Critical delay for overshooting in planned arm movements with delayed feedback

The Vector Integration To Endpoint (VITE) circuit describes a real time neural network model which simulates behavioral and neurobiological properties of planned arm movements by the interaction of two populations of neurons. This model is generalized to include delay between the interacting populations, which is found to have a detrimental effect on movement accuracy. Conditions are given on the model parameters for accurate movement and target overshoot, where we show that there exists a non-zero critical value of the delay which the circuit can support while maintaining accurate movement. This critical delay depends on the movement speed, and becomes arbitrarily large for sufficiently slow movement. Thus neurobiological or artificial systems modelled by the VITE sensory-motor loop can tolerate an arbitrarily large delay if the movement speed is sufficiently slow.Acknowledgement This project was partially supported by Mathematics for Information Technology and Complex Systems, by the Canada Research Chairs program, and by the Natural Science and Engineering Research Council of Canada.     

Relations between delay discounting and low to moderate gambling, cannabis, and alcohol problems among university students

Research has generally demonstrated that the discounting of delayed rewards is associated with severity of addictive behaviour. Less clear, however, is the relative strength of the relation for specific addictive behaviours. University students (N = 218) completed a computerized delay discounting task for hypothetical monetary rewards, and gambling, cannabis, and alcohol problem severity was assessed. A multiple regression analysis revealed that while the overall model was significant, only gambling problem severity accounted for delay discounting scores above and beyond cannabis and alcohol problem severity. The results support the hypothesis that delay discounting of hypothetical monetary rewards is more associated with gambling than other addictive behaviour problems, including substance use problems.     

Impacts of Incubation Delay on the Dynamics of an Eco-Epidemiological System—A Theoretical Study

Parasite and predator play significant role in trophic interaction, productivity and stability of an ecosystem. In this paper, we have studied a host-parasite-predator interaction that incorporates incubation delay. How the qualitative and quantitative behaviors of the system alter with the incubation delay have been discussed both from mathematical and biological point of views. It is observed that for a lower infection rate, the system is stable for all delays; but for a higher infection rate, there exists a threshold value of the delay above which the system is unstable and below which the system is stable leading to the persistence of all the species. Also, the instability arising from the incubation delay may be controlled if somehow the growth rate of predator population is increased. Numerical studies have also been performed to illustrate different analytical findings. Research is supported by UGC, India; F No. 32-173/2006(SR).     

An epidemiological model with a delay and a nonlinear incidence rate

An epidemiological model with both a time delay in the removed class and a nonlinear incidence rate is analysed to determine the equilibria and their stability. This model is for diseases where individuals are first susceptible, then infected, then removed with temporary immunity and then susceptible again when they lose their immunity. There are multiple equilibria for some parameter values, and, for certain of these, periodic solutions arise by Hopf bifurcation from the large nontrivial equilibrium state.Research supported in parts by Centers for Disease Control Contract 200-87-0515Research supported in part by NSERC A-8965     

Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder

BackgroundBipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare.MethodRetrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay).ResultsThe median diagnostic delay was 62 days (interquartile range: 17–243) and median treatment delay was 31 days (4–122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18–3.06) and treatment delay (4.40, 3.63–5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33–0.41) and substance misuse disorders (0.44, 0.31–0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.ConclusionsSome individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment sooner in order to facilitate improved clinical outcomes, such as developing specialist early intervention services to identify and treat people with bipolar disorder.     

Suppression of pacemaker activity by rapid repetitive phase delay

Spontaneous activity of pacemaker cells or structures may be suppressed by rapid repetitive stimulation. Conditions are that the oscillator's phase reset curve, characterizing the phase resetting effect of single stimuli, has a phase delay part and that the interval between the stimuli falls within a range of values, determined by the form oo the phase reset curve. Under these conditions, which appeared the same as those for stable underdrive pacing, the pacemaker becomes stably entrained to the stimuli without firing, i.e. it is kept within a certian part of its limit cycle because the pulses repeatedly delay the next coming action potential. This rapid stimulation suppression of pacemaker activity is demonstrated experimentally on a simple electronic pacemaker cell model for two types of phase reset curves, a biphasic one for depolarizing and a monophasic one for hyperpolarizing pulses. Computer simulations of coupled pacemaker cells, interacting by phase reset curves, illustrate how this type of pacemaker suppression may protect a population of pacemaker cells like the sinus node in the heart against arrhythmias.Supported by the Netherlands Foundation for Medical Research FUNGOSupported by the Netherlands Organization for the Advancement of Pure Research ZWO     

