Reserve Capacity Research Articles

Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion.

Dual-Interventions targeting glucose and oxidative metabolism are receiving increasing attention in cancer therapy. Sorafenib (S) and Metformin (M), two gold-standards in liver cancer, are known for their mitochondrial inhibitory capacity. Fasting, a glucose-limiting strategy, is also emerging as chemotherapy adjuvant. Herein, we explore the anti-carcinogenic response of nutrient restriction in combination with sorafenib:metformin (NR-S:M). Our data demonstrates that, independently of liver cancer aggressiveness, fasting synergistically boosts the anti-proliferative effects of S:M co-treatment. Metabolic and Cellular plasticity was determined by the examination of mitochondrial and glycolytic activity, cell cycle modulation, activation of cellular apoptosis, and regulation of key signaling and metabolic enzymes. Under NR-S:M conditions, early apoptotic events and the pro-apoptotic Bcl-xS/Bcl-xL ratio were found increased. NR-S:M induced the highest retention in cellular SubG1 phase, consistent with the presence of DNA fragments from cellular apoptosis. Mitochondrial functionality, Mitochondrial ATP-linked respiration, Maximal respiration and Spare respiratory capacity, were all found blunted under NR-S:M conditions. Basal Glycolysis, Glycolytic reserve, and glycolytic capacity, together with the expression of glycogenic (PKM), gluconeogenic (PCK1 and G6PC3), and glycogenolytic enzymes (PYGL, PGM1, and G6PC3), were also negatively impacted by NR-S:M. Lastly, a TMT-proteomic approach corroborated the synchronization of liver cancer metabolic reprogramming with the activation of molecular pathways to drive a quiescent-like status of energetic-collapse and cellular death. Altogether, we show that the energy-based polytherapy NR-S:M blunts cellular, metabolic and molecular plasticity of liver cancer. Notwithstanding the in vitro design of this study, it holds a promising therapeutic tool worthy of exploration for this tumor pathology.

MRI-Based Assessment of Risk for Stroke in Moyamoya Angiopathy (MARS-MMA): An MRI-Based Scoring System for the Severity of Moyamoya Angiopathy.

Before revascularization, moyamoya patients require hemodynamic evaluation. In this study, we evaluated the scoring system Prior Infarcts, Reactivity and Angiography in Moyamoya Disease (PIRAMID). We also devised a new scoring system, MRI-Based Assessment of Risk for Stroke in Moyamoya Angiopathy (MARS-MMA), and compared the scoring systems with respect to the capability to predict impaired [15O]water PET cerebral perfusion reserve capacity (CPR). We evaluated 69 MRI, 69 DSA and 38 [15O]water PET data sets. The PIRAMID system was validated by ROC curve analysis with neurological symptomatology as a dependent variable. The components of the MARS-MMA system and their weightings were determined by binary logistic regression analysis. The comparison of PIRAMID and MARS-MMA was performed by ROC curve analysis. The PIRAMID score correlated well with the symptomatology (AUC = 0.784). The MARS-MMA system, including impaired breath-hold-fMRI, the presence of the Ivy sign and arterial wall contrast enhancement, correlated slightly better with CPR impairment than the PIRAMID system (AUC = 0.859 vs. 0.827, Akaike information criterion 140 vs. 146). For simplified clinical use, we determined three MARS-MMA grades without loss of diagnostic performance (AUC = 0.855). The entirely MRI-based MARS-MMA scoring system might be a promising tool to predict the risk of stroke.

Study on the clinical value of the wearable foetal electrocardiogram monitoring system.

