Excursion Rate Research Articles

#1755 Cardio-protective effect of soy proteins during long-term consumption of Cynomolgus Monkeys high-saline diet

Abstract Background and Aims High salt intake is accompanied by the development of cardiovascular disorders, not always associated with an increase in blood pressure (BP). Recently, it has been found that the introduction of soy protein into the diet can have some nephroprotective and cardioprotective effects in chronic kidney disease. Considering the cardioprotective effect of soy proteins in chronic kidney disease, the question arose about the possibility of using soy proteins to neutralize the damaging effect of a high-salt diet on the cardiovascular system. This work aims to study the effect of long-term use of a diet high in NaCl and soy protein on myocardial remodeling in monkeys. Method The study was performed on male Macaca fascicularis. The animals were divided into three groups (6 animals each), comparable in weight and age (6-8 years, body weight - 5.15-9.7 kg). The control group received a standard diet (2 g NaCl/kg feed). The second was a high salt diet (8 g NaCl/kg feed), and the third was a high salt diet and SUPRO760 soy protein (200 g/kg feed). Echocardiography (EchoCG), registration of BP and heart rate were performed at baseline, after 4 and 12 months. EchoCG was performed with a sector transducer with a frequency of 3–5 MHz on the Chison SonoTouch 60 ultrasound system (China). EchoCG was performed in B_mode (two-dimensional scanning), M_mode (one-dimensional scanning), as well as in pulse and tissue Doppler modes. Statistical analysis was performed using parametric statistics: mixed ANOVA in comparing data from 3 study groups (with post hoc analysis using Tukey criterion) and single factor variance analysis for related samples in studying the dynamics of one or another index in each group during the 12-month follow-up. Differences were considered significant at p < 0.05. Results In animals of all three groups for 12 months, blood pressure (BPsis-109±10.09, BPdias – 60 ± 7.42 mm Hg) and heart rate (77 ± 12.61 min-1) did not change significantly (p>0. 05). However, in macaques on a high-salt diet, deterioration in left ventricular (LV) systolic and diastolic function was noted by the end of the study. Macaques of this group had a decrease in the LV shortening fraction (27.9±2.69%) and an increase in the thickness of the posterior wall of the LV in systole (0.69±0.039 cm), LV mass (19.60±2.83 g), compared with animals additionally receiving soy proteins (34.9±6.57%; 0.57 0.0559 cm; 14.86±2.94 g, respectively; all p < 0.05). In addition, the monkeys receiving soy isolate did not differ from the control in these parameters. By the time the study was completed, the animals in this group had significantly increased the magnitude of systolic excursion of the mitral annulus plane, and signs of improvement in LV diastolic function appeared in the form of an increase in the maximum rate of excursion of the mitral valve fibrous annulus in early diastole, as well as a decrease in the E/e' ratio. The thickness of the interventricular septum also decreased (0.42±0.04 cm; in the high-salt group - 0.51±0.08 cm), which can be interpreted as a sign of positive myocardial remodeling. Conclusion Thus, high salt intake leads to adverse structural and functional disorders of the heart in cynomolgus monkeys, not associated with an increase in blood pressure. The inclusion of soy isolate in the diet reduces the negative effects of a high-salt diet on the cardiovascular system.

Diagnostics of disturbances in the functional state of the diaphragm in patients with chronic obstructive pulmonary disease after COVID-19

Aim. Assessment of the functional state of the diaphragm in patients with COPD who underwent COVID-19.Materials and methods. The study included 35 patients with COPD complicated by compensated chronic cor pulmonale (CCP): group 1 included 15 patients with COPD who had COVID-19, group 2 included 20 patients with COPD. Patients were examined 3 months after suffering COVID-19. The functional state of the diaphragm was studied using the VIVID S70N ultrasound diagnostic system.Results. The greatest decrease in the diaphragm dome height was detected in the 1st group (p=0.001). The excursion of the diaphragm during quiet breathing was increased in both groups, in the 2nd group the indicator was 11% more than in the 1st group. The diaphragm excursion during forced breathing was reduced in the 1st group (p=0.02). The rate of diaphragm excursion during inhalation and exhalation during quiet and forced breathing in both groups was significantly increased compared to the control group. However, in the 1st group, the rate of diaphragm excursion on expiration was 49% higher. These changes may indicate respiratory muscle fatigue in COPD patients who have had COVID-19. The thickness of the muscular part of the diaphragm during inhalation and exhalation during quiet breathing in both groups compared to the control group was significantly higher. These indicators in both groups did not significantly differ from each other. There was a decrease in the thickening fraction of the muscular part of the diaphragm during calm (p=0.01) and forced breathing (p=0.001) in both groups, which indicates the onset of fatigue of the muscles of the diaphragm in the 2nd group and the initial development of weakness of the diaphragm in the 1st group who had the greatest decrease in this indicator during forced breathing.Conclusion. Ultrasonic diagnostic methods significantly expand the possibilities for assessing the functional state of the diaphragm. Patients with COPD who have undergone COVID-19 are characterized by a significant increase in the thickness of the diaphragm, limitation of its mobility, and a slowdown in the rate of relaxation of the muscular part of the diaphragm.

