Disease-induced chaos, coexistence, oscillations, and invasion failure in a competition-model with strong Allee effect.

Biological invasions have impacts on diverse social, ecological, and economic issues. Among others, invasion success can be determined by epidemiological aspects, intraspecific dynamics as, e.g., Allee effects, and interspecific interactions as, e.g., competition. In this study, a process-based model describing competitive eco-epidemiological dynamics of two species, which are both subject to an Allee effect, is developed. Only one of the species can be infected by an infectious disease which is transmitted both, horizontally and vertically. The local dynamics of the disease-free competition model, the competition-free SI-model, and the full eco-epidemiological model are considered. In particular, it is shown that an outbreak of a disease is more likely in the absence of a competitor. Thus, competition and species richness can increase disease resistance of particular species in a community. The complete partial differential equation model is investigated both, analytically and numerically in order to determine possible impacts of the disease on the invasion dynamics. It is shown that in case of strong competition, invasion fronts are always slowed down or even reversed due to the infection for parameter regimes in which the invader is the stronger competitor in the absence of the disease while in case of weak competitive pressure, the dynamics are more complex. Besides slowing down of the invasion front, disease-induced chaos, coexistence (i.e., coexistence in a regime in which coexistence without disease would not be possible), and oscillations can occur. Furthermore, spatial spread can temporarily prevent an infected population from going extinct with potentially detrimental impacts for the resident. This happens via a (replicating) traveling pulse which pushes the competitor out of the domain. The results are discussed in order to enhance the understanding of mechanisms underlying biological invasions and to develop better management strategies for biological invasions as, e.g., selective infections.

Wave pinning in competition-diffusion models in variable environments.

Numerical results on conditions for the emergence of propagation failure of diffusive fronts in two-species competition models for populations with either logistic growth or strong Allee effect are presented. Particularly, the stability against environmental perturbations is investigated. Two different density dependencies of the noise intensities are considered. They mimic a differential functional response of the competitors to the variable environment. Assuming classical linearly density-dependent noise intensities, stochastic wave pinning can occur. This is an ecologically important finding regarding biological invasion as it means that the invasion speed can be reduced by environmental perturbations even yielding a reversal of the invasion wave. However, this depends on the form of the functional per-capita noise response.

[Invasion of an intermediate predator: the dynamics of fish populations in the mathematical model of a trophic chain (as applied to the Syamozero lake)].

We present a mathematical model of the dynamics of a spatially heterogeneous predator-prey population system. A prototype of the model system is the Syamozero lake fish community. We study the impact of the invader, an intermediate predator, on the dynamics of the fish community. We show that the invasion can lead to the appearance of chaotic oscillations in the population density. We show also that different dynamical regimes resulting from the invasion, i.e., stationary, non-chaotic oscillatory and chaotic ones, can coexist. The "choice" of a specific regime therewith depends on the initial invader density. Our analysis of solutions of the mathematical models shows that the successful invasion of the alien species takes place solely in the absence of the competition between the invaders and the native species.

[Evolution of rotifer population dynamics in a heterogeneous habitat: mathematical modeling].

We present the results of mathematical modeling of a rotifer species inhabiting two coupled habitats with different environmental conditions. We use the modified Consensus model and show that the exchange between the habitats can lead to chaotization of originally regular plankton dynamics and synchronization of plankton biomass oscillations. As a result, the invasion of a chaotic regime takes place.

Analysis of the therapeutic efficacy of different doses of budesonide in patients with active Crohn's ileocolitis depending on disease activity and localization.

BACKGROUND AND AIMS: The nonsystemic steroid budesonide has been used to treat active ileocecal and ileocolonic Crohn's disease (CD). This study investigated the optimal budesonide dose using a pH-dependent release formulation. The goal of treatment was the remission of CD (CDAI <150) within 6 weeks of treatment. PATIENTS AND METHODS: The study was of randomized, double-blind, dose-finding design. Patients with active CD ileocolitis without steroid pretreatment were treated with 3x2 mg ( n=39), 3x3 mg ( n=33), or 3x6 mg ( n=32) oral pH-modified released budesonide daily. RESULTS: The remission rates after 6 weeks were 36% with 3x2 mg, 55% with 3x3 mg, and 66% with 3x6 mg. Significantly more patients were in remission while treated with 3x6 mg than with 3x2 mg budesonide/day. Subgroup analyses revealed that patients with high disease activity (CDAI >/= 300) or ileocolonic disease with disease manifestation distal to the transverse colon responded better to the highest budesonide dose. CONCLUSION: Oral pH-modified released budesonide shows a dose-dependent effectiveness in patients with active ileocolonic CD. In the majority of patients 9 mg budesonide per day is sufficient. However, in patients with highly active disease or ileal disease with distal colonic manifestation higher doses of budesonide could increase the therapeutic response

[Effect of the rate of phytoplankton growth on the spaced-time dynamics of plankton communities in an homogeneous environment]. / Vliianie skorosti rosta fitoplanktona na prostranstvenno-vremennuiu dinamiku planktonnykh soobshchestv v neodnorodnoi srede obitaniia.