Electronic foetal monitoring (EFM), a method to monitor foetal intrauterine conditions and foetal reserve capacity, is the most extensively used intrauterine monitoring technology in obstetrics. This study aims to compare the Thoth wearable foetal electrocardiogram (foetal ECG [FECG]) monitoring system with a traditional Doppler foetal heart monitoring system before labour to investigate their respective values in clinical application. A total of 393 pregnant women admitted to our hospital between 2020 and 2022 participated in this study. They were recruited using the convenience sampling method. We employed a paired design to assess the confusion rate, trend overlap, and foetal heart rate/ECG monitoring consistency, whereas a completely randomised design was used to measure pregnancy outcome indicators. The participants were divided into two groups using a random number table: the Thoth group (n= 196) and the traditional Doppler group (n= 197). Each group was monitored using the corresponding system. The Thoth monitor demonstrated a lower confusion rate compared with the traditional Doppler monitor (0.25% vs 2.04%; χ2= 5.508, P= 0.019). The trend overlap in foetal heart rates was consistently 100%, with 91.2% of readings showing a consistency rate of ⩾ 95%. Additionally, the Thoth monitor recorded a higher cumulative interruption time in the foetal heart rate curve (12.13 ± 2.22 vs 21.02 ± 2.34; t= 18.471, P< 0.001) and more abnormal ECGs (21.21 ± 4.32 vs 18.21 ± 2.91; t= 7.582, P< 0.001) than the traditional Doppler system. The Thoth wearable FECG monitor offers several advantages over the traditional Doppler foetal heart monitoring system. These include a reduced confusion rate, more accurate data collection, a lower rate of clinical misjudgement, reduced workload for medical staff, and enhanced comfort during vaginal delivery. The rates of emergency caesarean sections and neonatal asphyxia in the Thoth group were marginally lower than those in the Doppler group, which may be attributed to issues such as ECG disconnection or interference from the maternal heart rate.

Coping with drug shortages: A study of government-enterprise option cooperation stockpiling strategies for drugs in shortage considering API surrogate stockpiling subsidies.

Drug shortage is a global problem, and the development of government-enterprise cooperative stockpiles of drugs in shortage, combining physical and production capacity, has become one of the most important means of coping with drug shortages. However, existing studies have tended to overlook the fact that shortages of Active Pharmaceutical Ingredients (APIs) have become an important constraint on production capacity stockpiling and that the lack of incentives and provisions for coordination of benefits have led to a double marginal effect of joint stockpiling by government and enterprises of drugs in shortage. Accordingly, this study introduced the option contract to the drug supply system composed of government and pharmaceutical enterprises and used the subsidy of API storage in lieu as an important initiative to incentivize the reserve of APIs, to construct a model of shortage drug reserve under the government's leadership. This study aims to improve the effect of government-enterprise joint stockpiling of drugs in shortage, which is of great theoretical and practical significance. According to the classification of production license types of pharmaceutical enterprises, this study established a three-level supply chain decentralized decision-making model consisting of the government, formulation enterprises, and API enterprises, and a two-level supply chain centralized decision-making model consisting of the government and API Formulation (API-F) integrated enterprises, respectively. By solving the inverse order derivation, the government-enterprise option cooperation conditions and optimal decision-making strategy were derived. The study results showed that: (i) The addition of enterprise API stockpiling mode can help the government conventional reserves, and enterprise production capacity reserves, broaden the way of drug reserves, and improve the effect of government-enterprise option cooperation; (ii) when the probability of drug shortages is high, the government should prefer the cooperation of API-F integrated enterprises, which is conducive to reducing intermediate links and government costs and improving the supply responsiveness to shortages of medicines; (iii) Setting appropriate government subsidies for API storage can incentivize enterprises to stockpile APIs and improve drug production capacity and physical supply response capability. This study took the problem of socialized stockpiling of drugs in shortage as an entry point and explored the problems and solution strategies in the government-enterprise cooperative stockpiling of drugs in shortage, which not only made some theoretical contributions to the application of options contract in the government-enterprise cooperative stockpiling of drugs in shortage but also provided new ideas and theoretical basis for the improvement of the stockpiling work of drugs in shortage.

Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes.

Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise intolerance remains undefined. We recently demonstrated that the interaction between ARRDC4 (arrestin domain-containing protein 4) and GLUT1 (glucose transporter 1) regulates cardiac metabolism. To determine whether this mechanism broadly impacts diabetic complications, we investigated the role of ARRDC4 in the pathogenesis of diabetic cardiac/skeletal myopathy using cellular and animal models. High glucose promoted translocation of MondoA into the nucleus, which upregulated Arrdc4 transcriptional expression, increased lysosomal GLUT1 trafficking, and blocked glucose transport in cardiomyocytes, forming a feedback mechanism. This role of ARRDC4 was confirmed in human muscular cells from type 2 diabetic patients. Prolonged hyperglycemia upregulated myocardial Arrdc4 expression in multiple types of mouse models of diabetes. We analyzed hyperglycemia-induced cardiac and skeletal muscle abnormalities in insulin-deficient mice. Hyperglycemia increased advanced glycation end-products and elicited oxidative and endoplasmic reticulum stress leading to apoptosis in the heart and peripheral muscle. Deletion of Arrdc4 augmented tissue glucose transport and mitochondrial respiration, protecting the heart and muscle from tissue damage. Stress hemodynamic analysis and treadmill exhaustion test uncovered that Arrdc4-knockout mice had greater cardiac inotropic/chronotropic reserve with higher exercise endurance than wild-type animals under diabetes. While multiple organs were involved in the mechanism, cardiac-specific overexpression using an adenoassociated virus suggests that high levels of myocardial ARRDC4 have the potential to contribute to exercise intolerance by interfering with cardiac metabolism through its interaction with GLUT1 in diabetes. Importantly, the ARRDC4 mutation mouse line exhibited greater exercise tolerance, showing the potential therapeutic impact on diabetic cardiomyopathy by disrupting the interaction between ARRDC4 and GLUT1. ARRDC4 regulates hyperglycemia-induced toxicities toward cardiac and skeletal muscle, revealing a new molecular framework that connects hyperglycemia to cardiac/skeletal myopathy to exercise intolerance.

Determining structural properties of a prestressed concrete bridge through the combination of static and dynamic load testing

Examining structural safety requires hypotheses on several properties of the bridge structure, such as material properties, boundary conditions, and self-weight. The traditional approach relies on conservative assumptions for each structural property, following the conventional new-design approach. Nonetheless, this approach leads to conservative evaluations of the bridge capacity and may lead to the erroneous conclusion that the structure is deficient. Over-conservatism in structural safety assessments may have large environmental and economic impacts on global infrastructure management. A more advanced approach is to conduct multiple tests and monitoring activities on the structural system to provide more accurate values of these bridge properties. This paper presents a methodology to determine several parameters, including the structural stiffness, the boundary conditions, and the self-weight of concrete bridges based on static and dynamic load testing and robust data-interpretation techniques. The methodology is used on a prestressed concrete bridge in Switzerland. This bridge from 1958 has a single span of 35 meters. Prior to monitoring, conservative evaluations (using the conventional approach) led to the conclusion that the bridge has structural deficiencies. After monitoring, the bridge demonstrates significant reserve capacity, mostly due to the reduction of the self-weight safety factor. This study shows the potential of monitoring techniques for more sustainable and economic infrastructure management.

The bearing capacity reserves of steel columns of a single-span frame with a proportional increase in loading history

The bearing capacity reserves of steel columns of a single-span frame with a proportional increase in loading history

Experimental Study of the Flexural Performance of GFRP-Reinforced Seawater Sea Sand Concrete Beams with Built-In GFRP Tubes.

The use of seawater sea sand concrete (SSSC) and fiber-reinforced polymer (FRP) has broad application prospect in island and coastal areas. However, the elastic modulus of FRP reinforcement is obviously lower than that of ordinary steel reinforcement, and the properties of SSSC are different from that of ordinary concrete, which results in a limit in the bearing capacity and stiffness of structures. In order to improve the flexural performance of FRP-reinforced SSSC beams, a novel SSSC beam with built-in glass FRP (GFRP) tubes was proposed in this study. Referring to many large-scale beam experiments, one specimen was used for one situation to illustrate the study considering costs and feasibility. Firstly, flexural performance tests of SSSC beams with GFRP tubes were conducted. Then, the effects of the GFRP tubes' height, the strength grades of concrete inside and outside the GFRP tubes, and the GFRP reinforcement ratio on the flexural behaviors of the beams were investigated. In addition, the concept of capacity reserve was proposed to assess the ductility of the beams, and the interaction between the concrete outside the GFRP tube, the GFRP tube and concrete inside the tube was discussed. Finally, the formulas for the normal section bearing capacity of beams with built-in GFRP tubes were derived and verified. Compared to the beam without GFRP tubes, under the same conditions, the ultimate bearing capacities of the SSSC beam with 80 mm, 100, and 200 mm height GFRP tubes were increased by 17.67 kN, 24.52 kN, and 144.42 kN, respectively.