#3406 CARDIOPROTECTIVE EFFECT OF SOY PROTEIN ON LONG-TERM HIGH-SALT DIET IN CYNOMOLGUS MONKEYS

Abstract Background and Aims A high salt content in the diet is one of the reasons for the increase in blood pressure (BP) and the development of cardiovascular disorders. However, high intake of sodium chloride does not always lead to an increase in blood pressure, but causes endothelial dysfunction and cardiac remodeling. It has been established that the introduction of soy products into the diet can have a nephro- and cardioprotective effect in chronic kidney disease. At the same time, it is not clear whether the damaging effect of a high-salt diet on the cardiovascular system can be offset by other dietary interventions, in particular, soy proteins. In this regard, the aim of the study was to study the effect of long-term use of diets with different content of sodium chloride and soy protein on myocardial remodeling in cynomolgus monkeys. Method A total of 18 cynomolgus male monkeys with age 6–8 years were studied. The animals were divided into three groups (six in each group). The first (control) group received the standard diet. The second group received the diet rich in common salt (8 g of NaCl/kg), and the third, the high salt diet in combination with soy protein SUPRO 760 (200 g/kg; Protеin Tеchnology Intеrnational, USA). Systolic (BP) and diastolic (BPd) blood pressure (BP) in monkeys was recorded by oscillometric method on a veterinary tonometer ML-410 VET (Microlux, Russia) under anesthesia. After registration of blood pressure, an echocardiographic study (EchoCG) was performed with a sector sensor with a frequency of 3-5 MHz on an ultrasound system Chison SonoTouch 60 (China). Echocardiography was performed in B-mode (two-dimensional scanning), M-mode (one-dimensional scanning), as well as in pulsed and tissue Doppler modes. Echocardiography and blood pressure measurements were performed at baseline, after 4 and 12 months of follow-up. Results BP values (group 1 - BPs: 109±10.09, BPd: 60±7.42; group 2 - BPs: 109±25.14, BPd: 57±11.86; group 3 - BPs: 101±8, 59, BPd: 57±6.92 mm Hg, all p>0.05) and heart rate (group 1 - 77±12.61, group 2 - 81±18.07, group 3-80±19.9 beats/min, all p>0.05) in macaques did not undergo significant changes over 12 months of the experiment in any of the groups. In group 1, there were also no significant changes in echocardiographic parameters. Group 2 monkeys showed no early changes in LV shortening fraction (FU) and ejection fraction (EF). However, after 12 months, FU decreased by an average of 26.6%, and EF by 12.8% compared with the indicator for a period of 4 months. In addition, the speed of the transmitral flow in early diastole (E) decreased by 19.1% compared with the baseline. Long-term intake of soy proteins prevented a decrease in LV FU in macaques on a high-salt diet. Its value was 25.1% greater than in group 2. In group 3 monkeys, after 12 months, the magnitude of systolic excursion of the mitral annulus plane and the maximum rate of excursion of the fibrous annulus of the mitral valve in early diastole (e') increased, the thickness of the interventricular septum in diastole decreased, and E/e' ratio. In group 3, the thickness of the posterior wall of the left ventricle decreased in systole (0.57±0.056 mm), the mass of the LV myocardium (14.9±2.94 g/m2), the average diameter of the base of the right ventricle (1.20±0.115 mm) compared with group 2 (0.69±0.040 mm, 19.6±2.83 g/m2, 1.40±0.111 mm, respectively; all p<0.01). Conclusion The obtained results can be considered as confirmation of the hypothesis that high consumption of sodium chloride leads to adverse structural and functional changes in the heart and blood vessels, not associated with an increase in blood pressure. The inclusion of isolated soy proteins in the diet is likely to reduce the effects of this negative impact. The specific mechanisms of this cardioprotective effect remain to be explored. Statistical analysis used One-way analysis of variance for unrelated samples when comparing the data of 3 studied groups and one-way analysis of variance for related samples when studying the dynamics of the indicator in each of the groups during 12 months of observation. Results are presented as mean ± standard deviation (M ± SD). Differences were considered significant at p<0.05.

