Matched Time Intervals Research Articles

Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes

BackgroundPatients with Type 1 diabetes mellitus have been shown to be at a two to ten-fold higher risk of sudden cardiac death (SCD) (Svane et al., Curr Cardiol 2020; 22:112) than the general population, but the underlying mechanism is unclear. Hyperglycaemia is a recognised cause of QTc prolongation; a state patients with type 1 diabetes are more prone to, potentially increasing their risk of ventricular arrhythmia. Understanding the QTc prolongation effect of both hyperglycaemia and the concomitant additive risk of commonly prescribed QTc-prolonging drugs such as Moxifloxacin may help to elucidate the mechanism of sudden cardiac death in this cohort. This single-blinded, placebo-controlled study investigated the extent to which hyperglycaemia prolongs the QTc in controlled conditions, and the potential additive risk of QTc-prolonging medications.Methods21 patients with type 1 diabetes mellitus were enrolled to a placebo-controlled crossover study at a single clinical trials unit. Patients underwent thorough QTc assessment throughout the study. A ‘hyperglycaemic clamp’ of oral and intravenous glucose was administered with a target blood glucose of > 25 mM and maintained for 2 h on day 1 and day 3, alongside placebo on day 1 and moxifloxacin on day 3. Day 2 served as a control day between the two active treatment days.Thorough QTc assessment was conducted at matched time points over 3 days, and regular blood sampling was undertaken at matched time intervals for glucose levels and moxifloxacin exposure.ResultsConcentration-effect modelling showed that acute hyperglycaemia prolonged the QTc interval in female and male volunteers with type 1 diabetes by a peak mean increase of 13 ms at 2 h. Peak mean QTc intervals after the administration of intravenous Moxifloxacin during the hyperglycaemic state were increased by a further 9 ms at 2 h, to 22 ms across the entire study population. Regression analysis suggested this additional increase was additive, not exponential.Hyperglycaemia was associated with a significantly greater mean QTc-prolonging effect in females, but the mean peak increase with the addition of moxifloxacin was the same for males and females. This apparent sex difference was likely due to the exclusive use of basal insulin in the male patients, which provided a low level of exogenous insulin during the study assessments thereby mitigating the effects of hyperglycaemia on QTc. This effect was partially overcome by Moxifloxacin administration, suggesting both hyperglycaemia and moxifloxacin prolong QTc by different mechanisms, based on subinterval analysis.ConclusionsHyperglycaemia was found to be a significant cause of QTc prolongation and the additional effect of a QTc-prolonging positive control (moxifloxacin) was found to be additive. Given the high risk of sudden cardiac death in type 1 diabetes mellitus, extra caution should be exercised when prescribing any medication in this cohort for QTc effects, and further research needs to be undertaken to elucidate the exact mechanism underlying this finding and explore the potential prescribing risk in diabetes.Trial RegistrationNCT number: NCT01984827.Graphical abstract

Optimizing matching time intervals for ride-hailing services using reinforcement learning

Matching trip requests and available drivers efficiently is considered a central operational problem for ride-hailing services. A widely adopted matching strategy is to accumulate a batch of potential passenger-driver matches and solve bipartite matching problems repeatedly. The efficiency of matching can be improved substantially if the matching is delayed by adaptively adjusting the matching time interval. The optimal delayed matching is subject to the trade-off between the delay penalty and the reduced wait cost and is dependent on the system’s supply and demand states. Searching for the optimal delayed matching policy is challenging, as the current policy is compounded with past actions. To this end, we tailor a family of reinforcement learning-based methods to overcome the curse of dimensionality and sparse reward issues. In addition, this work provides a solution to spatial partitioning balance between the state representation error and the optimality gap of asynchronous matching. Lastly, we examine the proposed methods with real-world taxi trajectory data and garner managerial insights into the general delayed matching policies. The focus of this work is single-ride service due to limited access to shared ride data, while the general framework can be extended to the setting with a ride-pooling component.

A General Matching Function for Ride-Sourcing Services

This paper presents a general matching function to delineate the on-demand matching process in ride-sourcing markets under different matching mechanisms with different matching time intervals and matching radius. The matching function characterizes a stationary matching equilibrium for the ride-sourcing market in which passengers can be matched in consecutive batches, and drivers are in either an idle, pick-up, or delivery state. The function well approximates the expected driver idle time and the expected passenger matching time and pick-up time under different supply-demand conditions and platform matching strategies. The general function also unifies several prevailing inductive and deductive matching functions developed in the literature and demonstrates their specific application scope. In particular, when the matching radius is sufficiently small, the function reduces to the Cobb-Douglas-type matching function proposed by Yang and Yang (2011) for street-hailing taxi markets, in which the matching rate depends on the pool size of waiting passengers and idle drivers. Under an instant matching mechanism with a large matching radius, the function reduces to the model of Castillo et al. (Castillo et al. 2017) or a variant of the Cobb-Douglas-type matching function, in which the matching rate depends on the pool size of waiting passengers and drivers in the pick-up phase. In addition, when both the matching time interval and matching radius are relatively large, the function reduces to a variant of the Cobb-Douglas-type matching function.