EAES/SAGES evidence-based recommendations and expert consensus on optimization of perioperative care in older adults

BackgroundAs the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery.MethodsExpert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology.ResultOlder adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery.ConclusionsMIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.

Frailty Syndrome

Frailty is the inability of the body to cope with everyday or acute stressors. The World Health Organization (WHO) defines it as progressive age-related decline in physiological systems that results in decreased reserves of intrinsic capacity. The individual becomes more sensitive to stressors, increasing the likelihood of a general decline in their health (WHO, 2015). Frailty increases the vulnerability of an individual, and the likelihood of hospitalization and death.

Transcriptional profiling of lung macrophages following ozone exposure in mice identifies signaling pathways regulating immunometabolic activation.

Macrophages play a key role in ozone-induced lung injury by regulating both the initiation and resolution of inflammation. These distinct activities are mediated by pro-inflammatory and anti-inflammatory/proresolution macrophages which sequentially accumulate in injured tissues. Macrophage activation is dependent, in part, on intracellular metabolism. Herein, we used RNA-sequencing (seq) to identify signaling pathways regulating macrophage immunometabolic activity following exposure of mice to ozone (0.8 ppm, 3 h) or air control. Analysis of lung macrophages using an Agilent Seahorse showed that inhalation of ozone increased macrophage glycolytic activity and oxidative phosphorylation at 24 and 72 h post-exposure. An increase in the percentage of macrophages in S phase of the cell cycle was observed 24 h post ozone. RNA-seq revealed significant enrichment of pathways involved in innate immune signaling and cytokine production among differentially expressed genes at both 24 and 72 h after ozone, whereas pathways involved in cell cycle regulation were upregulated at 24 h and intracellular metabolism at 72 h. An interaction network analysis identified tumor suppressor 53 (TP53), E2F family of transcription factors (E2Fs), cyclin-dependent kinase inhibitor 1A (CDKN1a/p21), and cyclin D1 (CCND1) as upstream regulators of cell cycle pathways at 24 h and TP53, nuclear receptor subfamily 4 group a member 1 (NR4A1/Nur77), and estrogen receptor alpha (ESR1/ERα) as central upstream regulators of mitochondrial respiration pathways at 72 h. To assess whether ERα regulates metabolic activity, we used ERα-/- mice. In both air and ozone-exposed mice, loss of ERα resulted in increases in glycolytic capacity and glycolytic reserve in lung macrophages with no effect on mitochondrial oxidative phosphorylation. Taken together, these results highlight the complex interaction between cell cycle, intracellular metabolism, and macrophage activation which may be important in the initiation and resolution of inflammation following ozone exposure.

Estimation of the bar stress based on crack width measurements in reinforced concrete structures

AbstractEstimating the stress of reinforcing bars and its variations in service conditions can be useful to determine the reserve capacity of structures or to assess the risk of fatigue in the reinforcement. This paper investigates the use crack width measurements to estimate the stress in the bars. In existing structures, crack width formulations can be used to estimate the stress in the reinforcement from crack width measurements, profiting from additional information that can be measured in‐situ, such as the crack spacing. Recent experimental results show that the values of the mean bond stress typically considered in code formulations overestimate the actual bond stresses activated in cracked concrete specimens. This paper presents the results of an experimental program consisting of reinforced concrete ties and beams instrumented with Digital Image Correlation and fiber optical measurements. The results confirm the differences with typically assumed bond stresses. A formulation to estimate the bond stresses in service conditions is derived from the results of the numerical integration of a previously developed local bond–slip relationship. Their pertinence for the estimation of the stress in the reinforcement from the measured crack width is evaluated with satisfactory results for monotonic loading and for the maximum force in cyclic tests.

