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Adequate real-world safety and efficacy of leadless pacemakers (LPs) have been demonstrated up to 3 years after implantation. Longer-term data are warranted to assess the net clinical benefit of leadless pacing. The purpose of this study was to evaluate the long-term safety and efficacy of LP therapy in a real-world cohort. In this retrospective cohort study, all consecutive patients with a first LP implantation from December 21, 2012, to December 13, 2016, in 6 Dutch high-volume centers were included. The primary safety endpoint was the rate of major procedure- or device-related complications (ie, requiring surgery) at 5-year follow-up. Analyses were performed with and without Nanostim battery advisory-related complications. The primary efficacy endpoint was the percentage of patients with a pacing capture threshold ≤2.0 V at implantation and without ≥1.5-V increase at the last follow-up visit. A total of 179 patients were included (mean age 79 ± 9 years), 93 (52%) with a Nanostim and 86 (48%) with a Micra VR LP. Mean follow-up duration was 44 ± 26 months. Forty-one major complications occurred, of which 7 were not advisory related. The 5-year major complication rate was 4% without advisory-related complications and 27% including advisory-related complications. No advisory-related major complications occurred a median 10 days (range 0–88 days) postimplantation. The pacing capture threshold was low in 163 of 167 patients (98%) and stable in 157 of 160 (98%). The long-term major complication rate without advisory-related complications was low with LPs. No complications occurred after the acute phase and no infections occurred, which may be a specific benefit of LPs. The performance was adequate with a stable pacing capture threshold. [ABSTRACT FROM AUTHOR]

Sustainable microgrid is a feasible approach to handle environmental impacts and satisfy customer demand due to its economic, environmental, and social benefits. Due to the high initial investment cost, the installation rate of microgrids has been limited. Various studies investigated the influence of government subsidies on sustainable microgrid design to increase the installation rate. However, the effect of government subsidies, financial factors, and elasticity coefficient of demand under peer-to-peer energy trading has not been explored in the current sustainable microgrids design literature. To overcome this limitation, this paper investigates the sustainable microgrid design problem to simultaneously consider the effect of government subsidies, peer-to-peer energy trading, time value of money, elasticity coefficient of demand, and uncertainties. The objectives are to maximize total profit and minimize the total environmental cost to satisfy electric energy demand. Fuzzy multi-objective programming is applied to determine the optimal decisions on the number, location, type of renewable energy, the capacity of renewable distributed generation sources, electricity flows, price for selling electricity to demand areas and P2P energy trading, and government subsidy rates. A genetic algorithm and its hybrid versions to include tabu search and simulated annealing are then used to solve the proposed model. Numerical experiments used to evaluate the performance of the proposed model and algorithms show that the proposed genetic algorithm is most effective in maximizing total profit and minimizing environmental cost. Computational results demonstrate that on average, the inclusion of the peer-to-peer trading and government subsidies in the proposed model increases total profit by 13.23% and reduces total environmental cost by 6.29%. [Display omitted] • Sustainable microgrid design problem under impacted factors is investigated. • The effect of government subsidies and peer-to-peer energy trading are assessed. • Economic, environmental, and social objectives are considered under impacted factors. • Fuzzy multi-objective programming model is developed to handle the uncertainty. • Genetic algorithm and its hybrid versions are used to solve the propose model. [ABSTRACT FROM AUTHOR]

Objective: During multi-domain operations (MDO), soldiers need the physical supremacy, cognitive dominance, and emotional resilience to help defend and win our nation's wars. Optimal sleep has been shown to boost physical performance and cognitive processing. This manuscript will discuss how recent advances in sleep science strongly argue for the integration of sleep planning into military operations.Design: Review article.Methods: We reviewed the current understanding of how sleep affects Soldier readiness, how sleep and pain are interrelated, and unique challenges to obtaining adequate sleep in military training environments. We then address solutions that can be implemented by leaders and individuals to manage warfighter fatigue and optimize unit performance.Results: Since sleep is foundational to soldier health and readiness, improving warfighter fatigue management is a priority for leaders.Conclusion: To succeed in MDO, military personnel require physical supremacy, cognitive dominance, and emotional resilience to fight and win. Sleep science is a rapidly emerging field, and the clear implications for maximizing human performance argue strongly for more deliberate integration into military training and operations. Leaders that incorporate sleep and fatigue management into the planning and execution phases of operations will help facilitate mission priorities and prove a powerful force multiplier. [ABSTRACT FROM AUTHOR]