Improving cycling safety through infrastructure design: A bicycle simulator study

This study investigated the impact of two road treatments on cyclist behaviour using an bicycle simulator. The treatments were sharrows (presence or absence) at a roundabout and widening an on-road bike lane (width 1.2 m or 1.8 m) on a curved mid-block section of the road. Outcomes collected included count (e.g. number of lane excursions) and continuous responses (lane position upon entry into the roundabout, in metres from the curb). A convenience sample of 21 Perth-based participants was recruited between 1 July and 30 September 2021. The results found that the presence of sharrows was not significantly associated with the distance from the left curb when entering a single lane roundabout. However, females rode 0.44 m further from the left curb when entering the roundabout than males, which was significant (95 % CI = 0.02–0.85; p = 0.04). Riders, aged 26–40 years, also rode 0.61 m further from the left curb when entering the roundabout than riders aged 18–25 years, which was also significant (95 % CI = 0.18–1.05; p = 0.01). The rate of bike lane excursions significantly decreased by 68 % for the wide bike lane on the curved mid-block section of the road compared to the standard width bike lane (IRR = 0.32; 95 % CI = 0.11–0.88; p = 0.03). Riders, aged 26–40 years, had a significant increased rate of 8.72 excursions than riders aged 18–25 years (IRR = 8.72; 95 % CI = 3.32–22.89; p < 0.001). This study highlights that increasing the bike lane width on curved sections of mid-block roads may benefit cyclists. However, the value of sharrows in a single lane roundabout is less clear.

The serial changes in myocardial functions after paediatric haematopoietic stem cell transplantation.

The aim of this study is to evaluate the changes in myocardial functions in children who underwent haematopoietic stem cell transplantation along with associated chemotherapy. Additionally, we evaluated the effect of baseline echocardiographic parameters on mortality. We evaluated 39 patients (mean age 7.4 years) who underwent haematopoietic stem cell transplantation owing to non-malignant disease. The control group included 39 healthy children who had normal cardiac findings. The myocardial functions were evaluated in all subjects by conventional echocardiography and tissue Doppler echocardiography before haematopoietic stem cell transplantation and in the 1st, 3rd, 6th, and 12th month after haematopoietic stem cell transplantation. All patients had normal left ventricular ejection fraction before haematopoietic stem cell transplantation, except one case. Before haematopoietic stem cell transplantation, the patient group had significantly greater mean pulmonary artery pressure and lower tricuspid valve annular plane excursion rate. Baseline E' velocities for mitral lateral annuli, septum, and tricuspid lateral annuli were lower in the patient group than the control group. The E' velocities for the left ventricle decreased in the patient group after haematopoietic stem cell transplantation, and then returned to baseline levels at the 6 months. E' and S' velocities for tricuspid lateral annuli also decreased after haematopoietic stem cell transplantation and were still depressed in the first year after haematopoietic stem cell transplantation. Baseline E' velocity for septum was significantly lower in patients who died after haematopoietic stem cell transplantation than patients who survived (p = 0.009). Subclinical impairment in both ventricular functions was observed after haematopoietic stem cell transplantation and the right ventricular functions were affected for longer periods than left ventricle after haematopoietic stem cell transplantation. The myocardial functions should be monitored after the first year of haematopoietic stem cell transplantation.

Glycemic Variability Assessment in Newly Treated Exocrine Pancreatic Insufficiency With Type 1 Diabetes.

Thirty-nine percent of people with type 1 diabetes may have lowered pancreatic elastase levels, correlated with exocrine pancreatic insufficiency (EPI or PEI). EPI is treated with oral supplementation of pancreatic enzymes. Little is known about the glycemic impact of pancreatic enzyme replacement therapy (PERT) in people with diabetes. This article demonstrates a method of assessing glycemic variability (GV), glycemic outcomes, and other changes in an individual with type 1 diabetes using open-source automated insulin delivery (AID). Macronutrient, PERT intake, and EPI-related symptoms were self-tracked; diabetes data were collected automatically via an open-source AID system. Diabetes data were uploaded via Nightscout to Open Humans and downloaded for analysis alongside self-tracked data (food, PERT). Glycemic outcomes, macronutrients, PERT dosing, and a variety of GV metrics following meals were evaluated for one month before and one month after PERT commencement. Breakfast was assessed independently across both time periods. In an n = 1 individual using an open-source AID, time in range was already above goal and improved further after PERT commencement. Glucose rate of change and excursions >180 mg/dL were reduced; mean high blood glucose index was reduced overall and more so specifically at breakfast following PERT commencement. GV can aid in assessing response to new-onset medications, as was demonstrated in this article for n = 1 individual with type 1 diabetes (using an open-source AID) after commencing PERT for newly identified EPI. GV may be useful for evaluating the efficacy of new-onset medications for people with insulin-requiring diabetes.

