Continuous Interval Research Articles

Erratum to: Moderate intensity continuous and high intensity interval training as strategy cardioprotective on cardiotoxicity induced by cancer. Randomized clinical trial.

Erratum to: Moderate intensity continuous and high intensity interval training as strategy cardioprotective on cardiotoxicity induced by cancer. Randomized clinical trial.

Research on Distribution Network Topology Identification Algorithm Based on Mutual Information Bayesian Network

In this paper, a distribution network topology identification algorithm based on mutual information Bayesian network is proposed. In this algorithm, the Bayesian model is mainly used to fit the nonlinear relationship among various variables such as photovoltaic, load, measured voltage, and distribution network topology. Then, the mutual information network is used to effectively divide the measurement continuous stage intervals of variables, thus improving the identification and analysis accuracy of the distribution network topology by Bayesian network, and solving the problems existing in traditional Bayesian network applications, such as difficult continuous data processing, poor adaptability of many continuous deformations, etc.

Should responder analyses be conducted on continuous outcomes?

Continuous outcomes are often dichotomized to classify trial subjects as responders or nonresponders, with the difference in rates of response between treatment and control defined as the "responder effect." In this article, we caution that dichotomization of continuous interval outcomes may not be best practice. Defining clinical benefit or harm for continuous interval outcomes as the difference between the means of treatment and control, that is, the "continuous treatment effect," we examine the case where treatment and control outcomes are normally distributed and differ only in location. For this case, continuous treatment effects may be considered clinically relevant if they exceed a prespecified minimum clinically important difference. In contrast, using minimum clinically important differences as dichotomization thresholds will not ensure clinically relevant responder effects. For example, in some situations, increasing the threshold may actually relax the criterion for effectiveness by increasing the calculated responder effect. Using responder effects to quantitatively assess benefit or risk of investigational drugs for continuous interval outcomes presents interpretational challenges. In particular, when the dichotomization threshold is halfway between the treatment and control outcome means, the responder effect is at a maximum with a magnitude monotonically related to the number of standard deviations between the mean outcomes of treatment and control. Large responder effect benefits may therefore reflect clinically unimportant continuous treatment effects amplified by small standard deviations, and small responder effect risks may reflect either clinically important continuous treatment effects minimized by large standard deviations, or selection of a dichotomization threshold not providing maximum responder effect.

Assessing the nature of premature responses in the rodent continuous performance test variable intertrial interval schedule using atomoxetine and amphetamine

BackgroundRodent operant tests that include premature responses (PR) as a measure of impulsivity commonly use variable intertrial interval (vITI) schedules. The rodent continuous performance test (rCPT) is suitable for a vITI schedule. New MethodWe optimised the analysis for a rCPT vITI schedule with intertrial intervals (ITIs) of 3, 6, and 12 s. Examining the nature of first (FiT) and following touches (FoT) to the blank screen led to a separate quantification of these two behaviours into the first touches level (%FiT) and the following-to-first touches ratio (FoT/FiT). ResultsFiTs occurred more frequently in the 12 s ITIs than at shorter ITIs. Within 12 s ITIs, %FiT was only moderately higher during the last half than the first half, suggesting that long ITIs have a minimal effect on impulsivity, but allow a longer time for its detection. %FiT and the FoT/FiT ratio were uncorrelated. %FiT was negatively correlated with response criterion (C) and uncorrelated with discriminability. Conversely, FoT/FiT ratio was negatively correlated with discriminability, without correlation to C. Atomoxetine decreased %FiT but did not affect FoT/FiT ratio. Amphetamine increased %FiT and decreased the FoT/FiT ratio. Comparison with Existing Method(s)The results suggest that %FiT is analogous to %PR in related tasks and is a more suitable measure of waiting impulsivity in the rCPT. FoT/FiT ratio is unrelated to %FiT. ConclusionsLong ITIs increase the detectability of, but has minimal effect on, waiting impulsivity. %FiT is analogous to %PR in related tasks, while the FoT/FiT ratio is a separate behaviour requiring further characterization.