Optimizing matching time interval and matching radius in on-demand ride-sourcing markets

With the availability of the location information of drivers and passengers, ride-sourcing platforms can now provide increasingly efficient online matching compared with physical searching and meeting performed in the traditional taxi market. The matching time interval (the time interval over which waiting passengers and idle drivers are accumulated and then subjected to peer-to-peer matching) and matching radius (or maximum allowable pick-up distance, within which waiting passengers and idle drivers can be matched or paired) are two key control variables that a platform can employ to optimize system performance in an online matching system. By appropriately extending the matching time interval, the platform can accumulate large numbers of waiting (or unserved) passengers and idle drivers and thus match the two pools with a reduced expected pick-up distance. However, if the matching time interval is excessively long, certain passengers may become impatient and even abandon their requests. Meanwhile, a short matching radius can reduce the expected pick-up distance but may decrease the matching rate as well. Therefore, the matching time interval and matching radius should be optimized to enhance system efficiency in terms of passenger waiting time, vehicle utilization, and matching rate. This study proposes a model that delineates the online matching process in ride-sourcing markets. The model is then used to examine the impact of the matching time interval and matching radius on system performance and to jointly optimize the two variables under different levels of supply and demand. Numerical experiments are conducted to demonstrate how the proposed modeling and optimization approaches can improve the real-time matching of ride-sourcing platforms.

Optimizing Matching Time Interval and Matching Radius In On-Demand Matching of a Ride-Sourcing Market

With the availability of location information on drivers and passengers, ride-sourcing platforms are now able to provide more efficient online matching than the physical searching and meeting in traditional taxi market. The matching time interval (a time interval over which waiting passengers and idle drivers are accumulated and then peer-to-peer matching is executed) and matching radius (or maximum allowable pickup distance, within which matching or pairing between waiting passengers and idle drivers can be done) are two key control variables that the platform can employ to optimize the system performance in an online matching system. By appropriately extending matching time interval, the platform can accumulate more waiting (or unserved) passengers and idle drivers and thus match the two pools with shorter expected pickup distance. However, if the matching time interval is excessively long, some passengers may become impatient, and may even cancel their requests. Meanwhile, a short matching radius can reduce expected pickup distance but may decrease the matching rate as well. Therefore, it is important to optimize the matching time interval and matching radius to enhance system efficiency in terms of passenger waiting time, vehicle utilization and matching rate. This paper proposes a model to delineate the online matching process in a ride-sourcing market. The model is then used to examine the impact of the matching time interval and matching radius on system performance and to jointly optimize the two variables under different levels of supply and demand. Numerical experiments are conducted to demonstrate how the proposed modelling and optimization approaches can improve real-time matching processes of ride-sourcing platforms.

Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Course and Predictors of Arrhythmic Risk

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined. ObjectivesThis study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy. MethodsWe determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry. Predictors of LAE over 5.8 years of follow-up were determined with Cox multivariable analysis. Treatment efficacy was assessed comparing LAE rates during matched time intervals. ResultsA first LAE occurred in 1.5 per 100 person-years between birth and age 20 years, in 4.0 per 100 person-years between ages 21 and 40 years, and in 2.4 per 100 person-years between ages 41 and 60 years. Cumulative probability of a first LAE at follow-up was 14% at 5 years, 23% at 10 years, and 30% at 15 years. Higher risk of LAE was predicted by atrial fibrillation (hazard ratio [HR]: 4.38; p = 0.002), syncope (HR: 3.36; p < 0.001), participation in strenuous exercise after the diagnosis (HR: 2.98; p = 0.028), hemodynamically tolerated sustained monomorphic ventricular tachycardia (HR: 2.19; p = 0.023), and male sex (HR: 2.49; p = 0.012). No difference was observed in the occurrence of LAE before and after treatment with amiodarone, beta-blockers, sotalol, or ablation. A total of 81 patients received an implantable cardioverter-defibrillator, 34 were successfully defibrillated. ConclusionsThe high risk of life-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching its peak between ages 21 and 40 years. Atrial fibrillation, syncope, participation in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ventricular tachycardia, and male sex predicted lethal arrhythmias at follow-up. The lack of efficacy of antiarrhythmic therapy and the life-saving role of the implantable cardioverter-defibrillator highlight the importance of risk stratification for patient management.