Evaluating an Automated Temperature-Monitoring System in Medicine and Vaccine Storage Facilities of a Hospital Network

Objective: The aims of this study were to evaluate the effectiveness of a new automated continuous temperature monitoring system in detecting temperature excursions and describe the challenges of implementing such a system. Design: This study is an observational before-and-after audit comparing temperature excursions detected in the three months before and three months after the implementation of the new monitoring system at Eastern Health. Inclusion criteria consisted of all medicine and vaccine storage facilities monitored by the new automated temperature monitoring system. Four sites not connected to the new monitoring system were excluded. Setting: Eastern Health is a large tertiary metropolitan health service in Melbourne, Australia. It operates from 21 locations including seven teaching hospitals, with medicines and vaccines stored in 124 refrigerators, 6 freezers and 101 ambient room temperature storage locations. Main outcome measures: An analysis of post-implementation data identified a potential association between refrigerator brands and temperature excursion rate. Results: There was a large increase in the number of temperature excursions detected post-implementation of the new automated monitoring system. 28746, 24 and 8966 temperature excursions were detected post-implementation compared to 344, 0 and 0 pre-implementation in refrigerators, freezers and ambient locations, respectively. The majority of temperature excursions detected in medicine and vaccine fridges were below +2°C (98.4%). One brand of refrigerators was linked to 27231 (94.7%) excursions (p&lt;0.001). Conclusions: The new temperature monitoring system detects higher number of excursions which provides better visibility of performance, identifies areas of non-compliance, and guides and evaluates solutions. This study recommends that freezers and ambient storage locations are monitored as robustly as refrigerators, temperature monitoring devices are placed in close proximity to pharmaceuticals, and that healthcare organisations avoid purchasing unreliable medicine and vaccine refrigerators. Finally, this study suggests the development of a National Medicine Storage Guideline.

Investigating the Potential Impact of Dosing Tolerance to Facilitate Use of Nplate Self-Administration in Adult Patients with ITP

Background and Objective: Romiplostim, is a TPO agonist approved for the treatment for adult ITP. It follows a weight-based and platelet response-guided dose titration algorithm to maintain patients' platelet counts (PC) between 50 and 200x10 9/L, after which a maintenance dose is administered once weekly to keep platelet counts within the target range. While self-administration of romiplostim maintenance dose has been approved in EU for adult patients, in the US romiplostim is only approved for weekly administration by a healthcare provider (HCP) using an 0.01 mL graduation syringe to ensure dosing accuracy; a dose tolerance margin of romiplostim has never been investigated before. The following work explores the impact of dosing tolerance on PC to assess the feasibility of romiplostim self-administration in adult ITP patients.Methods: The analysis was based on a previously developed pharmacodynamic model of romiplostim in ITP patients (Perez-Ruixo et al, 2012, Gibiansky et al, 2021). Previous romiplostim clinical studies in patients with ITP were leveraged to develop an updated model of 475 ITP patients (>50 kg, weekly romiplostim total dose > 100 µg and between 1 and 10 µg/kg stable maintenance dose for at least 1 month, self-administration) and assess potential differences in PC between ITP patients who qualify for self-administration and the general adult ITP population. Comparison of observed and model predicted PC and romiplostim dose over time confirmed the adequacy of the model to assess the impact of varying dose tolerances on PC that may occur with self-administration.Under the proposed guidelines for romiplostim self-administration eligibility, an adult patient would self-administer up to 4 weekly stable maintenance doses of romiplostim between two platelet measurements 1 month apart. To evaluate the impact on PC over 1 month when patients self-administered all four weekly doses versus patients receiving the same prescribed dose by a healthcare provider, three dosing scenarios were considered: (1) exact titrated dose (no dose deviation), (2) titrated dose plus 0.03 mL or 15 µg of romiplostim, and (3) titrated dose minus 0.03 mL or 15 µg of romiplostim. To further characterize the number of ITP patients with clinically meaningful platelet deviations, the predicted number of virtual patients with a PC below 30 x10 9/L or above 400 x10 9/L were also summarized for each simulated scenario.Lastly, the simulated population was divided into four groups based on the magnitude of their prescribed dose and used to evaluate whether the prescribed romiplostim dose influences platelet excursion rates following the investigated dose scenarios.Results: Simulations suggest that 4 successive weekly doses of ± 0.03 mL (or ± 15 µg) the prescribed romiplostim dose is unlikely to cause a significant change in platelet excursion rates relative to continuous administration of the exact prescribed dose. No meaningful increase (0.1 - 0.4%) was observed in the predicted excursion rates across these thresholds for either the under- or overdosing scenarios (Figure 1).This results also show that while there is a slight trend between the magnitude of the prescribed dose and the fraction of subjects that experience a platelet excursion, it does not result in a meaningful increase (<4%) in platelet excursions in any of the evaluated subgroups. Specifically, we observed minimal changes in the fraction of patients with a platelet excursion outside the potentially clinically meaningful thresholds across all simulated dose groups and dosing scenarios (Table 1).The results from this analysis suggest that possible dosing variance expected from the self-administration of romiplostim by an eligible lay person (± 0.03 mL or 15 μg) with monthly PC evaluation will not lead to a significant increase in the rate of platelet count excursions for patients who achieve a stable romiplostim dose and meet the proposed eligibility criteria. [Display omitted] DisclosuresSerrano Castillo: Amgen: Current Employment, Current equity holder in publicly-traded company. Saad: Amgen: Current Employment, Current equity holder in publicly-traded company. Wang: Amgen Inc: Current Employment, Current equity holder in publicly-traded company. Zhang: Amgen: Current Employment, Current equity holder in publicly-traded company. Chow: Amgen: Current Employment, Current equity holder in publicly-traded company. Doshi: Amgen: Current equity holder in publicly-traded company; Amgen: Current Employment.