Energy and reserve procurement in integrated electricity and heating system: A high-dimensional covariance matrix approach based on stochastic differential equations

The integration of stochastic renewable energy sources into energy systems presents challenges due to flexibility insufficiency and uncertainty modeling inaccuracy. To address these challenges, this paper explores a high-dimensional covariance matrix approach based on stochastic differential equations (SDEs) for energy and reserve co-dispatch in integrated electricity and heating systems. By capturing the long-term correlation of wind power forecast errors, the SDE model simultaneously models point forecasts and high-dimensional positive-definite covariance matrices, resulting in a compact uncertainty set. To ensure computational efficiency, we employ duality theory to transform the stochastic co-dispatch problem with the high-dimensional uncertainty set into deterministic convex programming. Additionally, a virtual heat storage model is introduced for the district heating network, leveraging the thermal inertia of the network to enhance reserve capacity. Simulations validate the calibration and sharpness of the proposed high-dimensional uncertainty set. The results demonstrate that co-dispatch using the SDE-based uncertainty set reduces operational costs by 4.9% compared to a set that does not consider the long-term correlation of wind power, under a 95% coverage rate. Moreover, the storage capabilities of district heating pipelines and smart buildings provide cost-free reserves, saving the operational costs of the two test systems by 2.8% and 1.3%, respectively.

Flexible resource demand response scheduling strategy under 5G-V2X

Electric vehicles (EV) and 5 G base stations, functioning as flexible load resources, contribute significantly to the provision of ample reserve capacity for the power grid. The emergence of 5 G Vehicle-to-Everything (V2X) technology has fostered a coupling between EV and base stations, further enhancing their roles within the power grid. Building upon this foundation, this paper proposes a scheduling strategy for demand response in flexibility resources under the 5 G-V2X framework. Initially, the dispatchable load of EV is examined in conjunction with the traffic network. Subsequently, we consider the communication power consumption resulting from the connected vehicle model, enabling us to devise path planning and charging navigation strategies for EV. Lastly, we establish a scheduling decision model that aims to minimize both the operation costs of base stations and the variance in grid load. The simulation is validated using real-world road conditions in the primary urban area of a city. The findings illustrate that the proposed dispatching strategy not only achieves a mutually beneficial outcome for EV users and aggregators, without disrupting EV charging and discharging processes, but also enhances the capability of demand response, thereby ensuring reliable grid operation.

Adaptive immune response in women from the Russian Arctic region after COVID-19 infection

BACKGROUND: The Arctic region of Russia is characterized by disproportionately high rates of morbidity and mortality from COVID-19 during the pandemic. The harsh climatic and environmental conditions in this area impede the development of self-regulation processes resulting in activation and strain of both cellular and humoral immunity. This leads to a depletion of the body’s reserve capacities. At present, there is lack of research examining how individuals who have recovered from COVID-19 are affected by the extreme conditions of Arctic Russia. AIM: To study the ratio of immunocompetent cells involved in the adaptive immune response following COVID-19 infection. MATERIAL AND METHODS: A total of 29 women aged 20 – 40 years were examined in Arkhangelsk as part of a comprehensive immunological study. This study involved assessment of the number of leukocytes, lymphocytes, and their phenotypes (CD5+, CD8+, CD10+, CD95+), as well as determination of phagocytic activity and phagocytic number. RESULTS: The cellular adaptive immune response in observed individuals 6 months after experiencing moderate COVID-19 disease was characterized by a very low concentration of T cells (CD5+) in all cases, CD10+ lymphocytes (44.83%) alongside with a high concentration of cytotoxic lymphocytes (CD8+) in 48.27% of individuals and lymphocytes with receptors for apoptosis (CD95+) in 51.72%, with relatively high phagocytic activity ranging from 90 to 100%. A correlation was found in 11.29% of women between the low content of CD10+ and CD95+ cells with the activity of phagocytosis. In 40% of women with high phagocytic activity, the concentrations of cytotoxic cells (CD8+) were found to be at a minimum level. CONCLUSIONS: Women with high phagocytic activity were found to have the lowest concentrations of cytotoxic cells, suggesting a potentially positive prognosis for reducing the risk of complications. This indicates that cellular immunity may play a role in determining the severity of COVID-19 infection in individuals with high phagocytic activity.