Erythroid Response in Patients with Non-Transfusion-Dependent β-Thalassemia Treated with Luspatercept: Long-Term Data from the BEYOND Trial

Introduction: Long-term, untreated anemia in patients with non-transfusion-dependent (NTD) β-thalassemia can lead to serious clinical complications. Several studies have shown that increasing hemoglobin (Hb) levels by ≥ 1 g/dL can significantly decrease the risk of developing morbidities (Musallam KM, et al. Ann Hematol 2022;101:203-204; Musallam KM, et al. Ann Hematol 2021;100:1903-1905). Although there are no available treatments for NTD β-thalassemia-associated anemia, previous studies showed that luspatercept improved erythropoiesis leading to a decrease in transfusion burden in pts with transfusion-dependent β-thalassemia, and durably increased Hb levels in pts with NTD β-thalassemia (Cappellini MD, et al. N Engl J Med 2020;382:1219-1231; Taher AT, et al. HemaSphere 2021;5[Suppl 2]. Abstract S101). Here, we report the long-term efficacy update of luspatercept in patients with NTD β-thalassemia in the BEYOND trial (NCT03342404). Methods: Eligible patients (N = 145) with NTD β-thalassemia or HbE/β-thalassemia (defined as receiving 0-5 RBC units in the 24 weeks [wk] prior to randomization) and Hb levels ≤ 10 g/dL were randomized to luspatercept (1.0-1.25 mg/kg) or placebo subcutaneously for ≥ 48 wk. Assessment groups were based on patient assignment at randomization: patients in the luspatercept arm were assessed while remaining on treatment and patients in the placebo arm were assessed up to discontinuation or crossover to luspatercept. Mean change from baseline in Hb was assessed for continuous 12-wk intervals up to wk 144. Erythroid response was defined as mean Hb change from baseline of ≥ 1 g/dL and was assessed over rolling 12-wk intervals. The incidence of RBC transfusions (events and units) was also assessed. Results: As of September 22, 2021, 83 (86.5%) patients in the luspatercept arm and 16 (32.7%) in the placebo arm completed ≥ 96 wk of treatment. Moreover, 72 (75.0%) patients in the luspatercept arm completed ≥ 120 wk of treatment. The median (range) treatment duration was 150.1 (15.0-185.4) wk in the luspatercept arm and 61.1 (3.0-138.0) wk in the placebo arm. Patients in the luspatercept and placebo arms received a median (range) of 42.0 (3.0-61.0) doses and 20.0 (1.0-46.0) doses per patient, respectively. Mean (standard error [SE]) Hb change from baseline in the luspatercept arm was 1.28 (0.069) g/dL during wk 1-12 and 1.48 (0.078) g/dL during wk 13-24, and the increase was maintained among patients remaining on study through all time points. Improvements in Hb levels from baseline were nominally significant versus placebo at assessed 12-wk intervals up to wk 96 (Figure). The proportion of patients experiencing an erythroid response during any 12-wk interval increased from 91.7% (88/96 patients) at the primary data cutoff date (September 14, 2020), to 93.8% (90/96 patients) at the current data cutoff date. Among responders, the proportion of patients in the luspatercept arm with more than one 12-wk rolling response increased from 35.2% (31/88 patients) to 61.1% (55/90 patients) between the primary and current data cutoff dates, and the mean (standard deviation [SD]) total duration of erythroid response among patients with at least one 12-wk rolling response also increased, from 611.1 (243.3) to 873.1 (363.4) days. During wk 1-96, a smaller proportion of patients in the luspatercept arm compared to the placebo arm (10.4% [10/96 patients] vs 32.7% [16/49 patients]) had ≥ 2 RBC transfusions. During the same period, the mean number of transfusion events (0.4 vs 1.3) and RBC units transfused (0.7 vs 2.2) per patient was lower in the luspatercept arm than in the placebo arm. During wk 97-144, the mean number of transfusion events and units per patient in the luspatercept arm remained stable (0.2 events and 0.2 units, respectively). Conclusions: Long-term luspatercept treatment resulted in sustained and significantly improved Hb levels in patients with NTD β-thalassemia. The duration of erythroid response increased with an additional year of luspatercept treatment. Few patients required RBC transfusions and the cumulative incidence of RBC transfusions remained low and relatively stable through 144 wk. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Omics Markers of Red Blood Cell Transfusion in Trauma.