Statistical Method for Trending of Excursions in Clean Room Microbiological Monitoring Data.

A statistically robust set of rules is proposed for trending excursions in environmental monitoring data. These rules were designed to minimize false alarms when the process is in control, but signal quickly when the process goes out of control. An adverse trend is an early warning that the system is drifting from normal operating conditions. Prompt action may prevent further deterioration and avoid costly out-of-specification events. Adverse trends are defined as an alert level excursion rate of >2.5% and an action level excursion rate of >0.15%. These definitions were derived from setting action levels at the 99.85th percentile and alert levels at the 97.5th percentile. These percentiles were chosen because they are functional equivalents of control limits and warning limits used in statistical process control charting, which are set at three and two standard deviations above the mean, respectively. In addition, the U.S. Pharmacopeial recommended microbial recovery rates should also be implemented as trend metrics for microbial environmental monitoring of aseptic processing facilities. Occasional isolated alert level excursions may occur even if the process remains in a state of control. However, repeated alert level excursions occurring at a rate >2.5% indicate the process is changing and the system is drifting from normal operating conditions. An adverse trend of alert level excursions should be investigated for root cause. It is critical to determine if an alert level excursion, at its onset, indicates an adverse trend. A total of 24 rules at various sample sizes were tested for their ability to detect an adverse trend at the onset of an excursion using data obtained over a period of 1 year. The rationale for choosing these rules is described.

Shrinking targets for the geodesic flow on geometrically finite hyperbolic manifolds

&lt;p style='text-indent:20px;'&gt;Let &lt;inline-formula&gt;&lt;tex-math id="M1"&gt;\begin{document}$ \mathscr{M} $\end{document}&lt;/tex-math&gt;&lt;/inline-formula&gt; be a geometrically finite hyperbolic manifold. We present a very general theorem on the shrinking target problem for the geodesic flow, using its exponential mixing. This includes a strengthening of Sullivan's logarithm law for the excursion rate of the geodesic flow. More generally, we prove logarithm laws for the first hitting time for shrinking cusp neighborhoods, shrinking tubular neighborhoods of a closed geodesic, and shrinking metric balls, as well as give quantitative estimates for the time a generic geodesic spends in such shrinking targets.&lt;/p&gt;

Indicators of external respiratory system of people aged 50-55 during ethnical games of the kyrgyz people in the middle mountains region

Ethnical outdoor games affect all muscle groups and have a positive effect on respiratory system. When studying indicators of external respiratory system (chest excursion, lungs capacity, respiratory rate, Stange and Genchi tests), we can assess the impact of ethnic outdoor games on human body. Purpose: to reveal improvement of indicators of the respiratory system of people aged 50-55 during ethnical games of Kyrgyz people in the middle mountains region. Research methods and organization. The analysis of scientific and methodical literature was carried out with the use of the following methods: physiometry (chest excursion, lungs capacity, respiratory rate); specific breathing tests (Stange and Genchi tests); mathematic and statistical methods. The significance of difference between the homogeneous indicators was assessed in accordance with the critical value of Student t-criterion. Research results and discussion. The study resulted in identification of average statistical indicators and indicators of the significance of difference in chest excursion, lungs capacity, respiratory rate, Stangе and Genchi test outcomes of men and women practicing ethnic outdoor games and modern techniques of physical activity. Conclusion. Comparative analysis of the data obtained from two surveys demonstrated significant improvement of the indicators of chest excursion, lungs capacity and respiratory rate of men and women practicing ethnical outdoor games. Respiratory tests revealed a significant increase in the functional reserve of the respiratory system of men and women in both groups. In terms of the Stange test, there was significant difference in favor of the 2nd survey. According to the results of the Genchi test, the 2nd examination showed certain increase for men and significant increase for women.