Planning of Production Capacities of Precast Construction Plants under Conditions of Changes in Demand for Products

The main criterion for a feasibility study of the production efficiency of precast construction plants, analysis of internal production reserves and optimal production volume is the production capacity indicator. Thus, the study of various Factors influencing the production capacity indicators is an important task. The results of research of the influence of the number of storeys and the set of block sections in the configuration of industrial residential buildings on changes in the ratio of product types in the range of the production programme of plants are presented in the paper. Fluctuations in the ratio of product types during the construction of different types of houses have been established. Based on the obtained results, the dependence of the production capacity plants on fluctuations in the ratio of product types has been constructed. It has been determined that the main reason for the revealed facts of a decrease in production capacity is the uneven loading of production lines with fluctuations in the ratio of product types in the range of production programs of precast construction plants. Taking into account the known facts of the dependence of production capacity on the concrete capacity of block sections of houses, the results of a comparison of the degree of influence of concrete capacity on the production capacity and the ratio of the main types of products in the range of production programs of plants are presented in the paper. It has been established that a key influence on the indicators of production capacity is exerted by changes in the ratio of product types. On the basis of the conducted research, optimal reserves of production capacity have been determined with a high share of different types of houses in the production programs of the plants. Taking into account the established indicators of production capacity reduction, their optimal reservation is within 20–25 % of the design capacity of the plants, which should serve as a reference point when planning the functioning of the production management system under the conditions of changes in demand for products.

An advanced farm flow estimator for the real-time evaluation of the potential wind power of a down-regulated wind farm

This work aims at verifying the predictions of OnWaRDS, an open-source wake modelling framework that captures the main features of the wake dynamics, including its meandering, in ancillary services scenarios. OnWaRDS brings together Lagrangian flow modeling and flow sensing and runs in parallel with a wind farm environment (here Large-Eddy simulations coupled to an Actuator Disk model (LES-AD)) in order to use the available rotor states to predict the flow field. The performances of OnWaRDS are first assessed when it runs synchronously with the LES-AD of a down-regulated wind farm and tends to mimic the LES-AD behavior. This synchronous mode implies a continuous feeding of the wake model with LES-AD rotor data. Then, OnWaRDS is used in a predictive mode, in order to predict an alternate reality for the wind farm. In this study, OnWaRDS aims at evaluating, in real-time, what the potential power production would be when the LES-AD is down-regulated to provide operating reserve capacity to the electricity network. Switching to a predictive mode implies that certain measurements at the wind turbine level can no longer be used, because the flow and the rotor behavior change between LES-AD and OnWaRDS. The second part of this study thus aims at verifying the predictions of OnWaRDS, and highlighting the impact of switching from a synchronous to a predictive mode in OnWaRDS.

Targeting exercise and sedentary behavior for the prevention of allogeneic stem cell transplant-related cardiovascular dysfunction: The ALLO-Active trial.