Decompression of the common peroneal nerve: experience with 20 consecutive cases

A retrospective review of 20 patients with common peroneal nerve palsy treated with decompression between 1986 and 1997 was undertaken. Subjects were evaluated preoperatively and postoperatively by electromyography, nerve conduction, and clinical measures. The mean interval between the onset of symptoms to surgery (operative delay) was 15.9 months. The mean postoperative follow-up was 32.2 months with a minimum follow-up of 1 year. Decompression was performed at the level of the fibular neck and slightly distally at the tendinous origin of the peroneus longus using a standard approach to release tight fascial structures or scar tissue. External neurolysis was performed using the operating microscope in two cases for which scarring of the nerve was identified intraoperatively. Postoperatively, 19 of 20 patients showed improvement in ankle dorsiflexion as assessed by the Medical Research Council scale. Electromyographic examination was useful in the preoperative evaluation and selection of patients for decompression surgery. In conclusion, decompression even after a 1-year delay may offer benefit and suggest early intervention in patients with a severe lesion.     

Discounting of delayed hypothetical money and food: effects of amount

Delay discounting research determines how the value of an outcome is affected by delay to its receipt. Research so far shows that consumable outcomes are discounted more steeply by delay than money. Prior studies, however, have used large amounts of the outcomes (e.g. 100 dollars worth) that would not typically be consumed in one bout, unlike the corresponding amount of money (e.g. 100 dollars ). This experiment examined whether small amounts of food would be discounted more steeply than money, as occurs with larger amounts. One hundred and two adults indicated their preferences in a series of choices for two hypothetical outcome types: immediate versus delayed food and immediate versus delayed money. Participants made choices involving either relatively small maximum amounts of food (10 dollars worth) and money (10 dollars) or for relatively large maximum amounts of food (100 dollars worth) and money (100 dollars ). In the within-subject comparisons, food was discounted more steeply by delay than money for both groups. In the between-subject comparisons, different amounts of the commodities were affected similarly by delay. Overall, these results suggest that steeper discounting of consumable outcomes than money is a fairly robust phenomenon, occurring with relatively small amounts of outcomes as well as with larger amounts.     

An SIS epidemic model with variable population size and a delay

The SIS epidemiological model has births, natural deaths, disease-related deaths and a delay corresponding to the infectious period. The thresholds for persistence, equilibria and stability are determined. The persistence of the disease combined with the disease-related deaths can cause the population size to decrease to zero, to remain finite, or to grow exponentially with a smaller growth rate constant. For some parameter values, the endemic infective-fraction equilibrium is asymptotically stable, but for other parameter values, it is unstable and a surrounding periodic solution appears by Hopf bifurcation.Research Supported in part by NSERC grant A-8965 and the University of Victoria Committee on Faculty Research & Travel     

Some epidemiological models with nonlinear incidence

Epidemiological models with nonlinear incidence rates can have very different dynamic behaviors than those with the usual bilinear incidence rate. The first model considered here includes vital dynamics and a disease process where susceptibles become exposed, then infectious, then removed with temporary immunity and then susceptible again. When the equilibria and stability are investigated, it is found that multiple equilibria exist for some parameter values and periodic solutions can arise by Hopf bifurcation from the larger endemic equilibrium. Many results analogous to those in the first model are obtained for the second model which has a delay in the removed class but no exposed class.Research supported in part by Centers for Disease Control Contract 200-87-0515. Support services provided at University House Research Center at the University of IowaResearch supported in part by NSERC A-8965 and the University of Victoria President's Committee on Faculty Research and Travel     

Pathological gambling severity is associated with impulsivity in a delay discounting procedure

Research and clinical expertise indicates that impulsivity is an underlying feature of pathological gambling. This study examined the extent to which impulsive behavior, defined by the rate of discounting delayed monetary rewards, varies with pathological gambling severity, assessed by the South Oaks Gambling Screen (SOGS). Sixty-two pathological gamblers completed a delay discounting task, the SOGS, the Eysenck impulsivity scale, the Addiction Severity Index (ASI), and questions about gambling and substance use at intake to outpatient treatment for pathological gambling. In the delay discounting task, participants chose between a large delayed reward (US $1000) and smaller more immediate rewards (US $1-$999) across a range of delays (6h to 25 years). The rate at which the delayed reward was discounted (k value) was derived for each participant and linear regression was used to identify the variables that predicted k values. Age, gender, years of education, substance abuse treatment history, and cigarette smoking history failed to significantly predict k values. Scores on the Eysenck impulsivity scale and the SOGS both accounted for a significant proportion of the variance in k values. The predictive value of the SOGS was 1.4 times that of the Eysenck scale. These results indicate that of the measures tested, gambling severity was the best single predictor of impulsive behavior in a delay discounting task in this sample of pathological gamblers.     