Red blood cell (RBC) transfusion is a life-saving intervention for millions of trauma patients every year worldwide. While hemoglobin thresholds are clinically driving the need for RBC transfusion, limited information is available with respect to transfusion efficacy at the molecular level in clinically relevant cohorts. Here, we combined plasma metabolomic and proteomic measurements in longitudinal samples (n = 118; up to 13 time points; total samples: 690) from trauma patients enrolled in the control of major bleeding after trauma (COMBAT) study. Samples were collected in the emergency department and at continuous intervals up to 168 h (seven days) post-hospitalization. Statistical analyses were performed to determine omics correlate to transfusions of one, two, three, five, or more packed RBC units. While confounded by the concomitant transfusion of other blood components and other iatrogenic interventions (e.g., surgery), here we report that transfusion of one or more packed RBCs—mostly occurring within the first 4 h from hospitalization in this cohort—results in the increase in circulating levels of additive solution components (e.g., mannitol, phosphate) and decreases in the levels of circulating markers of hypoxia, such as lactate, carboxylic acids (e.g., succinate), sphingosine 1-phosphate, polyamines (especially spermidine), and hypoxanthine metabolites with potential roles in thromboinflammatory modulation after trauma. These correlations were the strongest in patients with the highest new injury severity scores (NISS > 25) and lowest base excess (BE < −10), and the effect observed was proportional to the number of units transfused. We thus show that transfusion of packed RBCs transiently increases the circulating levels of plasticizers—likely leaching from the blood units during refrigerated storage in the blood bank. Changes in the levels of arginine metabolites (especially citrulline to ornithine ratios) are indicative of an effect of transfusion on nitric oxide metabolism, which could potentially contribute to endothelial regulation. RBC transfusion was associated with changes in the circulating levels of coagulation factors, fibrinogen chains, and RBC-proteins. Changes in lysophospholipids and acyl-carnitines were observed upon transfusion, suggestive of an effect on the circulating lipidome—though cell-extrinsic/intrinsic effects and/or the contribution of other blood components cannot be disentangled. By showing a significant decrease in circulating markers of hypoxia, this study provides the first multi-omics characterization of RBC transfusion efficacy in a clinically relevant cohort of trauma patients.

Continuous Glucose Deviation Interval and Variability Analysis (CG-DIVA): A Novel Approach for the Statistical Accuracy Assessment of Continuous Glucose Monitoring Systems.

The accuracy of continuous glucose monitoring (CGM) systems is crucial for the management of glucose levels in individuals with diabetes mellitus. However, the discussion of CGM accuracy is challenged by an abundance of parameters and assessment methods. The aim of this article is to introduce the Continuous Glucose Deviation Interval and Variability Analysis (CG-DIVA), a new approach for a comprehensive characterization of CGM point accuracy which is based on the U.S. Food and Drug Administration requirements for "integrated" CGM systems. The statistical concept of tolerance intervals and data from two approved CGM systems was used to illustrate the CG-DIVA. The CG-DIVA characterizes the expected range of deviations of the CGM system from a comparison method in different glucose concentration ranges and the variability of accuracy within and between sensors. The results of the CG-DIVA are visualized in an intuitive and straightforward graphical presentation. Compared with conventional accuracy characterizations, the CG-DIVA infers the expected accuracy of a CGM system and highlights important differences between CGM systems. Furthermore, it provides information on the incidence of large errors which are of particular clinical relevance. A software implementation of the CG-DIVA is freely available (https://github.com/IfDTUlm/CGM_Performance_Assessment). We argue that the CG-DIVA can simplify the discussion and comparison of CGM accuracy and could replace the high number of conventional approaches. Future adaptations of the approach could thus become a putative standard for the accuracy characterization of CGM systems and serve as the basis for the definition of future CGM performance requirements.