Changes in cognitive functions and cerebral grey matter and their associations with inflammatory markers, endocrine markers, and APOE genotypes in testicular cancer patients undergoing treatment.

Evidence suggests that testicular cancer (TC) and its treatment are associated with cognitive impairment. However, the underlying neural substrate and biological mechanisms are poorly understood. This study aimed to investigate changes in cognition and brain grey matter (GM) morphology in TC patients undergoing treatment, and to explore associations with immune markers, endocrine markers, and genotype. Sixty-five patients with stage I-III TC underwent assessment after surgery but prior to further treatment and again 6months after. Twenty-two patients received chemotherapy (+CT), while 43 did not (-CT). Assessments included neuropsychological testing, whole-brain magnetic resonance imaging, and blood samples. Twenty-five healthy controls (HCs) underwent neuropsychological testing with a matching time interval. A regression-based approach was used to determine cognitive changes and longitudinal voxel-based morphometry (VBM) was performed to investigate changes in GM density in the TC groups. Compared with the HCs, both TC groups showed higher rates of cognitive decline (p < 0.05). A trend towards greater decline was observed in + CT (63.6%) compared with -CT patients(39.5%) (p = 0.07). VBM revealed widespread GM reductions in both TC groups, but a group-by-time interaction analysis revealed prefrontal reductions specific to the + CT group (p = 0.02), which were associated with poorer cognitive performance. Poorer cognitive performance was also associated with an increase in tumornecrosis factor alpha in + CTpatients. Furthermore, an interaction effect was found between the APOE ε4 genotype and chemotherapy on cognitive performance with ε4 carriers performing significantly worse. These findings provide novel evidence of changes in cognition and brain morphology in TC patients undergoing treatment.

Input-to-State Stability of Switched Nonlinear Systems With Time Delays Under Asynchronous Switching

This paper is concerned with analyzing input-to-state stability (ISS) for a class of switched nonlinear systems with time delays under asynchronous switching. Due to the existence of switching delay, the switching of the controller does not coincide accurately with the switching of the system.When the subsystem is stabilized with the matched controller, the subsystem is ISS; otherwise, the subsystem may be not ISS. We establish efficient condition, in terms of an upper bound on the switching delay, and in terms of a lower bound on the matched time intervals for the subsystem and the controller, which ensures ISS for the whole switched nonlinear system. Finally, an illustrative example is presented to demonstrate the efficacy of the results.

Detection probability of vocalizing dugongs during playback of conspecific calls

Dugongs (Dugong dugon) were monitored using simultaneous passive acoustic methods and visual observations in Thai waters during January 2008. Chirp and trill calls were detected by a towed stereo hydrophone array system. Two teams of experienced observers conducted standard visual observations on the same boat. Comparisons of detection probabilities of acoustic and visual monitoring between two independent observers were calculated. Acoustic and visual detection probabilities were 15.1% and 15.7%, respectively, employing a 300 s matching time interval. When conspecific chirp calls were broadcast from an underwater speaker deployed on the side of the observation boat, the detection probability of acoustic monitoring rose to 19.2%. The visual detection probability was 12.5%. Vocal hot spots characterized by frequent acoustic detection of calls were suggested by dispersion analysis, while dugongs were visually observed constantly throughout the focal area (p<0.001). Passive acoustic monitoring assisted the survey since detection performance similar to that of experienced visual observers was shown. Playback of conspecific chirps appeared to increase the detection probability, which could be beneficial for future field surveys using passive acoustics in order to ensure the attendance of dugongs in the focal area.

Dupuytren’s Disease: a Predominant Reason for Elective Finger Amputation in Adults

Dupuytren’s disease (DD) can lead to severe disabling finger contractures resistant to surgical treatment. In some cases, finger or ray amputation is considered, due to a severe functional deficit or vascular injury. To evaluate the weight of amputation surgery in DD, a retrospective study was conducted over a 5-year time interval, outlining all indications for elective finger amputation and its prevalence in the total of surgical interventions for DD. The outcome in DD was compared to post-traumatic amputations. Out of 31 elective finger and ray amputations, 12 (39%) were indicated for DD, all in the 4th or 5th ray, of which 92% were in recurrent disease. In the 646 surgical procedures for DD in the matching time interval, we conclude that almost 2% were elective amputations. The outcome of amputation in DD was similar to post-traumatic amputations. Based on these data, we feel that patients should be informed that sometimes, surgical treatment for Dupuytren’s disease can lead to an eventual decision to amputate.