Perchlorate (ClO 4 −) salts were discovered on Mars and are known to absorb water vapor from the atmosphere and deliquesce into the aqueous phase. Other species such as chlorides (Cl−) and chlorates (ClO 3 −) were also identified; these species can affect the deliquescence of perchlorates. Here we generate phase diagrams of perchlorate/chloride and perchlorate/chlorate binary mixtures for K, Na, Mg and Ca in the temperature range 223–273 K. Using a new approach based on thermodynamic modelling of evaporation, we determined the deliquescence relative humidity (the minimum relative humidity at which a salt converts into a liquid by absorbing atmospheric water vapor) and the eutonic relative humidity (the minimum relative humidity at which two salts are in equilibrium with liquid) for binary salt mixtures. Our modelling results show that the deliquescence relative humidity values of all salt mixtures is always lower than that of each individual end-member salt at a fixed temperature, typically a few percent lower. The closer the eutonic is to one of the end-member, the smaller the decrease in relative humidity compared to the pure pole. Thus, only eutonics which are far from both poles exhibit a significant drop in relative humidity. Moreover, the eutonic relative humidity always increases with decreasing temperature, which does not favor liquids in the dry and cold Martian environment. Finally, the increased stability of water ice at the lowest temperatures always reduces or even eliminates the stability of liquids. Therefore, the favorable temperature and relative humidity conditions under which binary salt liquid mixtures exist are generally not significantly improved compared to single salts. [ABSTRACT FROM AUTHOR]

Background: Risk stratification for sudden cardiac death (SCD) in cardiac sarcoidosis (CS) is challenging in patients without overt cardiac symptoms.Objective: The purpose of this study was to determine the incidence of ventricular arrhythmias (VAs) and mortality after long-term monitoring with a cardiovascular implantable electronic device (CIED) in CS patients identified after systematic screening of patients with extracardiac sarcoidosis (ECS).Methods: A retrospective study was performed in 547 predominantly Caucasian patients with ECS screened for cardiac involvement. If CS was diagnosed, risk stratification (high vs low risk) for SCD was performed by a multidisciplinary team. The primary endpoint was defined as sustained VA, appropriate implantable cardioverter-defibrillator (ICD) therapy, or cardiac death.Results: In total, 105 patients were included (mean follow-up 33 ± 16 months). An ICD was implanted in 17 high-risk patients (16.2%), whereas 80 low-risk patients (76.1%) received an implantable loop recorder (ILR). Eight low-risk patients (7.6%) did not receive a device. The primary endpoint occurred in 4.8% (n = 5), with an overall annualized event rate of 1.7%. The annualized event rate was 9.8% in high-risk patients and 0.4% in low-risk patients. Nine low-risk patients received an ICD during follow-up, in 7 patients as a result of the ILR recordings. None of these patients required ICD therapy.Conclusion: In CS patients without overt cardiac symptoms at initial presentation the annualized overall event rate was 1.7%; 10% in high-risk patients, but only 0.4% in low-risk patients. In low-risk patients long-term arrhythmia monitoring with an ILR enabled early detection of clinically important arrhythmias without showing impact on prognosis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is conceptualized as a synaptic failure disorder in which loss of glutamatergic synapses is a major driver of cognitive decline. Thus, novel therapeutic strategies aimed at regenerating synapses may represent a promising approach to mitigate cognitive deficits in AD patients. At present, no disease-modifying drugs exist for AD, and approved therapies are palliative at best, lacking in the ability to reverse the synaptic failure. Here, we tested the efficacy of a novel synaptogenic small molecule, SPG302 — a 3rd-generation benzothiazole derivative that increases the density of axospinous glutamatergic synapses — in 3xTg-AD mice. Daily dosing of 3xTg-AD mice with SPG302 at 3 and 30 mg/kg (i.p.) for 4 weeks restored hippocampal synaptic density and improved cognitive function in hippocampal-dependent tasks. Mushroom and stubby spine profiles were increased by SPG302, and associated with enhanced expression of key postsynaptic proteins — including postsynaptic density protein 95 (PSD95), drebrin, and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) — and increased colocalization of PSD95 with synaptophysin. Notably, SPG302 proved efficacious in this model without modifying Aβ and tau pathology. Thus, our study provides preclinical support for the idea that compounds capable of restoring synaptic density offer a viable strategy to reverse cognitive decline in AD. [ABSTRACT FROM AUTHOR]

Objectives: Explore the impact transitioning from daytime to nighttime operations has on performance in U.S. Army Rangers.Methods: Fifty-four male Rangers (age 26.1±4.0 years) completed the Y-Balance Test (YBT), a vertical jump assessment, and a grip strength test at three time points. Baseline testing occurred while the Rangers were on daytime operations; post-test occurred after the first night into the nighttime operation training (after full night of sleep loss), and follow-up testing occurred six days later (end of nighttime training).Results: On the YBT, performance was significantly worse at post-test compared to baseline during right posteromedial reach (104.1±7.2cm vs 106.5±6.7cm, p=.014), left posteromedial reach (105.4±7.5cm vs 108.5±6.6cm, p=.003), right composite score (274.8±19.3cm vs 279.7±18.1cm, p=.043), left composite score (277.9±18.1cm vs 283.3±16.7cm, p=.016), and leg asymmetry was significantly worse in the posterolateral direction (4.8±4.0cm vs 3.7±3.1cm, p=.030) and the anterior direction (5.0±4.0cm vs 3.6±2.6cm, p=.040). The average vertical jump height was significantly lower at post-test compared to baseline (20.6±3.4 in vs 21.8±3.0 in, p=.004). Baseline performance on YBT and vertical jump did not differ from follow-up.Conclusions: Army Rangers experienced an immediate, but temporary, drop in dynamic balance and vertical jump performance when transitioning from daytime to nighttime operations. When feasible, Rangers should consider adjusting their sleep cycles prior to anticipating nighttime operations in order to maintain their performance levels. Investigating strategies that may limit impairments during this transition is warranted. [ABSTRACT FROM AUTHOR]

