Numerical Continuation and Bifurcation Analysis in a Harvested Predator-Prey Model with Time Delay using DDE-Biftool

Time delay has been incorporated in models to reflect certain physical or biological meaning. The theory of delay differential equations (DDEs), which has seen extensive growth in the last seventy years or so, can be used to examine the effects of time delay in the dynamical behavior of systems being considered. Numerical tools to study DDEs have played a significant role not only in illustrating theoretical results but also in discovering interesting dynamics of the model. DDE-Biftool, which is a Matlab package for numerical continuation and numerical bifurcation analysis of DDEs, is one of the most utilized and popular numerical tools for DDEs. In this paper, we present a guide to using the latest version of DDE-Biftool targeted to researchers who are new to the study of time delay systems. A short discussion of an example application, which is a harvested predator-prey model with a single discrete time delay, will be presented first. We then implement this example model in DDE-Biftool, pointing out features where beginners need to be cautious. We end with a comparison of our theoretical and numerical results

Children's International Polyposis (CHIP) study : a randomized, double-blind, placebo-controlled study of celecoxib in children with familial adenomatous polyposis

Objective: To evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyposis in children with familial adenomatous polyposis (FAP). Methods: In this Phase III, double-blind, randomized, placebo-controlled, multicenter trial patients aged 10-17 years with FAP were randomized to celecoxib (16 mg/kg/day) or placebo for up to 5 years. Patients underwent annual assessments, including colonoscopies, to detect the time from randomization to the earliest occurrence of >= 20 polyps (> 2 mm in size) or colorectal malignancy. The study was terminated early due to low rate of observed endpoints combined with a lower than expected enrollment rate. Descriptive results are provided. Results: Of 106 randomized patients, 55 were treated with celecoxib (mean age 12.6 years; 52.7% female) and 51 were given placebo (mean age 12.2 years; 54.9% female). Disease progression (>= 20 polyps, > 2 mm in size) was observed in seven (12.7%) and 13 (25.5%) patients, respectively. The median time to disease progression was 2.1 years in the celecoxib group and 1.1 years for placebo. No patient developed colorectal cancer. The rate of adverse events (AEs) was similar in both groups (75.5% and 72.9%, respectively). Three patients in the celecoxib group (none in the placebo group) experienced serious AEs. Conclusion: In children with FAP, celecoxib was a well-tolerated treatment that was associated with a lower rate of colorectal polyposis and a longer time to disease progression compared with placebo. Due to the low rate of observed endpoints, the long-term impact of these results could not be ascertained

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

Phylogeny of Cyperaceae Based on DNA Sequence Data–a New rbcL Analysis

Since the Monocots II meeting in 1998, significant new data have been published that enhance our systematic knowledge of Cyperaceae. Phylogenetic studies in the family have also progressed steadily. For this study, a parsimony analysis was carried out using all rbcL sequences currently available for Cyperaceae, including data for two new genera. One of the four subfamilies (Caricoideae) and seven of the 14 tribes (Bisboeckelereae, Cariceae, Cryptangieae, Dulichieae, Eleocharideae, Sclerieae, Trilepideae) are monophyletic. Subfamily Mapanioideae and tribe Chrysitricheae are monophyletic if, as the evidence suggests, Hellmuthia is considered a member of Cypereae. Some other features of our analysis include: well-supported Trilepideae and Sclerieae–Bisboeckelereae clades; a possible close relationship between Cryptangieae and Schoeneae; polyphyletic tribes Schoeneae and Scirpeae; the occurrence of Cariceae within the Dulichieae–Scirpeae clade, and a strongly supported clade, representing Cyperus and allied genera in Cypereae, sister to a poorly supported Ficinia–Hellmuthia– Isolepis–Scirpoides clade. Such patterns are consistent with other studies based on DNA sequence data. One outcome may be that only two subfamilies, Mapanioideae and Cyperoideae, are recognized. Much further work is needed, with efforts carefully coordinated among researchers. The work should focus on obtaining morphological and molecular data for all genera in the family

Delay in referral of oropharyngeal squamous cell carcinoma to secondary care correlates with a more advanced stage at presentation, and is associated with poorer survival

Squamous carcinoma of the oropharynx presents with symptoms common to many benign diseases, and this can cause delay in referral to secondary care. We investigate delay in referral, defining this as the time from symptom-onset to date of general practitioners referral letter to secondary care, and the effect of that delay, using a retrospective case notes based study of patients presenting at our institution with oropharyngeal squamous carcinoma between 1995 and 2005. Using correlation analysis and ordinal regression, we examined the relationship between increased referral delay from primary care, clinical stage at presentation, and survival. Increasing time from symptom onset to referral to secondary care was positively correlated with more advanced disease stage at presentation (rs=+0.346, P=0.004). This was confirmed with ordinal regression modelling (delay estimate=0.045, P=0.042). Patients with delay of less than 6 weeks had significantly improved survival compared to those with a delay of greater than 6 weeks (P=0.032). For every 1 week of delay in referral, we estimate that the stage of presentation will progress by 0.045 of ‘a stage'