Lower Excess Postexercise Oxygen Consumption and Altered Growth Hormone and Cortisol Responses to Exercise in Obese Men

Obesity is associated with altered patterns of substrate utilization at rest and during exercise. The relationship between obesity and fat oxidation during recovery from exercise was examined. The postexercise shift toward fat oxidation is blunted in the obese state, reflected by higher respiratory exchange ratio (RER), blunted GH, and increased cortisol values compared with lean controls. Each subject completed two 160-min protocols (baseline and exercise). During baseline, subjects rested for 160 min; during exercise, they completed 30 min of cycling at ventilatory threshold, followed by 130 min of rest. This study was performed at the University of Alberta. Healthy untrained (maximal oxygen consumption, <45 ml/kg.min or <3.35 liter/min) lean (<16% body fat; n = 6) and obese (>25% body fat; n = 7) men, aged 30-39 yr, were studied. RER, GH, cortisol, oxygen consumption, heart rate, tympanic temperature, and lactate were obtained during both protocols at matched time intervals and analyzed by repeated measures ANOVA. During baseline, there were no differences detected between lean and obese groups for any of the measured variables. In contrast, during exercise, peak GH levels were blunted (P < 0.05) and cortisol levels were elevated (P < 0.05) in the obese compared with the lean subjects, but RER values were similar in the two groups. The differences in GH and cortisol persisted during the postexercise period accompanied by higher RER values (P < 0.05) and reduced total oxygen consumption (P < 0.05) in the obese group. These findings indicate that exercise-induced fat oxidation is diminished in obese men.

Forcibly driven coherent soft phonons in GeTe with intense THz-rate pump fields

We propose an experimental technique to generate large amplitude coherent phonons with irradiation of THz-rate pump pulses and to study the dynamics of phase transition in GeTe ferroelectrics. When a single pump pulse irradiates the sample at various pump power densities, the frequency of the soft phonon decreases sublinearly and saturates at higher pump powers. By contrast, when the THz-rate pump pulse sequence irradiates the sample at matched time intervals to forcibly drive oscillation, a large redshift of the phonon frequency is observed without any saturation effects. After excitation with a four pump pulse sequence, the coherent soft phonon becomes strongly damped and leads to a near critical damping condition. This condition indicates that the lattice is driven to a precursor state of the phase transition.

Thoracoscopic pleurodesis with minocycline vs talc in the porcine model

Eighteen adult pigs (Sus scrofa) underwent thoracoscopy and were placed into one of three groups: no sclerosant, talc pleurodesis, or minocycline pleurodesis. Animals were then sacrificed at matched time intervals. Gross inspection of the pleural cavity estimated percentage of pleural symphysis (>25% was considered substantial) and allowed assignment of a pleurodesis score based on a scale described by Bresticker. Microscopic examination evaluated degree of fibrosis as mild, moderate, or severe. The talc group had significantly better pleurodesis than the minocycline group as determined by (1) the proportion of animals with substantial surface pleural symphysis (5/6 vs 1/6, p < 0.01), (2) a higher pleurodesis score (3 vs 1.3, p < 0.05), and (3) the proportion of animals with moderate fibrosis (5/6 vs 0/6, p < 0. 01). The authors conclude that instillation of aerosolized talc produces significantly better fibrosis and pleural symphysis than atomized minocycline in this animal model.

A modified selected point matching technique for testing compact heat exchanger surfaces

A transient technique taking care of the longitudinal heat conduction effect is developed in which an experimentally determined T f1 ∗(0 ∗) is used as the inlet fluid temperature condition. It is shown that the longitudinal conduction effect must be included for both N tu ⩾ 3 and λ 1, N tu ⩾ 0.06 and there exists an optimum matching time interval. An empirical formula for correcting the heat conduction effect for N tu ⩽ 20, the optimum matching time interval and an uncertainty analysis are included. The validity of this technique is confirmed by the good agreement between the test data and the theoretically predicated results.

The kinetics of transmitter release at the frog neuromuscular junction.

1. Fluctuations in the latency of focally recorded end-plate currents were analysed to determine the time course of the probabilistic presynaptic process underlying quantal release evoked after single nerve stimuli at the frog neuromuscular junction.2. The early falling phase of the presynaptic probability function can be fitted by a single exponential over two orders of magnitude of quantal release rate. The time constant of the early falling phase is about 0.5 msec at 11 degrees C, and increases with decreasing temperature with a Q(10) of at least 4 over the range 1-12 degrees C.3. After this early exponential fall, quantal release probability returns to control levels with a much slower time course.4. Conditioning nerve stimuli increase the magnitude and slightly prolong the early time course of release evoked by a test stimulus. When facilitation is calculated for matched time intervals following the conditioning and testing stimuli, it is found that the magnitude of the small, late residual tail of release is facilitated by a greater percentage than the magnitude of larger, early portions of release.5. These results are discussed in terms of the hypothesis (Katz & Miledi, 1968) that evoked release and facilitation are mediated by a common presynaptic factor which activates release in a non-linear manner.