Global asymptotic stability of a periodic solution to an epidemic model

In this paper a periodic delay differential equation with spatial spread is investigated. This equation can be used to model the growth of malaria which is transmitted by a mosquito. Using monotone techniques, it is shown that the following bifurcation holds: either the disease dies out or the density of infectious people tends to a spatially homogeneous, time periodic and positive solution.Research partially supported by NSF Grant MCS 810-4837     

Radioautographic,ultrastructural and biochemical studies on the effect of fluorouracil on the RNA synthesis in the liver of rats

Summary The effects of fluorouracil and uracil on the ultrastructure and RNA synthesis in the liver of rats have been studied. High doses of uracil, contrary to fluorouracil, had no effects on nucleolar ultrastructure. Fluorouracil, even in low doses, depressed the RNA synthesis as studied after cytidine-³H administration. In the radioautographs the depression was especially seen to affect the cytoplasmic labelling. The biochemical analysis showed signs of a depression of ribosomal RNA synthesis and a block or delay in the maturation of ribosomal RNA. Repeated, high doses of uracil also depressed the RNA synthesis but there did not seem to be any delay in the maturation of ribosomal RNA. The results suggest that fluorouracil may affect the RNA metabolism in the nucleoli.The investigation was supported by grants from the Swedish Medical Research Council (Project K 67–12 X-623-03), the Swedish Cancer Society (Project 67:31) and the Medical Faculty of Uppsala.     

The transfer function of a photoreceptor organ

summary The dynamic response of a simple ganglionic photoreceptor has been studied. It exemplifies the general processes of sensory reception and transmission of sensory information in the form of trains of nerve impulses. The experimental basis of the defining linear transfer function is presented. This transfer function is composed of a second order lag and a transport delay. The ventral nerve cord conduction time does not contribute to the transport delay. Nonlinear discrepancies from the linear model are evaluated and discussed.This research is supported in part by the Air Force (AF-33(616)-7282); the Office of Naval Research [Nonr-609(39)]: the Army Chemical Corp. (Da-18-108-405-Cml-942); and the U.S. Public Health Service (B-3055, B-3090).     

Pituitary stalk interruption syndrome: diagnostic delay and sensitivity of the auxological criteria of the growth hormone research society

Objectives

To study the diagnostic delay for pituitary stalk interruption syndrome (PSIS) with growth hormone deficiency (GHD) and the sensitivity of the auxological criteria of the Growth Hormone Research Society (GHRS) consensus guidelines.

Methods

A single-center retrospective case-cohort study covering records from January 2000 through December 2007 evaluated the performance of each GHRS auxological criterion for patients with GHD and PSIS. Diagnostic delay was calculated as the difference between the age at which the earliest GHRS criterion could have been observed and the age at diagnosis of PSIS with GHD. A diagnostic delay exceeding one year was defined as late diagnosis.

Results

The study included 21 patients, 16 (76%) of whom had isolated GHD and 5 (24%) multiple pituitary hormone deficiencies. The median age at diagnosis was 3.6 years (interquartile range, IQR, 2.6–5.5). The median diagnostic delay was 2.3 years (range 0–12.6; IQR 1.5–3.6), with late diagnosis for 17 patients (81%). Height more than 1.5 SDS below target height was the most effective criterion: 90% of the patients met the criterion before diagnosis at a median age of 1 year, and it was the first criterion to be fulfilled for 84%.

Conclusion

In our cohort, the delay for diagnosis of PSIS with GHD was long and could have been reduced by using the GHRS criteria, in particular, height more than 1.5 SDS below the target height. The specificity of such a strategy needs to be tested in healthy populations.     

