Population Protocols Research Articles

Evaluating anticoagulation sensitivity among elderly patients managed with an institution's heparin protocol using initial anti-factor Xa levels.

The purpose of this study was to assess an institution's heparin protocols in elderly and nonelderly adult populations to see if a response difference was observed. This was a retrospective cohort study of hospitalized adults who were prescribed unfractionated heparin due to surgery, acute coronary syndrome (ACS), or deep vein thrombosis/pulmonary embolism (DVT/PE) from February 11, 2016, through August 1, 2017. Patients were divided into nonelderly adults 18 to 69 years of age and elderly patients 70 years of age or older. The anti-factor Xa (anti-Xa) level after protocol initiation was compared to the institution's goal range of 0.3 to 0.7 IU/mL. Outcomes of each protocol in the elderly population were compared to outcomes in their nonelderly counterparts to determine if there was a difference in heparin response. A total of 325 patients were included in the analysis, comprising 150 elderly and 175 nonelderly adults. Elderly patients had a higher initial anti-Xa levels than did their nonelderly adult counterparts in the ACS, DVT/PE, and surgery protocols, with P values of 0.02, <0.001, and 0.01, respectively. Only the ACS protocol demonstrated increased frequency of above-target-level anti-Xa levels in the elderly (P = 0.03). Elderly patients had significantly higher initial anti-Xa levels than did nonelderly adult patients across all protocols. This study identifies the need to further study elderly patients' increased heparin sensitivity to determine if a separate dosing protocol is needed.

Introduction to the Special Section on Network Science in Biological and Bio-Inspired Systems

The papers in this special section examine network science in biological and bio-inspired systems. Networks exist widely in biological systems, including neuronal networks, protein-protein interaction networks, metabolic networks, gene regulatory networks, food web, microbiome, and local interactions in flocks. These biological systems have inspired several intelligent algorithms such as genetic algorithms, artificial neural networks, particle swarm optimization, population protocol, to name a few. As biological and bio-inspired systems are distributed and usually operate without central control, network science is an elegant and powerful framework to investigate their structure and functions. Indeed, network biology and networked bio-inspired systems have recently attracted significant attentions and become a promising interdisciplinary field. The papers in this section focus on the structure and functions of biological and bio-inspired networks.

In vitro corrosion studies of stainless-steel dental substrates during Porphyromonas gingivalis biofilm growth in artificial saliva solutions: providing insights into the role of resident oral bacterium.

Stainless-steel AISI 321 is an effective material for fabricating dental crowns and other implants utilized dental restorative protocols for elderly and pediatric populations. This unique clinical application is possible through the mechanical stability and corrosion-resistance properties of this metallic material. However, stainless-steel dental implants eventually fail, leading to the creation of surface cavities and cracks within their microstructures during persistent mechanical stresses and biocorrosion. In this study, the in vitro corrosion behaviour of a medical-grade stainless-steel dental substrate was investigated during Porphyromonas gingivalis biofilm growth process in artificial saliva culture suspension (ASCS). Among the causative bioagents of corrosion, P. gingivalis was chosen for this study since it is also responsible for oral periodontitis and a major contributing factor to corrosion in most dental implants. Increased P. gingivalis growth was observed within the incubation period under study as compact cellular clusters fouled the metal surfaces in ASCS media. This led to the corrosion of steel substrates after bacterial growth maturity within 90 days. Corrosion rate increased with higher CFU and bacterial incubation period for all test substrates due to biocorrosion incited by the volatile sulphide products of P. gingivalis metabolism. The presence of some of these volatile compounds has been observed from experimental evidences. Significant anodic degradation in the forms of localized pitting were also recorded by surface analytical techniques. Residual fluorinated ions within the ASCS media also increased the rate of anodic dissolution due to media acidity. This study has provided extensive insights into the fate of stainless-steel dental crown in oral environments infected by a resident oral bacterium. Influences of oral conditions similar to fluoride-enriched mouthwashes were reflected in a view to understanding the corrosion patterns of stainless-steel dental substrates.