Earning While Learning: An Adversarial Multi-Armed Bandit Based Real-Time Bidding Scheme in Deregulated Electricity Market

As the specific incarnation of cyber-physical-social systems, in deregulated electricity market, the market gaming behaviors may have significantly affected the costs of electricity delivered to the market. Especially, from the supply side, the primary goal of power generating companies (PGCs) is to develop strategic biddings to maximize their profits in long-term trading, when facing intrinsic uncertainty. Typically, in such repeated and dynamic settings, one fundamental challenge is that, any PGC neither has prior knowledge about all unknown opponents’ incentives, nor observes their strategies and obtained profits. Especially, the common setting is that, once the bidding auction has occurred, the PGC only observes the market clearing price (MCP) at each round, and winning or losing status. While it is typical to assume some perfect or bounded rationality model of the PGCs, their real behaviors do not follow such assumptions due to lack of complete information, computational intractability, or lack of perfect execution, etc. We formulate the problem of sequentially optimizing any PGC's bids with an adversarial multi-armed bandit (MAB) model. Specifically, at each round, a PGC chooses to play against all other opponents from an infinite set of possible strategies that are split into continuous intervals by sequentially occurred MCPs. Then at the end of each round, the PGC observes the outcome of the auction and updates its estimation on the expected bid's fitness for each interval (i.e., how much the expected profit of the interval could be achieved), and selects the bid for the next round using the proposed algorithm Exp3C (i.e., exponential-weight for exploration and exploitation with continuous value). The experimental results based on real dataset demonstrate that Exp3C performs better than other heuristic schemes including pure greedy, <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${\boldsymbol{\varepsilon}}$</tex-math></inline-formula> -greedy and MCP predication based bidding schemes. Moreover, we theoretically prove the upper bound of average Exp3C regret per round follows <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${\boldsymbol{O}} ({2/\sqrt {\boldsymbol{T}} })$</tex-math></inline-formula> , where <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</i> is the number of total rounds. In summary, the proposed Exp3C has two distinguished advantages. First it is distributed, since its decisions uniquely depend on its past decisions and profits. Second, it is rational, since a PGC is given guarantees on its own accumulated profit regardless of other PGCs’ behaviors.

Asymptotic Properties of the Semigroup Generated by a Continuous Interval Map

The article's purpose is twofold. First, we wish to draw attention to the insufficiently known field of continuous-time difference equations. These equations are paradigmatic for modeling complexity and chaos. Even the simplest equation , easily leads to complex dynamics, its solutions are perfectly suited to simulate strong nonlinear phenomena such as large-to-small cascades of structures, intermixing, formation of fractals, etc. Second, in the main body of the article we present a small but very important part of the theory behind the above equation marked by . Just as the discrete-time analog of this equation induces the one-dimensional dynamical system on some interval , so the equation induces the infinite-dimensional dynamical system on the space of functions . In the latter case, not only are the long-term behaviours of solutions critically dependent on the limit behaviour of the sequence (as in the discrete case) but also on the internal structure of as . Assuming to be continuous, we consider the iterations of as the semigroup generated by on the space of continuous maps, and introduce the notion of a limit semigroup for in a wider map space in order to investigate asymptotic properties of . We construct a limit semigroup in the space of upper semicontinuous maps. This enables us to describe both of the aforementioned aspects of our interest around the iterations of .

Prescribing and adjusting exercise training in chronic respiratory diseases – Expert-based practical recommendations

BackgroundInternational guidelines recommend endurance (ET) and strength training (ST) in patients with chronic respiratory diseases (CRDs), but only provide rough guidance on how to set the initial training load. This may unintentionally lead to practice variation and inadequate training load adjustments. This study aimed to develop practical recommendations on tailoring ET and ST based on practices from international experts from the field of exercise training in CRDs. Methods35 experts were invited to address a 64-item online survey about how they prescribe and adjust exercise training. ResultsCycling (97%) and walking (86%) were the most commonly implemented ET modalities. Continuous endurance training (CET, 83%) and interval endurance training (IET, 86%) were the frequently applied ET types. Criteria to prescribe IET instead of CET were: patients do not tolerate CET due to dyspnoea at the initial training session (79%), intense breathlessness during initial exercise assessment (76%), and/or profound exercise-induced oxygen desaturation (59%). For ST, most experts (68%) recommend 3 sets per exercise; 62% of experts set the intensity at a specific load that patients can tolerate for a range of 8 to 15 repetitions per set. Also, 56% of experts advise patients to approach local muscular exhaustion at the end of a single ST set. ConclusionsThe experts´ practices were summarized to develop practical recommendations in the form of flowcharts on how experts apply and adjust CET, IET, and ST in patients with CRDs. These recommendations may guide health care professionals to optimize exercise training programs in patients with CRDs.