12018 Targeting Exercise and Sedentary Behavior to Prevent Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: The ALLO-Active Trial Background: Allogeneic stem cell transplantation (allo-SCT) is a potentially life-saving therapy for hematological malignancy, however, quality of life and longevity post allo-SCT are hampered by exercise intolerance, cardiac dysfunction, and cardiovascular mortality. This randomized controlled trial evaluated the efficacy of a novel multi-component activity program on cardiorespiratory fitness (peak oxygen uptake [VO2peak]) and cardiac function in adults undergoing allo-SCT. Methods: Sixty-two hematological malignancy patients scheduled for allo-SCT were randomized to a 4-month multi-component Activity program (n = 30) designed to increase aerobic and resistance exercise (3-day.week-1) and reduce sedentary time (≥30-min.day-1), or to usual care ( UC, n = 32). The Activity program was delivered over two distinct phases: ‘Inpatient’, which commenced upon admission for allo-SCT and continued until discharge (~4 weeks), and ‘Outpatient’,which commenced at discharge and continued for 12-weeks. Physiological assessments were conducted pre-admission, and 12-weeks post-discharge (4-months from baseline) and included: (1) cardiopulmonary exercise testing to quantify VO2peak, (2) exercise cardiac magnetic resonance imaging to determine peak cardiac output and stroke volume index (COIpeak and SVIpeak), (3) standard of care resting echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and (4) cardiac biochemistry (troponin, B-type natriuretic peptide). Results: Fifty-two patients (84%) completed follow-up (25 Activity; 27 UC), and median (IQR) intervention adherence was 73% (50-81). Activity preserved VO2peak (-0.9ml.kg-1.min-1 [95%CI -2.5, 0.8]) which showed a marked decline with UC (-3.4ml.kg-1.min-1 [95%CI -4.9, -1.8]; interaction, p= 0.029). Activity also showed significant benefits on exercise cardiac function, as shown by a preservation of COIpeak (0.30L.min-1.m2, [95%CI -0.34, 0.41]) and SVIpeak (0.6ml.m2 [95%CI -1.3, 2.5]), both of which declined with UC (COIpeak: -0.68L.min-1.m2, [95%CI -1.3, -0.32]; interaction, p= 0.008; SVIpeak: -2.7ml.m2 [95%CI -4.6, -0.9], interaction, p =0.014). There were no treatment effects of Activity on cardiac injury biomarkers or global longitudinal strain and no changes in left ventricular ejection fraction in either group. Conclusions: Intervening early in the allo-SCT process with an exercise and sedentary behavior intervention can have significant benefits for the preservation of patient’s cardiovascular reserve capacity. Our results may have important long-term implications for cardiovascular disease incidence and mortality in allo-SCT recipients. Clinical trial information: ANZCTR12619000741189.

Integrated production simulation of renewable energy and transportation consumption

Abstract In order to improve the reserve adequacy of high proportion new energy power systems and realize the efficient consumption of large-scale new energy, the source of reserve resources is expanded to the source network and load storage, and the operating reserve level that can be provided by the source network and load storage flexible regulating resources is quantified in terms of the direction of regulation and the mode of participation. Then, according to the regulation idea of “synchronous units bear the responsibility during regular hours and multiple types of resources share the responsibility during special hours”, a coordinated and participatory operating reserve capacity allocation strategy of source, network, load, and storage is proposed, and a reserve distribution optimization model incorporating multiple types of heterogeneous resources is constructed to achieve the optimization of reserve distribution of each type of reserve resource in the whole network. The optimization model of standby distribution is constructed to incorporate multiple types of heterogeneous resources and realize the step-by-step refinement of standby resources distribution among the whole grid - resources of the same type - units/stations. A case study is carried out based on a provincial power grid, and the effectiveness of the proposed strategy is verified by comparing it with the existing operational reserve allocation guidelines.

Algorithms for online fault tolerance server consolidation

We study a novel replication mechanism to ensure service continuity against multiple simultaneous server failures. In this mechanism, each item represents a computing task and is replicated into ξ+1 servers for some integer ξ≥1, with workloads specified by the amount of required resources. If one or more servers fail, the affected workloads can be redirected to other servers that host replicas associated with the same item, such that the service is not interrupted by the failure of up to ξ servers. This requires that any feasible assignment algorithm must reserve some capacity in each server to accommodate the workload redirected from potential failed servers without overloading, and determining the optimal method for reserving capacity becomes a key issue. Unlike existing algorithms that assume that no two servers share replicas of more than one item, we first formulate capacity reservation for a general arbitrary scenario. Due to the combinatorial nature of this problem, finding the optimal solution is difficult. To this end, we propose a Generalized and Simple Calculating Reserved Capacity (GSCRC) algorithm, with a time complexity only related to the number of items packed in the server. In conjunction with GSCRC, we propose a robust replica packing algorithm with capacity optimization (RobustPack), which aims to minimize the number of servers hosting replicas and tolerate multiple server failures. Through theoretical analysis and experimental evaluations, we show that the RobustPack algorithm can achieve better performance.