Comparative cytogenetic survey of the giant bonytongue Arapaima fish (Osteoglossiformes: Arapaimidae), across different Amazonian and Tocantins/Araguaia River basins

Abstract The South American giant fishes of the genus Arapaima, commonly known as pirarucu, are one of the most iconic among Osteoglossiformes. Previously cytogenetic studies have identified their karyotype characteristics; however, characterization of cytotaxonomic differentiation across their distribution range remains unknown. In this study, we compared chromosomal characteristics using conventional and molecular cytogenetic protocols in pirarucu populations from the Amazon and Tocantins-Araguaia river basins to verify if there is differentiation among representatives of this genus. Our data revealed that individuals from all populations present the same diploid chromosome number 2n=56 and karyotype composed of 14 pairs of meta- to submetacentric and 14 pairs of subtelo- to acrocentric chromosomes. The minor and major rDNA sites are in separate chromosomal pairs, in which major rDNA sites corresponds to large heterochromatic blocks. Comparative genomic hybridizations (CGH) showed that the genome of these populations shared a great portion of repetitive elements, due to a lack of substantial specific signals. Our comparative cytogenetic data analysis of pirarucu suggested that, although significant genetic differences occur among populations, their general karyotype patterns remain conserved.

Loosely-stabilizing leader election with polylogarithmic convergence time

A loosely-stabilizing leader election protocol with polylogarithmic convergence time in the population protocol model is presented in this paper. In the population protocol model, which is a common abstract model of mobile sensor networks, it is known to be impossible to design a self-stabilizing leader election protocol unless the exact number of agents is known a priori. Thus, in our prior work, we introduced concept of loose-stabilization, which is weaker than self-stabilization but has similar advantage in practice. Following this work, several loosely-stabilizing leader election protocols have been given. Loosely-stabilizing leader election guarantees that, starting from an arbitrary configuration, the system reaches a safe configuration with a single leader within a short time, and keeps the unique leader for a long time thereafter. The convergence times of all existing loosely-stabilizing protocols, i.e., the expected times to reach a safe configuration, are polynomial in n where n is the number of nodes, while their holding times, i.e., the expected times to keep the unique leader after reaching a safe configuration, are exponential in n. In this paper, a loosely-stabilizing protocol with polylogarithmic convergence time is presented. Its holding time is not exponential, rather an arbitrarily large polynomial function of n.

Data collection in population protocols with non-uniformly random scheduler

Contrary to many previous studies on population protocols using the uniformly random scheduler, we consider a more general non-uniform case. Here, pair-wise interactions between agents (moving and communicating devices) are assumed to be drawn non-uniformly at random. While such a scheduler is known to be relevant for modeling many practical networks, it is also known to make the formal analysis more difficult.This study concerns data collection, a fundamental problem in mobile sensor networks (one of the target networks of population protocols). In this problem, pieces of information given to the agents (e.g., sensor readings) should be eventually delivered to a predefined sink node without loss or duplication. Following an idea of the known deterministic protocol TTF solving this problem, we propose an adapted version of it and perform a complete formal analysis of execution times in expectation and with high probability (w.h.p.).We further investigate the important issue of energy consumption. The goal is to improve TTF in terms of energy complexity, while still keeping good time complexities (in expectation and w.h.p.). Namely, we propose a new parameterized protocol for data collection, called lazy TTF, and present a study showing that an appropriate choice of the protocol parameters can considerably improve energy performances (compared to TTF), at a slight expense of time performance.

Immediate Observation in Mediated Population Protocols

In this paper we analyze the computational power of variants of population protocols (PP), a formalism for distributed systems with anonymous agents having very limited capabilities. The capabilities of agents are enhanced in mediated population protocols (MPP) by recording the states in the edges of the interaction graph. Restricting the interactions to the communication model of immediate observation (IO) reduces the computational power of the resulting formalism. We show that this enhancement and restriction, when combined, yield a model (IOMPP) at least as powerful as the basic PP. The proof requires a novel notion of configurations in the MPP model allowing differentiation of agents and uses techniques similar to methods of analyzing encoding criteria, namely operational correspondence. The constructional part of the proof is generic in a way that all protocols can be translated into the new model without losing the desirable properties they might have besides a stable output. Furthermore, we illustrate how this approach could be utilized to prove our conjecture of IOMPP model being even as expressive as the MPP model. If our conjecture holds, this would result in a sharp characterization of the computational power and reveal the nonnecessity of two-way communication in the context of mediated population protocols.