We use a conceptual mathematical reaction-diffusion model to investigate the mechanisms of spatial structure formation and complex temporal dynamics of plankton in a heterogeneous environment. We take into account basic trophic interactions, namely, "prey-predator" interactions between phytoplankton, zooplankton, and fish in upper layers of natural waters. We consider plankton as a passive contaminant in turbulent waters. We show that plankton structure formation can result from the difference in phytoplankton growth rate in neighboring habitats. Phytoplankton and zooplankton biomass is shown to undergo both regular and chaotic oscillations. The fish predation rate substantially affects the spatial and temporal dynamics of plankton in a heterogeneous environment.

[Interdependence of plankton spatial distribution and plancton biomass temporal oscillations: mathematical simulation]. / Vzaimozavisimost' raspredeleniia planktona v prostranstve i izmenenii biomassy planktona vo vremeni: matematicheskoe modelirovanie.

The dynamics of aquatic biological communities in a patchy environment is of great interest in respect to interrelations between phenomena at various spatial and time scales. To study the complex plankton dynamics in relation to variations of such a biologically essential parameter as the fish predation rate, we use a simple reaction-diffusion model of trophic interactions between phytoplankton, zooplankton, and fish. We suggest that plankton is distributed between two habitats one of which is fish-free due to hydrological inhomogeneity, while the other is fish-populated. We show that temporal variations in the fish predation rate do not violate the strong correspondence between the character of spatial distribution of plankton and changes of plankton biomass in time: regular temporal oscillations of plankton biomass correspond to large-scale plankton patches, while chaotic oscillations correspond to small-scale plankton patterns. As in the case of the constant fish predation rate, the chaotic plankton dynamics is characterized by coexistence of the chaotic attractor and limit cycle.

Fat composition may be a clue to explain the primary therapeutic effect of enteral nutrition in Crohn's disease: results of a double blind randomised multicentre European trial.

BACKGROUND: Dietary fat has been suggested to determine the therapeutic effect of enteral diets in Crohn's disease. AIM: To assess the efficacy of two whole protein based diets with different fat compositions (n6 polyunsaturated fatty acids v monounsaturated fatty acids) in inducing clinical remission in active Crohn's disease compared with steroids. METHODS: Sixty two patients with active Crohn's disease were randomised to receive, for not more than 4 weeks: (a) a polymeric enteral diet containing 35 g of lipids per 1000 kcal, high in oleate (79%) and low in linoleate (6.5%) (PEN1), (b) an identical enteral diet except for the type of fat which was high in linoleate (45%) and low in oleate (28%) (PEN2), or (c) oral prednisone (1 mg/kg/day). Diets were double blindly administered. The steroid group received a conventional ward diet. Treatment failure was considered when remission was not achieved at week 4. Clinical activity and biological and nutritional parameters were monitored. Independent predictors of remission were identified by stepwise logistic regression analysis. RESULTS: Overall remission rates (by intention to treat) were 20% (4/20) for PEN1, 52% (12/23) for PEN2, and 79% (15/19) for steroids (overall p=0.001; p<0.0005 steroids v PEN1, and p=0.056 PEN2 v PEN1). After excluding those patients who were non-compliant during the first week (per protocol analysis), remission rates were 27%, 63%, and 79%, respectively (p=0.008, steroids and PEN2 v PEN1). After adjusting for confounding variables, PEN1 remained significantly associated with a poor response. CONCLUSION: The type of dietary fat may be of importance for the primary therapeutic effect of enteral nutrition in active Crohn's disease.

A new mesalazine foam enema (Claversal Foam) compared with a standard liquid enema in patients with active distal ulcerative colitis.