Moderate intensity continuous and high intensity interval training as strategy cardioprotective on cardiotoxicity induced by cancer. Randomized clinical trial

Abstract Introduction The adverse physiological consequences of cancer therapy have been recognized for some years. However, Cardio-Oncology aims to detect and manage cardiac dysfunction induced by cancer treatment (Cardiotoxicity) and one of the strategies used is physical exercise, which has shown benefits in cardiovascular fitness in patients with cancer; therefore, this clinical trial has like objective determine the effects cardiovascular of Moderate Intensity Continuous Training (MICT) and High Intensity Interval Training (HIIT) on cardiotoxicity induced for antitumoral treatment. Methodology Randomized controlled trial of 3 years and 4 months with a sample of 753 stage II cancer patients (Prostate cancer, breast, colorectal, thyroid, cervico-uterine, lung, stomach, liver) distributed in 3 groups (MICT, HIIT and control group). Echocardiogram, cardiac biomarkers, stress test, clinical and hemodynamic parameters, risk factors, hematological samples for blood glucose and lipid profile were identified. In addition, 6-minute walk, anthropometry, quality of life, fatigue, sarcopenia, depression, anxiety. The tests were performed before and after 36 session of 70-minute training, 3 times per week. A database was created with results of tests and questionnaires pre and post training. Then, descriptive statistics were carried out to estimate, the normality of the data was assessed by the Kolmogorov-Smirnov test and the indication of specificity was evident for all analyzes. Also, through the Tukey test, the ANOVA analysis of variance (two-way analysis of variance) was used, and subsequently, post hoc tests to assess the characteristics of the different age groups, gender and anthropometry. In all cases, a significance level was 5% (p= &amp;lt;0.05). Results After exercise program, there was an increase in ejection fraction (EG1: 37±3 vs 41±3; EG2: 39±4 vs 47±5; CG: 40±3 vs 40±1; p&amp;lt;0.05). In fact, higher values were observed in Vo2p for experimental group 2-HIIT (7.7±6.4 vs 9.8±3.9) compared to experimental group 1-MICT (8.0±4 vs 8.5±3) and control group (9.0±5.6 vs 9.2±3.9). Likewise, in the values of the systolic blood pressure (139±11 vs 129±2), diastolic blood pressure (86±6 vs 80±1), maximum heart rate (168±11 vs 179±8) and quality of life (109±12 vs 76.5±10). It was possible to show significant changes in all variables of the HIIT and MICT groups (p= &amp;lt;0.05) compared to the control group. Conclusions HIIT and MICT in cancer patients improved the ventricular ejection fraction, hemodynamic parameters, exercise tolerance, depression, anxiety, strength, vo2p, MHR, fatigue associated cancer and others variables like sarcopenia, lipidic profile and quality of life. In fact, it was possible to demonstrate greater benefits of HIIT compared to the MICT and control group. It's noteworthy that the control group without physical training, decreased the vo2 and muscular force and increased the sarcopenia, depression and anxiety. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Centro de Estudios e Investigaciόn FISICOL

Prioritized Safe Interval Path Planning for Multi-Agent Pathfinding With Continuous Time on 2D Roadmaps

We address a challenging multi-agent pathfinding (MAPF) problem for hundreds of agents moving on a 2D roadmap with continuous time. Despite its known potential for producing better solutions compared to typical grid and discrete-time cases, few approaches have been established to solve this problem due to the intractability of collision checks on a large scale. In this work, we propose Prioritized Safe-Interval Path Planning with Continuous-Time Conflicts (PSIPP/CTC) that extends a scalable prioritized planning algorithm to work on the 2D roadmap and continuous-time setup by alleviating intensive collision checks. Our approach involves a novel concept named Continuous-Time Conflict (CTC), which describes a pair among vertices and edges associated with continuous-time intervals within which collisions can happen between agents. We pre-compute CTCs using geometric neighbor-search and sweeping techniques and annotate roadmaps with the CTCs just once before planning starts. Doing so allows us to efficiently enumerate collision-free time intervals for all vertices and edges and find each agent's path with continuous time in prioritized planning. Extensive experimental evaluations demonstrate that PSIPP/CTC significantly outperforms existing methods in terms of planning success rate and runtime while maintaining an acceptable solution quality. As a proof of concept, we also confirmed the effectiveness of the proposed approach on a physics simulation with differential wheeled robots.