Rate of torque development is the primary contributor to quadriceps avoidance gait following total knee arthroplasty

BackgroundFollowing rehabilitation for total knee arthroplasty, “quadriceps avoidance gait”, defined by limited knee flexion angle excursion during walking, persists and contributes to poor long-term outcomes. Given the presence of several post-surgical impairments, identifying the contribution of multiple factors to knee flexion angle excursion is important to developing targeted interventions to improve recovery after total knee arthroplasty. Research questionsWhich outcomes continue to improve following rehabilitation for total knee arthroplasty? What are the primary contributors to impaired knee flexion angle excursion during walking following total knee arthroplasty? MethodsPeak muscle strength and rate of torque development of the quadriceps, hip abductors, and hip external rotators, five-time sit-to-stand test, Knee Injury & Osteoarthritis Outcome Score, and gait mechanics were assessed in 24 participants at three and six months post-surgery. Paired sample t-tests or Wilcoxon Signed-Rank tests were used to compare outcomes between assessments. Stepwise multiple linear regression were used to assess the contribution of each measure to knee flexion angle excursion. ResultsSignificant improvements were noted in all outcomes except hip external rotation rate of torque development, gait speed, and knee flexion angle excursion. Quadriceps rate of torque development and knee pain significantly contributed to knee flexion angle excursion at three months (Adjusted R2 = 0.342), while quadriceps rate of torque development and peak hip external rotation strength significantly contributed at six months (Adjusted R2 = 0.436). SignificanceWhile higher pain levels at three months and greater peak hip external rotation muscle strength at six months contribute to impaired knee flexion angle excursion, quadriceps rate of torque development was the primary contributor to knee flexion angle excursion at both three and six months after surgery. Implementing strategies to maximize quadriceps rate of torque development during rehabilitation may help to reduce quadriceps avoidance gait after total knee arthroplasty.

Sample Path Large Deviations for Stochastic Evolutionary Game Dynamics

We study a model of stochastic evolutionary game dynamics in which the probabilities that agents choose suboptimal actions are dependent on payoff consequences. We prove a sample path large deviation principle, characterizing the rate of decay of the probability that the sample path of the evolutionary process lies in a prespecified set as the population size approaches infinity. We use these results to describe excursion rates and stationary distribution asymptotics in settings where the mean dynamic admits a globally attracting state, and we compute these rates explicitly for the case of logit choice in potential games.

Challenges of cold chain quality for routine EPI in south-west Burkina-Faso: An assessment using automated temperature recording devices

BackgroundAbnormal temperatures are a major issue for vaccines within the Expanded Program of Immunization in tropical climates. Prolonged exposure to temperatures outside the standard +2 °C/+8 °C range can impact vaccine potency. MethodsThe current study used automatic temperature recording devices (Testostore 171-1©) to monitor cold chain in remote areas of Western Burkina Faso. A series of 25 randomly selected health centers representing 33% of the existing 176 EPI facilities in Western Burkina Faso were prospectively assessed for eight months in 2015. Automatic measurements were compared to routine temperature loggers and vaccine vial monitors (VVM). ResultsThe median age for all refrigerators was 9 years with 10/25 (42%) older than 10 years. Adverse temperatures were recorded in 20/24 (83%) refrigerators and ranged from −18.5 °C to +34.2 °C with 12,958/128,905 (10%) abnormal hourly records below +2 °C and 7357/128,905 (5.7%) above +8 °C. Time of day significantly affected the rate of temperature excursions, with higher rates from 00 am to 06 am (p < 0.001) for low temperatures and 10–12 am (p < 0.001) and 13–16 pm (p < 0.001) for high temperatures. Abnormal temperatures lasted from 1 h to 24 h below +2 °C and 13–24 h above +8 °C. Standard manual registers reported only 182/2761 (7%) inadequate temperatures and VVM color change detected only 133/2465 (5%) disruptions. Reliability of the refrigerators ranged from 48% to 98.7% with a median of 70%. Risk factors for excursions were old age of the refrigerators, the months of April and May, hours of high activity during the day, and health staff-associated factors such as inappropriate actions or insufficient knowledge. ConclusionImportant cold chain reliability issues reported in the current study in Western Burkina Faso raise concern about vaccine potency. In the absence of systematic renewal of the cold chain infrastructure or improved staff training and monitoring, antibody response assessment is recommended to study levels of effective immunization coverage.