Effects of frequency of the tones on auditory event related potentials in monkeys (Macaca fuscata) under various hypobaric hypoxia conditions of simulated high altitudes

Changes in auditory event related potentials (ERPs) as a function of frequency of tones ranging from 500 Hz to 8,000 Hz were examined under various hypobaric hypoxia conditions of simulated high altitudes up to 6,000 m. A sequence of P₁-N₁-P₂ components, corresponding to those of the human subject, was observed with the monkey's ERPs. These component amplitudes changed as a function of frequency of tone. The relationship revealed an inverted U curve with a maximum amplitude at a tone of 2,000 Hz. The following results under hypoxia were noted: marked reduction of amplitude in ERPs induced by hypoxia linked only to a tone's particular frequency, especially for 2,000 Hz. The delay of latency in the respective components of the ERPs was dependent on the degree of hypoxia. These findings seem to suggest the anatomical bases of the neural generators contributing to each component of the ERPs. This work was supported by the Cooperation Research Program, Primate Research Institute, Kyoto University.     

A mathematical model of cell-to-cell spread of HIV-1 that includes a time delay

 We consider a two-dimensional model of cell-to-cell spread of HIV-1 in tissue cultures, assuming that infection is spread directly from infected cells to healthy cells and neglecting the effects of free virus. The intracellular incubation period is modeled by a gamma distribution and the model is a system of two differential equations with distributed delay, which includes the differential equations model with a discrete delay and the ordinary differential equations model as special cases. We study the stability in all three types of models. It is shown that the ODE model is globally stable while both delay models exhibit Hopf bifurcations by using the (average) delay as a bifurcation parameter. The results indicate that, differing from the cell-to-free virus spread models, the cell-to-cell spread models can produce infective oscillations in typical tissue culture parameter regimes and the latently infected cells are instrumental in sustaining the infection. Our delayed cell-to-cell models may be applicable to study other types of viral infections such as human T-cell leukaemia virus type 1 (HTLV-1). Received: 18 November 2000 / Published online: 28 February 2003 RID="*" ID="*" Research was partially supported by the NSERC and MITACS of Canada and a start-up fund from the College of Arts and Sciences at the University of Miami. On leave from Dalhousie University, Halifax, Nova Scotia, Canada. Current address: Department of Mathematics, Clarke College, Dubuque, Iowa 52001, USA Key words or phrases: HIV-1 – Cell-to-cell spread – Time delay – Stability – Hopf bifurcation – Periodicity     

Two models for a maternal factor in the inheritance of Huntington disease

Huntington disease is a classic example of an autosomal dominant trait. Over the years, however, a number of investigators have reported anomalies regarding the age of onset of the disease that are inconsistent with this paradigm. We propose two models in which a maternal factor--cytoplasmic in one case, autosomal or X-linked in the other--acts to delay onset in a manner consistent with the previously reported anomalies. Relevant data from the Huntington's Disease Research Roster are presented that reinforce and extend the previous observations.     

Optimal filtering of nerve singnals

Recording from multiple electrodes at different sites along a peripheral nerve permits the application of powerful filtering methods to extract the activity of populations of fibres within the nerve which differ in temporal or spectral characteristics. The design of optimal linear filters is initially treated as a general problem in the calculus of variations in which the signals from one population of nerve fibres are extracted so as to minimize those from a second population of nerve fibres or from other sources (noise). A particularly important application arises when the signals at two electrodes are related by weighting functions. In the simplest example the weighting function represents the time delay for nerve impulses to conduct from one electrode to the other, but explicit results are also derivable when there are a range of conduction delays with probabilities distributed according to well-known functions such as the sinc² function.This work was partially supported by the National Research Council of Canada and Medical Research Council of Canada by Grant NRC A-4345 to MNO and Grant MRC MA-3307 to RBS through the University of Alberta     

Modelling Hematopoiesis Mediated by Growth Factors With Applications to Periodic Hematological Diseases

Hematopoiesis is a complex biological process that leads to the production and regulation of blood cells. It is based upon differentiation of stem cells under the action of growth factors. A mathematical approach of this process is proposed to understand some blood diseases characterized by very long period oscillations in circulating blood cells. A system of three differential equations with delay, corresponding to the cell cycle duration, is proposed and analyzed. The existence of a Hopf bifurcation at a positive steady-state is obtained through the study of an exponential polynomial characteristic equation with delay-dependent coefficients. Numerical simulations show that long-period oscillations can be obtained in this model, corresponding to a destabilization of the feedback regulation between blood cells and growth factors, for reasonable cell cycle durations. These oscillations can be related to observations on some periodic hematological diseases (such as chronic myelogenous leukemia, for example). ¹Research was partially supported by the INRIA Futurs, ANUBIS Team. ²Research was partially supported by the NSF and the University of Miami.