An ensemble multi-swarm teaching–learning-based optimization algorithm for function optimization and image segmentation

Intelligent optimization algorithms are widely utilized to deal with complex optimization problems in various areas. However, a single intelligent optimization algorithm cannot handle well more and more complex optimization problems. The ensemble strategy can integrate several different operators and algorithms by using some appropriate strategies and maybe obtain better optimization performance. In this paper, a new ensemble multi-swarm method based on teaching–learning-based optimization (EMTLBO) was proposed by integrating three different algorithms including the original teaching–learning-based optimization algorithm, its variant with neighborhood search and the variant with differential evolution. In EMTLBO, a new evaluating mechanism based on the fitness-based and diversity-based metrics (FDEM) for each sub-swarm was proposed to evaluate the optimization performance after a continuous generation interval. Moreover, an algorithm matching mechanism based on ranking for sub-swarms (AMM) is adapted to re-divide the population into three sub-swarms and match a suitable algorithm for each sub-swarm so as to increase the whole optimization performance. Furthermore, the experimental results on CEC2014 and CEC2017 test suits verify the feasibility and optimization performance of EMTLBO. Finally, the proposed algorithm is extended to optimize the segmentation thresholds of images and the segmentation performances on different benchmark images show that EMTLBO has good performance in most cases.

Skeletal Muscle Mitochondrial and Perilipin Content in a Cohort of Obese Subjects Undergoing Moderate and High Intensity Training.

Obesity is a complex condition characterized by abnormal and excessive fat accumulation, resulting in an increased risk for severe health problems. Skeletal muscles play a major role in movement and fat catabolism, but the insulin resistance that comes with obesity makes it difficult to fulfill these tasks. In this study, we analyse two types of training protocols, moderate intensity continuous training (MICT) versus high intensity interval training (HIIT), in a cohort of obese subjects to establish which muscle adaptations favour fat consumption in response to exercise. Mitochondria play a role in fat oxidation. We found protein upregulation of mitochondrial biomarkers, TOMM20 and Cox-4, in HIIT but not in MICT, without detecting any shifts in fibre composition phenotype of the vastus lateralis in both training groups. Interestingly, both MICT and HIIT protocols showed increased protein levels of perilipin PLIN2, which is involved in the delivery and consumption of fats. HIIT also augmented perilipin PLIN5. Perilipins are involved in fat storage in skeletal muscles and their upregulation, along with the analysis of circulatory lipid profiles reported in the present study, suggest important adaptations induced by the two types of training protocols that favour fat consumption and weight loss in obese subjects.

Serum GFAP- reference interval and preanalytical properties in Danish adults.

Glial fibrillary acidic protein (GFAP) is a promising biomarker that could potentially contribute to diagnosis and prognosis in neurological diseases. The biomarker is approaching clinical use but the reference interval for serum GFAP remains to be established, and knowledge about the effect of preanalytical factors is also limited. Serum samples from 371 apparently healthy reference subjects, 21-90 years of age, were measured by a single-molecule array (Simoa) assay. Continuous reference intervals were modelled using non-parametric quantile regression and compared with traditional age-partitioned non-parametric reference intervals established according to the Clinical and Laboratory Standards Institute (CLSI) guideline C28-A3. The following preanalytical conditions were also examined: stability in whole blood at room temperature (RT), stability in serum at RT and-20°C, repeated freeze-thaw cycles, and haemolysis. The continuous reference interval showed good overall agreement with the traditional age-partitioned reference intervals of 25-136ng/L, 34-242ng/L, and 5-438ng/L for the age groups 20-39, 40-64, and 65-90 years, respectively. Both types of reference intervals showed increasing levels and variability of serum GFAP with age. In the preanalytical tests, the mean changes from baseline were 2.3% (95% CI:-2.4%, 6.9%) in whole blood after 9h at RT, 3.1% (95% CI:-4.5%, 10.7%) in serum after 7days at RT, 10.4% (95% CI:-6.0%, 26.8%) in serum after 133days at-20°C, and 10.4% (95% CI: 9.5%, 11.4%) after three freeze-thaw cycles. The study establishes age-dependent reference ranges for serum GFAP in adults and demonstrates overall good stability of the biomarker.