Continuation for thin film hydrodynamics and related scalar problems

This chapter illustrates how to apply continuation techniques in the analysis of a particular class of nonlinear kinetic equations that describe the time evolution through transport equations for a single scalar field like a densities or interface profiles of various types. We first systematically introduce these equations as gradient dynamics combining mass-conserving and nonmass-conserving fluxes followed by a discussion of nonvariational amendmends and a brief introduction to their analysis by numerical continuation. The approach is first applied to a number of common examples of variational equations, namely, Allen-Cahn- and Cahn-Hilliard-type equations including certain thin-film equations for partially wetting liquids on homogeneous and heterogeneous substrates as well as Swift-Hohenberg and Phase-Field-Crystal equations. Second we consider nonvariational examples as the Kuramoto-Sivashinsky equation, convective Allen-Cahn and Cahn-Hilliard equations and thin-film equations describing stationary sliding drops and a transversal front instability in a dip-coating. Through the different examples we illustrate how to employ the numerical tools provided by the packages auto07p and pde2path to determine steady, stationary and time-periodic solutions in one and two dimensions and the resulting bifurcation diagrams. The incorporation of boundary conditions and integral side conditions is also discussed as well as problem-specific implementation issues

Linking EORTC QLQ-C-30 and PedsQL/PEDQOL physical functioning scores in patients with osteosarcoma

PURPOSE: The available questionnaires for quality-of-life (QoL) assessments are age-group specific, limiting comparability and impeding longitudinal analyses. The comparability of measurements, however, is a necessary condition for gaining scientific evidence. To overcome this problem, we assessed the viability of harmonising data from paediatric and adult patient-reported outcome (PRO) measures. METHOD: To this end, we linked physical functioning scores from the Paediatric Quality of Life Inventory (PedsQL) and the Paediatric Quality of Life Questionnaire (PEDQOL) to the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) for adults. Samples from the EURAMOS-1 QoL sub-study of 75 (PedsQL) and 112 (PEDQOL) adolescent osteosarcoma patients were concurrently administered both paediatric and adult questionnaires on 98 (PedsQL) and 156 (PEDQOL) occasions. We identified corresponding scores using the single-group equipercentile linking method. RESULTS: Linked physical functioning scores showed sufficient concordance to the EORTC QLQ-C30: Lin's ρ = 0.74 (PedsQL) and Lin's ρ = 0.64 (PEDQOL). CONCLUSION: Score linking provides clinicians and researchers with a common metric for assessing QoL with PRO measures across the entire lifespan of patients

Stargardt disease:monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry

PURPOSE: To assess the incidence of Stargardt disease (STGD1) and to evaluate demographics of incident cases. METHODS: For this retrospective cohort study, demographic, clinical and genetic data of patients with a clinical diagnosis of STGD1 were registered between September 2010 and January 2020 in a nationwide disease registry. Annual incidence (2014-2018) and point prevalence (2018) were assessed on the basis of this registry. RESULTS: A total of 800 patients were registered, 56% were female and 83% were of European ancestry. The incidence was 1.67-1.95:1,000,000 per year and the point prevalence in 2018 was approximately 1:22,000-1:19,000 (with and without 10% of potentially unregistered cases). Age at onset was associated with sex (p = 0.027, Fisher's exact); 1.9x more women than men were observed (140 versus 74) amongst patients with an age at onset between 10 and 19 years, while the sex ratio in other age-at-onset categories approximated one. Late-onset STGD1 (≥45 years) constituted 33% of the diagnoses in 2014-2018 compared to 19% in 2004-2008. Diagnostic delay (≥2 years between the first documentation of macular abnormalities and diagnosis) was associated with older age of onset (p = 0.001, Mann-Whitney). Misdiagnosis for age-related macular degeneration (22%) and incidental STGD1 findings (14%) was common in patients with late-onset STGD1. CONCLUSION: The observed prevalence of STGD1 in real-world data was lower than expected on the basis of population ABCA4 allele frequencies. Late-onset STGD1 was more frequently diagnosed in recent years, likely due to higher awareness of its phenotype. In this pretherapeutic era, mis- and underdiagnosis of especially late-onset STGD1 and the role of sex in STGD1 should receive special attention