Approximate majority analyses using tri-molecular chemical reaction networks

Approximate Majority is a well-studied problem in the context of chemical reaction networks (CRNs) and their close relatives, population protocols: Given a mixture of two types of species with an initial gap between their counts, a CRN computation must reach consensus on the majority species. Angluin, Aspnes, and Eisenstat proposed a simple population protocol for Approximate Majority and proved correctness and $$O(\log n)$$ time efficiency with high probability, given an initial gap of size $$\omega (\sqrt{n}\log n)$$ when the total molecular count in the mixture is n. Motivated by their intriguing but complex proof, we provide a new analysis of several CRNs for Approximate Majority, starting with a very simple tri-molecular protocol with just two reactions and two species. We obtain simple analyses of three bi-molecular protocols, including that of Angluin et al., by showing how they emulate the tri-molecular protocol. Our results improve on those of Angluin et al. in that they hold even with an initial gap of $$\varOmega (\sqrt{n \log n})$$ . We prove that our tri-molecular CRN is robust even when there is some uncertainty in the reaction rates, when some molecules are Byzantine (i.e., adversarial), or when activation of molecules is triggered by epidemic. We also analyse a natural variant of our tri-molecular protocol for the more general problem of multi-valued consensus. Our analysis approach, which leverages the simplicity of a tri-molecular CRN to ultimately reason about these many variants, may be useful in analysing other CRNs too.

Central Limit Model Checking

We consider probabilistic model checking for continuous-time Markov chains (CTMCs) induced from Stochastic Reaction Networks against a fragment of Continuous Stochastic Logic (CSL) extended with reward operators. Classical numerical algorithms for CSL model checking based on uniformisation are limited to finite CTMCs and suffer from exponential growth of the state space with respect to the number of species. However, approximate techniques such as mean-field approximations and simulations combined with statistical inference are more scalable but can be time-consuming and do not support the full expressiveness of CSL. In this article, we employ a continuous-space approximation of the CTMC in terms of a Gaussian process based on the Central Limit Approximation, also known as the Linear Noise Approximation, whose solution requires solving a number of differential equations that is quadratic in the number of species and independent of the population size. We then develop efficient and scalable approximate model checking algorithms on the resulting Gaussian process, where we restrict the target regions for probabilistic reachability to convex polytopes. This allows us to derive an abstraction in terms of a time-inhomogeneous discrete-time Markov chain (DTMC), whose dimension is independent of the number of species, on which model checking is performed. Using results from probability theory, we prove the convergence in distribution of our algorithms to the corresponding measures on the original CTMC. We implement the techniques and, on a set of examples, demonstrate that they allow us to overcome the state space explosion problem, while still correctly characterizing the stochastic behaviour of the system. Our methods can be used for formal analysis of a wide range of distributed stochastic systems, including biochemical systems, sensor networks, and population protocols.

Systematic review of basic oral care for the management of oral mucositis in cancer patients and clinical practice guidelines.

The aim of this study was to update the clinical practice guidelines for the use of basic oral care (BOC) interventions for the prevention and/or treatment of oral mucositis (OM). A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention in each cancer treatment setting was assigned an evidence level. The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible. A total of 17 new papers across six interventions were examined and merged with a previous database. Based on the literature, the following guidelines were possible. The panel suggests that the implementation of multi-agent combination oral care protocols is beneficial for the prevention of OM during chemotherapy, head and neck (H&N) radiation therapy (RT), and hematopoietic stem cell transplantation (Level of Evidence III). The panel suggests that chlorhexidine not be used to prevent OM in patients undergoing H&N RT (Level of Evidence III). No guideline was possible for professional oral care, patient education, saline, and sodium bicarbonate, and expert opinion complemented these guidelines. The evidence supports the use of multi-agent combination oral care protocols in the specific populations listed above. Additional well-designed research is needed on the other BOC interventions prior to guideline formulation.

Improved Outcome of a Pediatric-Inspired Protocol for High-Risk Adolescent and Young Adult Acute Lymphoblastic Leukemia Patients Using Peg-Asparaginase and Escalating Dose of Methotrexate: Tolerability and Outcome

BackgroundTreatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients using traditional adult chemotherapy protocols give low overall survival (OS) rates. Data are growing regarding the use of pediatric-inspired chemotherapy protocols in AYA patients with improvement in OS. Patients and MethodsTo assess efficacy and tolerability of using a pediatric-inspired protocol in AYA patients, we initiated our local prospective trial using a modified version of the Children’s Cancer Group 1900 protocol for newly diagnosed high-risk Philadelphia chromosome-negative ALL patients. ResultsA total of 40 patients were enrolled in the study (from 2015 to 2018). The median age was 18 years (range, 14-34 years). The complete remission rate after induction was 37 patients [93%] and after a median follow-up of 5 years, OS, disease-free survival (DFS), and event-free survival were 75%, 72%, and 60%, respectively. Use of this protocol was well tolerated with manageable toxicities. Pegylated asparaginase was given to all patients during the induction phase and was well tolerated. ConclusionThe use of a pediatric-inspired protocol for high-risk AYA ALL patients was effective and well tolerated with improvement in OS and DFS compared with historical data using adult protocols in such populations.