Moderate continuous or high intensity interval exercise in heart failure with reduced ejection fraction: Differences between ischemic and non-ischemic etiology

BackgroundExercise for heart failure (HF) with reduced ejection fraction (HFrEF) is recommended by guidelines, but exercise mode and intensities are not differentiated between HF etiologies. We, therefore, investigated the effect of moderate or high intensity exercise on left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and maximal exercise capacity (peak VO2) in patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM). MethodsThe Study of Myocardial Recovery after Exercise Training in Heart Failure (SMARTEX-HF) consecutively enrolled 231 patients with HFrEF (LVEF ≤ 35 %, NYHA II-III) in a 12-weeks supervised exercise program. Patients were stratified for HFrEF etiology (ICM versus NICM) and randomly assigned (1:1:1) to supervised exercise thrice weekly: a) moderate continuous training (MCT) at 60–70 % of peak heart rate (HR), b) high intensity interval training (HIIIT) at 90–95 % peak HR, or c) recommendation of regular exercise (RRE) according to guidelines. LVEDD, LVEF and peak VO2 were assessed at baseline, after 12 and 52 weeks. Results215 patients completed the intervention. ICM (59 %; n = 126) compared to NICM patients (41 %; n = 89) had significantly lower peak VO2 values at baseline and after 12 weeks (difference in peak VO2 2.2 mL/(kg*min); p < 0.0005) without differences between time points (p = 0.11) or training groups (p = 0.15). Etiology did not influence changes of LVEDD or LVEF (p = 0.30; p = 0.12), even when adjusting for sex, age and smoking status (p = 0.54; p = 0.12). Similar findings were observed after 52 weeks. ConclusionsEtiology of HFrEF did not influence the effects of moderate or high intensity exercise on cardiac dimensions, systolic function or exercise capacity. Clinical Trial Registration–URLhttp://www.clinicaltrials.gov. Unique identifier: NCT00917046.

The Effect of Eight Weeks of Moderate-Intensity Continuous Training and High Intensity Interval Training along with Citrus aurantium L on some Cardiac Mitochondrial Biogenesis Markers in the Heart Tissue of Elderly Rats

The Effect of Eight Weeks of Moderate-Intensity Continuous Training and High Intensity Interval Training along with Citrus aurantium L on some Cardiac Mitochondrial Biogenesis Markers in the Heart Tissue of Elderly Rats

Comparison of the autonomic nervous system dysfunction between different chronic spine disorders: neck pain versus low back pain.

SUMMARYOBJECTIVE:This study aims to compare heart rate variability (HRV) between patients with chronic neck pain and patients with chronic low back pain and to correlate the chronic pain variables with heart rate variability indices.METHODS:This is a cross-sectional study. We divided the sample into two groups: neck pain (n=30) and low back pain (n=30). We used the Numeric Pain Rating Scale, Neck Disability Index, Roland-Morris Disability Questionnaire, Pain-Related Catastrophizing Thoughts Scale, Tampa Scale of Kinesiophobia, and Pain Self-Efficacy Questionnaire. For heart rate variability analysis, we used the following indices: mean RR, standard deviation of all RR intervals, mean heart rate, root mean square differences of successive RR intervals, triangular index, triangular interpolation of the interval histogram, low-frequency band in arbitrary units and in absolute values, high-frequency band in arbitrary units and in absolute values, standard deviation of the instantaneous beat-to-beat variability (standard deviation 1), long-term standard deviation of continuous RR intervals (standard deviation 2), and Stress Index. We used Student’s t-test for comparisons and Spearman’s coefficient for correlations.RESULTS:We observe insignificant values in the differences between the groups. Disability and self-efficacy were correlated with heart rate variability only in patients with chronic neck pain, whereas catastrophizing and kinesiophobia showed greater correlations with heart rate variability in patients with chronic low back pain.CONCLUSIONS:Autonomic dysfunction of individuals with chronic neck pain, when compared to patients with chronic low back pain, does present insignificant differences.

