students in developing a wide range of language skills as well as independent learning skills using their feedback on the experience

More hedging instruments may destabilize markets

This paper formalizes the idea that more hedging instruments may destabilize markets when traders are heterogeneous and adapt their behavior according to experience based reinforcement learning. We investigate three different economic settings, a simple mean-variance asset pricing model, a general equilibrium two-period overlapping generations model with heterogeneous expectations and a noisy rational expectations asset pricing model with heterogeneous information signals. In each setting the introduction of additional Arrow securities can destabilize the market, causing a bifurcation of the steady state to multiple steady states, periodic orbits or even chaotic fluctuations

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule

Carzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence-specific alkylating agent. In this phase I study, Carzelesin was given as a 4-weekly 10 min IV infusion to 51 patients with advanced solid tumours. Patients received a median of two courses (range 1–5) at one of nine dose levels: 24, 48, 96, 130, 150, 170, 210, 250 and 300 μg m−2. According to NCI-CTC criteria, non-haematological toxicities (grade 1/2) included fever, nausea and vomiting, mucositis and anorexia, none of which was clearly dose related. The dose-limiting toxicity was haematological and consisted mainly of neutropenia and to a lesser extent thrombocytopenia. From the dose level 150 μg m−2, the haematological toxicity (particularly thrombocytopenia) was delayed in onset, prolonged and cumulative in some patients. In several courses, double WBC nadirs occurred. The maximum tolerated dose for a single course was 300 μg m−2. From the dose level 170 μg m−2, the intended dose intensity could not be delivered to most patients receiving > 2 courses owing to cumulative haematological toxicity. The dose level with the best dose intensity for multiple courses was 150 μg m−2. The pharmacokinetics of Carzelesin and its metabolites (U-76,073; U-76,074) have been established in 31 patients during the first course of treatment using a HPLC method. Carzelesin exhibited linear pharmacokinetics. The concentration of U-76,074 (active metabolite) extended above the lower limit of quantitation (1 ng ml−1) for short periods of time and only at the higher dose levels. There was no relationship between neutropenia and the AUC of the prodrug Carzelesin, but the presence of detectable plasma levels of the active metabolite U-76,074 was usually associated with a substantial decrease in ANC values. © 1999 Cancer Research Campaig

Ground truthing global-scale model estimates of groundwater recharge across Africa

Groundwater is an essential resource for natural and human systems throughout the world and the rates at which aquifers are recharged constrain sustainable levels of consumption. However, recharge estimates from global-scale models regularly disagree with each other and are rarely compared to ground-based estimates. We compare long-term mean annual recharge and recharge ratio (annual recharge/annual precipitation) estimates from eight global models with over 100 ground-based estimates in Africa. We find model estimates of annual recharge and recharge ratio disagree significantly across most of Africa. Furthermore, similarity to ground-based estimates between models also varies considerably and inconsistently throughout the different landscapes of Africa. Models typically showed both positive and negative biases in most landscapes, which made it challenging to pinpoint how recharge prediction by global-scale models can be improved. However, global-scale models which reflected stronger climatic controls on their recharge estimates compared more favourably to ground-based estimates. Given this significant uncertainty in recharge estimates from current global-scale models, we stress that groundwater recharge prediction across Africa, for both research investigations and operational management, should not rely upon estimates from a single model but instead consider the distribution of estimates from different models. Our work will be of particular interest to decision makers and researchers who consider using such recharge outputs to make groundwater governance decisions or investigate groundwater security especially under the potential impact of climate change

No association between islet cell antibodies and coxsackie B, mumps, rubella and cytomegalovirus antibodies in non-diabetic individuals aged 7–19 years

Viral antibodies were tested in a cohort of 44 isletcell antibody-positive individuals age 7–19 years, and 44 of their islet cell antibody-negative age and sex-matched classmates selected from a population study of 4208 pupils who had been screened for islet cell antibodies. Anti-coxsackie B1-5 IgM responses were detected in 14 of 44 (32%) of the islet cell antibody-positive subjects and in 7 of 44 (16%) control subjects. This difference did not reach the level of statistical significance. None of the islet cell antibody-positive subjects had specific IgM antibodies to mumps, rubella, or cytomegalovirus. There was also no increase in the prevalence or the mean titres of anti-mumps-IgG or IgA and anti-cytomegalovirus-IgG in islet cell antibody-positive subjects compared to control subjects. These results do not suggest any association between islet cell antibodies, and possibly insulitis, with recent mumps, rubella or cytomegalo virus infection. Further studies are required to clarify the relationship between islet cell antibodies and coxsackie B virus infections

NMR studies of singlet-ground-state rare-earth ions in high-Tc superconductors

Many of presently known high-Tc superconductors contain rare-earth (RE) ions with an even number of electrons in an unfilled 4f-shell (Pr3+, Tb3+, Ho3+, Tm3+). If the ground state of 4f-electrons is non-degenerate and separated from excited states by high enough energy intervals, one can observe the so-called "enhanced NMR" of RE nuclei at low temperatures. In the present paper some aspects of the enhanced NMR are analyzed in applications to the crystal and electron structure of high-Tc superconductors. © 1992 Springer