BACKGROUND: Rectally administered mesalazine (5-aminosalicylic acid) is a recognized therapy for distal ulcerative colitis. It is frequently applied as a liquid enema. However, there are reasons (acceptability to the patient, more uniform topical dispersion and effective adhesion) to prefer a foam-based enema. AIM: This study compared a foam enema (2 g mesalazine per day, Claversal Foam) with a standard liquid enema (4 g mesalazine per day, Salofalk enema). METHODS: Patients with active distal ulcerative colitis, diagnosed according to standardized criteria, were treated for 4 weeks. The primary goal was clinical remission; endoscopic remission, histological changes, global assessment and standard safety measures were also analysed. A major subset of the patients also provided quality-of-life data. RESULTS: Both foam and liquid enema gave good rates of clinical and endoscopic remission. The foam enema was shown to be as efficacious as the reference, even though the daily dose in the foam treatment contained only half as much active drug as in the reference treatment. Minor regional differences in efficacy were seen. The tolerabilities of the two formulations were comparable. CONCLUSIONS: The foam enema offers a safe, efficacious and acceptable treatment for distal ulcerative colitis.

Low ileal interleukin 10 concentrations are predictive of endoscopic recurrence in patients with Crohn's disease.

BACKGROUND: Endoscopic recurrence after surgery in Crohn's disease is frequent and unpredictable. Abnormal intestinal production of pro- (interleukin (IL)-1 beta, tumour necrosis factor alpha (TNF-alpha)) and anti- (IL-10) inflammatory cytokines has been associated with severe outcome in experimental models of colitis. PATIENTS AND METHODS: We evaluated if ileal TNF-alpha, IL-1 beta, or IL-10 mRNA levels measured at the time of surgery predict endoscopic recurrence, and if ileal IL-10 levels are associated with particular IL-10 promoter alleles. Ileal biopsies were obtained peroperatively from the healthy neoileum of patients undergoing a right ileocolectomy for Crohn's disease. Mucosal TNF-alpha, IL-1 beta, and IL-10 mRNA levels were quantified by competitive polymerase chain reaction. A cut off value was determined using a receiver operating curve. IL-10.G promoter haplotypes were analysed using a polymorphic dinucleotide repeat in the IL-10 promoter region. RESULTS: Three months after surgery, 53% of patients had endoscopic recurrence while 47% remained free of disease. The risk of endoscopic recurrence correlated with ileal IL-10 mRNA concentrations (r(2)=0.81). Endoscopic recurrence occurred more frequently in patients classified as low IL-10 producers than in those that were high producers (80% v 40%) (p=0.02). Patients with at least one of the two alleles G7-8 or G10-13 produced, respectively, higher (p=0.006) and lower (p=0.029) ileal IL-10 mRNA. The distribution of IL-10.G microsatellite genotypes was similar in patients with or without endoscopic recurrence. CONCLUSION: Low ileal IL-10 mRNA concentration is a good marker of endoscopic recurrence in Crohn's disease but the distribution of IL-10.G haplotypes cannot predict the postoperative evolution of the disease.

Patchy environment as a factor of complex plankton dynamics.

We study the role of the diffusive interaction in plankton dynamics in a patchy environment. We use a minimal reaction-diffusion model of the nutrient-plankton-fish food chain to simulate the diffusive interaction between fish-populated and fish-free habitats. We show that such interaction can give rise to spatiotemporal plankton patterns. The plankton dynamics depend on the fish predation rate and can exhibit both regular and chaotic behavior. We show that limit cycle and chaotic attractor coexist in the system. The entire basin of attraction of the limit cycles is found to be riddled with "holes" leading to the competitive chaotic attractors. The chaotic dynamics is typical of a wide range of the fish predation rates.

Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease.

BACKGROUND AND AIMS: New lesions of Crohn's disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn's disease. We also assessed the effect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery. METHODS: Patients with Crohn's disease who underwent curative ileal or ileocolonic resection and primary anastomosis were randomised within two weeks after surgery to receive subcutaneous Tenovil 4 microg/kg once daily (QD) (n=22) or 8 microg/kg twice weekly (TIW) (n=21), or placebo (QD or TIW) (n=22). An ileocolonoscopy was performed after 12 weeks of treatment. RESULTS: Compliance was excellent. The most frequently observed adverse events were mild and moderate in severity and equally distributed across treatment groups. Thirty seven patients in the pooled Tenovil group and 21 patients in the pooled placebo group were evaluable by endoscopy. At 12 weeks, 11 of 21 patients (52%) in the placebo group had recurrent lesions compared with 17 of 37 patients (46%) in the Tenovil group (ns). The incidence of severe endoscopic recurrence was similar in both groups (9%). CONCLUSION: Tenovil treatment for 12 consecutive weeks in patients with Crohn's disease after intestinal resection was safe and well tolerated. No evidence of prevention of endoscopic recurrence of Crohn's disease by Tenovil was observed.

Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease.

BACKGROUND & AIMS: ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD). METHODS: A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI <150) at week 14. RESULTS: Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose <10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups. CONCLUSIONS: The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.

Wave of chaos: new mechanism of pattern formation in spatio-temporal population dynamics.