In recent decades, global climate change has become one of the most critical environmental issues, leading to increased environmental and social concerns about the sustainability of logistics networks. This study proposes a novel multi-objective, multi-facility location–allocation model for a two-stage solid logistics network that supports green practices. To account for uncertainty in real-world problems, some parameters of the model are represented as triangular type-2 neutrosophic numbers to deal with hesitant situations. The fuzzy model is then converted into a deterministic one using a new ranking approach. Three conflicting objective functions – minimizing total financial costs, maximizing customers' satisfaction levels, and ensuring sustainable and effective conveyances – are simultaneously optimized using the ϵ -constraint approach. The proposed model and solution approach are tested with two numerical examples. A comparative study is also presented, comparing the proposed approach with other Pareto-based multi-objective approaches, such as the global criterion approach, multi-objective fuzzy programming, and weighted Chebychev programming. Finally, the paper concludes with some remarks. • A model integrating location–allocation, two-stage, and solid logistics problems. • Analyzed mixed-integer non-linear multi-objective model under two-fold uncertainty. • De-neutrosophic based on a novel ranking function for sustainable decision-making. • Conducted a comparative analysis of the proposed model against existing approaches. • Demonstrated the impact of carbon emissions constraint with two applications. [ABSTRACT FROM AUTHOR]

This research investigates the Set Team Orienteering Problem with Time Windows (STOPTW), a new variant of the well-known Team Orienteering Problem with Time Windows and Set Orienteering Problem. In the STOPTW, customers are grouped into clusters. Each cluster is associated with a profit attainable when a customer in the cluster is visited within the customer's time window. A Mixed Integer Linear Programming model is formulated for STOPTW to maximizing total profit while adhering to time window constraints. Since STOPTW is an NP-hard problem, a Simulated Annealing with Reinforcement Learning (SA RL) algorithm is developed. The proposed SA RL incorporates the core concepts of reinforcement learning, utilizing the ε-greedy algorithm to learn the fitness values resulting from neighborhood moves. Numerical experiments are conducted to assess the performance of SA RL , comparing the results with those obtained by CPLEX and Simulated Annealing (SA). For small instances, both SA RL and SA algorithms outperform CPLEX by obtaining eight optimal solutions and 12 better solutions. For large instances, both algorithms obtain better solutions to 28 out of 29 instances within shorter computational times compared to CPLEX. Overall, SA RL outperforms SA by resulting in lower gap percentages within the same computational times. Specifically, SA RL outperforms SA in solving 13 large STOPTW benchmark instances. Finally, a sensitivity analysis is conducted to derive managerial insights. [ABSTRACT FROM AUTHOR]

With a greater awareness of the challenges regarding environmental, societal, political, and economic factors, where reverse logistics has become a significant part of supply chain networks, this paper presents an integrated forward and reverse logistics network, named the Heterogeneous Fleet Vehicle Routing Problem with Multiple Forward/Reverse Cross-Docks (HF-VRPMFRCD). We consider a heterogeneous fleet of vehicles with different loading capacities and transportation costs. We also consider multiple cross-docks with two different operations: forward and reverse processes. The former focuses on delivering the demand from suppliers to customers, while the latter aims at returning unsold products from customers to suppliers. We propose a Simulated Annealing with Variable Neighborhood Descent (SAVND) algorithm for solving HF-VRPMFRCD, where Variable Neighborhood Descent (VND) is a local search heuristic embedded in the framework of Simulated Annealing (SA). SAVND outperforms the state-of-the-art algorithm in solving the Heterogeneous Fleet Vehicle Routing Problem with Multiple Cross-Docks (HF-VRPMCD), where the VND heuristic significantly improves the quality of solutions. For HF-VRPMFRCD benchmark instances, SAVND provides optimal solutions for small-scale instances and better solutions than those of the GUROBI solver for remaining larger instances. Lastly, we present and discuss the benefits of integrating the forward and reverse processes. • We study the heterogeneous fleet VRP with multiple forward/reverse cross-docks. • We formulate a mixed-integer linear programming model for the problem. • We develop a simulated annealing with variable neighborhood descent approach. • We present sensitivity analyses and managerial insights. [ABSTRACT FROM AUTHOR]