Joint kinematics and ground reaction forces in overground versus treadmill graded running

BackgroundTreadmills are often used to assess running biomechanics, however the validity of applying results from treadmill graded running to overground graded running is currently unknown. Research questionThe purpose of this study was to investigate whether treadmill and overground graded running have comparable kinematics and ground reaction force parameters. MethodsEleven healthy male adults ran overground and on an instrumented treadmill as motion capture and force platform data were collected for the following conditions: downhill running at a slope of −8° at 10, 13 and 16 km⋅h−1; level running at 10 and 13 km⋅h−1; uphill running at a slope of +8° at 8, 10 and 13 km⋅h−1. Sagittal joint angles at heel strike, mid-stance, and toe-off were computed for the ankle, knee and hip. Ground reaction force parameters including peak average and instantaneous normal loading rate, peak impact and active normal force, peak tangential (braking and propulsive) forces, and normal and tangential impulses were also calculated. ResultsJoint kinematics and ground reaction forces for level running were generally similar between overground and treadmill conditions. The following variables were significantly higher during overground uphill running (mean difference ± SD): average normal loading rate (14.4 ± 7.1 BW⋅s−1), normal impulse (0.04 ± 0.02 BW⋅s), propulsive impulse (0.04 ± 0.02 BW⋅s), and vertical center of mass excursion (0.092 ± 0.031 m). The following variables were significantly higher during overground downhill running (mean difference ± SD): ankle plantarflexion at toe-off (−5.39 ± 6.19°) and vertical center of mass excursion (0.046 ± 0.039 m). SignificanceThese findings suggest that subtle differences in kinematics and ground reaction forces exist between overground and treadmill graded running. These differences aside, we believe that overground kinematics and ground reaction forces in graded running are reasonably replicated on a treadmill.

Coordinated Operation and Control of Combined Electricity and Natural Gas Systems with Thermal Storage

As one of the most effective approaches in dealing with the energy crisis, combined electricity and natural gas systems have become more and more popular worldwide. To take full advantages of such hybrid energy networks, a proper operation and control method is required. In this paper, a novel approach coordinating combined heating and power generation is proposed. First, state excursion rate, a criterion describing the deviation of system operation, is defined for system state evaluation. Then, thermal energy storage is allocated to provide more and better operation modes for combined generation. By investigating the state excursion rate of hybrid energy systems, the optimal operation mode is chosen through an analytical strategy. Case studies on hybrid energy networks show that all state variables, including voltages in electric systems and pressures in gas networks, are adjusted to follow proper operation constraints by the implementations of the proposed strategy. In addition to providing sufficient auxiliary services for hybrid systems, it is also possible to maintain the economic and energy-efficient benefits of energy supply. This study provides an effective method to utilize the regulation capability of combined heating and power generations, which is a technical basis of energy internet.

Combined Oral Administration of GABA and DPP-4 Inhibitor Prevents Beta Cell Damage and Promotes Beta Cell Regeneration in Mice.

γ-aminobutyric acid (GABA) or glucagon-like peptide-1 based drugs, such as sitagliptin (a dipeptidyl peptidase-4 inhibitor), were shown to induce beta cell regenerative effects in various diabetic mouse models. We propose that their combined administration can bring forth an additive therapeutic effect. We tested this hypothesis in a multiple low-dose streptozotocin (STZ)-induced beta cell injury mouse model (MDSD). Male C57BL/6J mice were assigned randomly into four groups: non-treatment diabetic control, GABA, sitagliptin, or GABA plus sitagliptin. Oral drug administration was initiated 1 week before STZ injection and maintained for 6 weeks. GABA or sitagliptin administration decreased ambient blood glucose levels and improved the glucose excursion rate. This was associated with elevated plasma insulin and reduced plasma glucagon levels. Importantly, combined use of GABA and sitagliptin significantly enhanced these effects as compared with each of the monotherapies. An additive effect on reducing water consumption was also observed. Immunohistochemical analyses revealed that combined GABA and sitagliptin therapy was superior in increasing beta cell mass, associated with increased small-size islet numbers, Ki67+ and PDX-1+ beta cell counts; and reduced Tunel+ beta cell counts. Thus, beta cell proliferation was increased, whereas apoptosis was reduced. We also noticed a suppressive effect of GABA or sitagliptin on alpha cell mass, which was not significantly altered by combining the two agents. Although either GABA or sitagliptin administration delays the onset of MDSD, our study indicates that combined use of them produces superior therapeutic outcomes. This is likely due to an amelioration of beta cell proliferation and a decrease of beta cell apoptosis.