The dynamics of a simple prey-predator system is described by a system of two reaction- diffusion equations with biologically reasonable non-linearities (logistic growth of the prey, Holling type II functional response of the predator). We show that, when the local kinetics of the system is oscillatory, for a wide class of initial conditions the evolution of the system leads to the formation of a non-stationary irregular pattern corresponding to spatio-temporal chaos. The chaotic pattern first appears inside a sub-domain of the system. This sub-domain then steadily grows with time and, finally, the chaotic pattern invades the whole space, displacing the regular pattern.

Biological factors underlying regularity and chaos in aquatic ecosystems: simple models of complex dynamics.

This work is focused on the processes underlying the dynamics of spatially inhomogeneous plankton communities. We demonstrate that reaction-diffusion mathematical models are an appropriate tool for searching and understanding basic mechanisms of complex spatio-temporal plankton dynamics and fractal properties ofplanktivorous fish school walks

Chaos and regular dynamics in model multi-habitat plankton-fish communities.

This work is focused on the role of diffusive interaction between separate habitats in a patchy environment in plankton pattern formation. We demonstrate that conceptual reaction-diffusion mathematical models constitute an appropriate tool for searching and understanding basic mechanisms of plankton pattern formation and complex spatio-temporal plankton dynamics

Switch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease.

BACKGROUND: Steroid dependent patients with Crohn's disease are at high risk of developing glucocorticosteroid induced side effects. AIMS: We evaluated the possibility of switching from systemic steroids to budesonide (Entocort) in prednisolone/prednisone dependent patients with inactive Crohn's disease affecting the ileum and/or ascending colon. PATIENTS: Steroid dependent patients with a Crohn's disease activity index 200 and an increase of 60 points from baseline or withdrawal due to disease deterioration. RESULTS: After one and 13 weeks without prednisolone, relapse rates were 17% and 32%, respectively, in the budesonide group, and 41% and 65% in the placebo group (95% confidence intervals for the difference in percentages -41%, -8% and -51%, -16%; p=0.004 and p<0.001, respectively). The number of glucocorticosteroid side effects was reduced by 50% by switching from prednisolone and was similar in the budesonide and placebo groups. Basal plasma cortisol increased in both groups. CONCLUSIONS: The majority of patients with steroid dependent ileocaecal Crohn's disease may be switched to budesonide controlled ileal release capsules 6 mg without relapse, resulting in a sharp decrease in glucocorticosteroid side effects similar to placebo, and with an increase in plasma cortisol levels.

[The role of carnivorous zooplankton in dynamics of trophic interaction of fish and plankton]. / Rol' plotoiadnogo zooplanktona v dinamike troficheskikh vzaimodeistvii ryby i planktona.

A conceptual (minimal) model of the aquatic community is proposed, which includes phytoplankton, zooplankton, fish and fish larvae. It is shown that carnivorous zooplankton increases the system stability when the fish predation changes. As a result, the system collapse followed by algal bloom becomes less probable.

Motional instabilities in prey-predator systems.

Differential fluxes can destabilize the locally stable stationary density distributions in interaction systems with diffusion, advection, and/or locomotion of chemical or biological species. By this method they can cause the formation of stationary or travelling spatial structures. Different scenarios of this general mechanism of spatio-temporal pattern formation in reaction-diffusion-advection systems will be demonstrated, using a simple two-species predator-prey system as an example model.

Attachment representation and cortisol response to the adult attachment interview in idiopathic spasmodic torticollis.

OBJECTIVE: The study investigates individual differences in the mental representation of attachment and their impact on the cortisol response to psychosocial stress in idiopathic spasmodic torticollis (IST). It was hypothesized (a) that in IST insecure attachment is more prevalent than in a non-clinical control group and (b) that subjects with dismissing attachment respond with higher physiological arousal to a specific stimulus activating the attachment behavioural system than subjects with secure attachment. METHOD: 20 patients with IST and 20 healthy controls matched for age and sex underwent the Adult Attachment Interview, an hour-long, semiclinical interview on attachment experiences. During the interview salivary cortisol levels were monitored. The subjects' mental state with regard to attachment was classified using the attachment Q-sort method. Anxiety and depression were measured as potential covariates of the adrenocortical stress response. RESULTS: Compared to the non-clinical group, dismissing attachment was strongly overrepresented in IST. In IST, but not in the healthy control group, dismissing attachment correlated with an elevated cortisol response to the interview. CONCLUSION: In clinical, but not in non-clinical samples dismissing attachment may be associated with increased vulnerability to psychosocial stress. The factors contributing to this interaction are not yet fully elucidated.