Luspatercept for the treatment of anaemia in non-transfusion-dependent β-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial

In patients with non-transfusion-dependent β-thalassaemia, haemoglobin concentrations lower than 10 g/dL are associated with a higher risk of morbidity, mortality, and impaired quality of life. No drugs are specifically approved for anaemia management in patients with non-transfusion-dependent β-thalassaemia, other than transfusion therapy administered infrequently in accordance with patients' needs. We assessed the efficacy and safety of luspatercept versus placebo in patients with non-transfusion-dependent β-thalassaemia. We did a phase 2, randomised, double-blind, multicentre, placebo-controlled trial in 12 centres in six countries (Thailand [n=1], Lebanon [n=1], Greece [n=2], Italy [n=5], the UK [n=1], and the USA [n=2]). Eligible patients were aged 18 years or older, had confirmed diagnosis of β-thalassaemia or haemoglobin E/β-thalassaemia (concomitant α-globin deletion, mutation, or duplication were allowed), and a baseline haemoglobin concentration of 10·0 g/dL or lower. All patients were non-transfusion-dependent. Patients were randomly assigned (2:1) to luspatercept or placebo using an interactive response technology system and stratified by baseline haemoglobin concentration (≥8·5 g/dL vs <8·5 g/dL) and baseline Non-Transfusion-Dependent β-thalassaemia-Patient-Reported Outcome Tiredness/Weakness domain score (≥3 vs <3). All patients, study site staff, and sponsor representatives (who reviewed the data), except for designated individuals, were masked to drug assignment until the time the study was unblinded. Luspatercept or placebo was given once subcutaneously every 3 weeks for 48 weeks in the double-blind treatment period. Luspatercept was started at 1·0 mg/kg with titration up to 1·25 mg/kg, or reduction in the event of toxicity or excessive haemoglobin concentration increase. The primary endpoint was achievement of an increase from baseline of 1·0 g/dL or higher in mean haemoglobin concentration over a continuous 12-week interval during weeks 13-24, in the absence of transfusions. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT03342404, and is ongoing. Between Feb 5, 2018, and Oct 14, 2019, 160 patients were screened for eligiblity, of whom 145 were randomly assigned to luspatercept (n=96) or placebo (n=49). 82 (57%) patients were female and 63 (43%) were male. 44 (30%) patients were Asian, 87 (60%) were White, and 14 (10%) identified as another race. The study met its primary endpoint: 74 (77%) of 96 patients in the luspatercept group and none in the placebo group had an increase of at least 1·0 g/dL in haemoglobin concentration (common risk difference 77·1 [95% CI 68·7-85·5]; p<0·0001). The proportion of patients with serious adverse events was lower in the luspatercept group than in the placebo group (11 [12%] vs 12 [25%]). Treatment-emergent adverse events most commonly reported with luspatercept were bone pain (35 [37%]), headache (29 [30%]), and arthralgia (28 [29%]). No thromboembolic events or deaths were reported during the study. Luspatercept represents a potential treatment for adult patients with non-transfusion-dependent β-thalassaemia, for whom effective approved treatment options are scarce. Celgene and Acceleron Pharma.

Formula omitted]-Dimensional Chaotic Map with application in secure communication

When applied to practical applications, existing chaotic systems exhibit many weaknesses, including discontinuous chaotic intervals and easily predicted chaotic signals. This study proposes an n-dimensional chaotic model (nD-CM) to resolve the weaknesses of existing chaotic systems. nD-CM can produce chaotic maps with any desired dimension utilizing existing 1D chaotic maps as seed chaotic maps. To demonstrate the effect of nD-CM, we generate three 2D and one 3D chaotic map as examples, utilizing three 1D chaotic maps as the seed maps. The evaluation and experiment results show that these newly generated chaotic maps can obtain continuous and wider chaotic intervals and better performance using the indicators of the Lyapunov exponent, sample entropy and correlation dimension, compared to existing maps. To further show the practicality of nD-CM, the generated maps are additionally applied to secure communication. The experimental results show that these chaotic maps exhibit much better performance in resisting transmission noise in this application than existing chaotic maps.