Polymorphisms of ADME-related genes and their implications for drug safety and efficacy in Amazonian Amerindians

The variation in the allelic frequencies of polymorphic pharmacogenes among different ethnic groups may be responsible for severe adverse reactions to or altered efficacy of a wide variety of drugs. Amazonian Amerindian populations have a unique genetic profile that may have a fundamental on the efficacy and safety of certain drugs. The genetic characteristics of these populations are poorly known, which can negatively impact the systematic application of treatments guided by pharmacogenomic guidelines. We investigated the diversity of 32 polymorphisms in genes responsible for drug Absorption, Distribution, Metabolism and Excretion (ADME) in Amazonian Amerindians, and compared the findings with populations from other continents available in the 1000 Genomes database. We found significantly different (P ≤ 1.56E-03) allelic frequencies and genotype distributions in many study markers in comparison with African, European, American and Asian populations. Based on FST values, the Amerindian population was also the most distinct (mean FST = 0.09917). These data highlight the unique genetic profile of the indigenous population from the Brazilian Amazon region, which is potentially important from a pharmacogenetic viewpoint. Understanding the diversity of ADME- related genetic markers is crucial to the implementation of individualized pharmacogenomic treatment protocols in Amerindian populations, as well as populations with a high degree of admixture with this ethnic group, such as the general Brazilian population.

O uso dos exergames nos protocolos de reabilitação em diversas populações clínicas

The use of exergames in rehabilitation protocols in different clinical populations

The Dose Response for Sprint Interval Training Interventions May Affect the Time Course of Aerobic Training Adaptations.

Low vs. high volume sprint-interval training (SIT) sessions have shown similar physiological benefits after 8 weeks. However, the dose response and residual effects of shorter SIT bouts (<10 s) are unknown. Following a 6-wk control period, 13 healthy inactive males were assigned to a low dose (LDG: n = 7) or high dose (HDG: n = 6) supervised 6-wk intervention: ×2/wk of SIT (LDG = 2 sets of 5 × 6 s ON: 18 s OFF bouts; HDG = 4–6 sets); ×1/wk resistance training (3 exercises at 3 × 10 reps). Outcome measures were tested pre and post control (baseline (BL) 1 and 2), 72 h post (0POST), and 3-wk post (3POST) intervention. At 0POST, peak oxygen uptake (VO2peak) increased in the LDG (+16%) and HDG (+11%) vs. BL 2, with no differences between groups (p = 0.381). At 3POST, VO2peak was different between LDG (−11%) and HDG (+3%) vs. 0POST. Positive responses for the intervention’s perceived enjoyment (PE) and rate of perceived exertion (RPE) were found for both groups. Blood pressure, blood lipids, or body composition were not different between groups at any time point. Conclusion: LDG and HDG significantly improved VO2peak at 0POST. However, findings at 3POST suggest compromised VO2peak at 0POST in the HDG due to the delayed time course of adaptations. These findings should be considered when implementing high-dose SIT protocols for non-athletic populations.

Detection of chikungunya virus‐specific IgM on laser‐cut paper‐based device using pseudo‐particles as capture antigen

The incidence of arbovirus infections has increased dramatically in recent decades, affecting hundreds of millions of people each year. The Togaviridae family includes the chikungunya virus (CHIKV), which is typically transmitted by Aedes mosquitoes and causes a wide range of symptoms from flu-like fever to severe arthralgia. Although conventional diagnostic tests can provide early diagnosis of CHIKV infections, access to these tests is often limited in developing countries. Consequently, there is an urgent need to develop efficient, affordable, simple, rapid, and robust diagnostic tools that can be used in point-of-care settings. Early diagnosis is crucial to improve patient management and to reduce the risk of complications. A glass-fiber laser-cut microfluidic device (paper-based analytical device [PAD]) was designed and evaluated in a proof of principle context, for the analysis of 30 µL of patient serum. Biological raw materials used for the functionalization of the PAD were first screened by MAC-ELISA (IgM capture enzyme-linked immunosorbent assay) for CHIKV Immunoglobulin M (IgM) capture and then evaluated on the PAD using various human samples. Compared with viral lysate traditionally used for chikungunya (CHIK) serology, CHIKV pseudo-particles (PPs) have proven to be powerful antigens for specific IgM capture. The PAD was able to detect CHIKV IgM in human sera in less than 10 minutes. Results obtained in patient sera showed a sensitivity of 70.6% and a specificity of around 98%. The PAD showed few cross-reactions with other tropical viral diseases. The PAD could help health workers in the early diagnosis of tropical diseases such as CHIK, which require specific management protocols in at-risk populations.