Evaluating gain functions in foraging bouts using vertical excursions in northern elephant seals

The marginal value theorem models patch departure decisions for foraging animals when resources are unevenly distributed. A key component of these models is the decelerating energy gain function used to represent patch depletion. However, the within-patch gain function has rarely been assessed in marine predators. We evaluated the gain functions in foraging bouts of northern elephant seals, Mirounga angustirostris, using a long-term data set (2004–2012) that included complete foraging trips from 205 individual female northern elephant seals on 303 migrations as revealed by time–depth recorders and satellite tags (Argos System Inc.). Since the majority of putative prey capture attempts are associated with vertical excursions at the bottom of dives, we used vertical excursions to evaluate patch depletion across foraging bouts as defined using dive shapes. Rates of energy gain were measured using changes in mass and body composition across trips. Decelerating gain functions occurred in 83% of 77 820 foraging bouts, with the remainder showing accelerating functions. Rates of patch depletion strongly influenced patch residence times. Despite wide variation between individual patches, mean deceleration exponents did not vary with year or season, suggesting that average rates of patch depletion were relatively stable across the study period. The mean duration and number of dives in foraging bouts showed little annual or seasonal variation; however, the mean rate of vertical excursions during foraging dives varied and predicted rates of energy gain across migrations. The relative mean consistency of individual diving behaviour despite wide variation in geoposition supports the idea that northern elephant seals have evolved a foraging strategy that buffers against short-term variation in prey abundance and optimizes energy acquisition across the duration of the migration.

Dexmedetomidine for Refractory Intracranial Hypertension.

Dexmedetomidine (DEX) is a selective α2 adrenergic agonist that is commonly used for sedation in the intensive care unit (ICU). The role of DEX for adjunctive treatment of refractory intracranial hypertension is poorly defined. The primary objective of this study was to determine the effect of DEX on the need for rescue therapy (ie, hyperosmolar boluses, extraventricular drain [EVD] drainages) for refractory intracranial hypertension. Secondary objectives included the number of intracranial pressure (ICP) excursions, bradycardic, hypotensive, and compromised cerebral perfusion pressure episodes. This retrospective cohort study evaluated patients admitted to the neurosurgical ICU from August 1, 2009, to July 29, 2015, and who received DEX for refractory intracranial hypertension. The objectives were compared between the 2 time periods-before (pre-DEX) and during therapy (DEX). Twenty-three patients with 26 episodes of refractory intracranial hypertension met the inclusion criteria. The number of hyperosmolar boluses was decreased after DEX therapy was initiated. Mannitol boluses required were statistically reduced (1 vs 0.5, P = .03); however, reduction in hypertonic boluses was not statistically significant (1.3 vs 0.9, P = .2). The mean number of EVD drainages per 24 hours was not significantly different between the time periods (15.7 vs 14.0, P = .35). The rate of ICP excursions did not differ between the 2 groups (24.3 vs 22.5, P = .62). When compared to pre-DEX data, there was no difference in the median number of hypotensive (0 vs 0), bradycardic (0 vs 0), or compromised cerebral perfusion pressure episodes (0.5 vs 1.0). Dexmedetomidine may avoid increases in the need for rescue therapy when used as an adjunctive treatment of refractory intracranial hypertension without compromising hemodynamics.

PP.33.14] TEI INDEX AS A TOOL FOR THE DIAGNOSIS OF LEFT VENTRICULAR DYSFUNCTION WITH PRESERVED EJECTION FRACTION IN HYPERTENSIVE PATIENTS

Objective: The frequency of left ventricular dysfunction (LVD) in patients (p) with hypertension (HBP) and the methodologies used for its detection are controversial issues. The Ventricular Performance Index, known as Tei index, simultaneously evaluates systolic and diastolic function, and could be a useful tool in HBP p with preserved ejection fraction (PEF). To determine the frequency of LVD in HBP p with PEF by Tei Index. Design and method: Case – control study. Patients divided in three groups: 1) HBP p without left ventricular hypertrophy (LVH); 2) HBP with LVH; 3) non-HBP controls. Volumetric >54% was considered PEF. Left ventricular mass index was measured by Devereux method, LVH was considered with values >95 g/m2 in women and >115 g/m2 in men. Transmitral diastolic peak early flow to septal/lateral mitral annulus average peak early diastolic velocities (E/e’ ratio). Systolic and diastolic functions were assessed by standard echocardiography and tissue Doppler and measured as the average diastolic excursion rate of the septal and lateral walls at the mitral annulus level in diastole (e’ wave) and systole (s wave). Left atrial volume index (LAVI) was measured. 2013 ESH / ESC Hypertension Guidelines cutoff values were considered. Tei index was measured at the lateral and septal walls of the left ventricle in the apical 4-chamber view by tissue Doppler, three measurements of isovolumetric contraction time, ejection time, and isovolumic relaxation time were averaged and a value >0.40 was considered abnormal. Statistical analysis: ANOVA test, p < 0.05 was considered statistically significant. Results: The mean sample age was 57.3+14.5 years, 54.2 % p were males. 88 non LVH HBP p; 19 LVH HBP p; and 11 non-HBP controls were included. Table shows systolic and diastolic left ventricular function results:Conclusions: 1) abnormal left ventricular function is frequent in HBP p, even in the absence of LVH; 2) tissue Doppler obtained Tei Index is a useful tool for the diagnosis of LVD.