A Population Protocol for Uniform k-partition under Global Fairness

In this paper, we consider a uniform k-partition problem in a population protocol model. The uniform k-partition problem divides a population into k groups of the same size. For this problem, we give a symmetric protocol with designated initial states under global fairness. The proposed protocol requires 3k-2 states for each agent. Since any protocol for the uniform k-partition problem requires ?(k) states to indicate a group, the space complexity of the proposed protocol is asymptotically optimal.

Energy Balancing by Wireless Energy Transfer in Sensor Networks

Wireless energy transfer is a technology to transmit electricity without wire, and it is a promising technology for charging battery of mobile devices. In battery powered sensor networks, it is important to balance electric energy of batteries of nodes in order to maximize the life time of networks. In this paper, we propose three distributed protocols to balance electric energy of batteries of nodes. The proposed algorithms are based on the population protocol model which is a computational model for networked nodes with very limited resources. The goals of the algorithms are twofold: minimizing the loss of electric energy caused by wireless transmission, and minimizing the time to balance. The proposed algorithms are evaluated by computer simulation.

Loosely-Stabilizing Leader Election for Arbitrary Graphs in Population Protocol Model

In the population protocol model [Angluin et al. 2006], it is impossible to design a self-stabilizing leader election protocol without any knowledge of the exact number of nodes in the system. The notion of loose-stabilization, which relaxes the closure requirement of self -stabilization, was introduced in 2009 to circumvent this impossibility. The notion can be described as follows: a loosely-stabilizing protocol guarantees that, starting from any initial configuration, a system reaches a safe configuration eventually, and after that, the system maintains its specification (e.g., the unique leader) not forever, but for a sufficiently long time. The previous work of the authors presented a loosely-stabilizing protocol that solves the leader election on complete graphs using only a given upper bound $N$N on the number of nodes $n$n in the system, instead of the exact value of $n$n. In this paper, we propose two loosely-stabilizing protocols that solve leader election for arbitrary graphs. One is a deterministic protocol that uses the unique identifiers of nodes while the other is a probabilistic protocol that works on anonymous networks. Given an upper bound $N$N on the number of nodes, both protocols maintain a unique leader for $\Omega (Ne^{2N})$Ω(Ne2N) expected steps (holding time) after entering a safe configuration. The first algorithm enters a safe configuration within $O(mN \, \log n)$O(mNlogn) expected steps (convergence time) while the second one does this within $O(mN^2\,\log N)$O(mN2logN) expected steps, where $m$m is the number of edges in the graph. Both protocols require only $O(\log N)$O(logN) bits for each node's memory. A novel concept, called the same speed timer is introduced, by which all nodes of the system can count down their timers at the same speed. This concept allows to achieve fast convergence time of both algorithms. To design the second protocol, we design a self-stabilizing two-hop coloring protocol, which is interesting in its own right. This protocol uses only $O(\log N)$O(logN) memory space per node. We establish a lower bound. Any loosely-stabilizing leader election protocol with expected exponential holding time requires $\Omega (mN)$Ω(mN) expected convergence time. This lower bound shows a near-optimality of the first algorithm.

Recent Algorithmic Advances in Population Protocols

Population protocols are a popular model of distributed computing, introduced by Angluin, Aspnes, Diamadi, Fischer, and Peralta [6] a little over a decade ago. In the meantime, the model has proved a useful abstraction for modeling various settings, from wireless sensor networks [35, 26], to gene regulatory networks [17], and chemical reaction networks [21]. In a nutshell, a population protocol consists of n agents with limited local state that interact randomly in pairs, according to an underlying communication graph, and cooperate to collectively compute global predicates. From a theoretical prospective, population protocols, with the restricted communication and computational power, are probably one of the simplest distributed model one can imagine. Perhaps surprisingly though, solutions to many classical distributed tasks are still possible. Moreover, these solutions often rely on interesting algorithmic ideas for design and interesting probabilistic techniques for analysis, while known lower bound results revolve around complex combinatorial arguments.

Distributed Computing Column 71

Population protocols have been an active area of distributed computing for over a decade, as they are an abstract model of numerous real-world scenarios from sensor networks to biological computing paradigms. For this column, Dan Alistarh and Rati Gelashvili provide a timely overview of recent results on population protocols, focusing especially on the case when each agent in the system can have more than a constant amount of local memory. Several key building blocks are presented, followed by applications of these primitives, in an accessible way that conveys the excitement of fast-moving developments in the area.