Population Protocols Research Articles

Protocols with constant local storage and unreliable communication

Population protocols are a model of distributed computation intended for the study of networks of independent computing agents with dynamic communication structure. Each agent has a finite number of states, and communication occurs nondeterministically, allowing the involved agents to change their states based on each other's states.In the present paper we study unreliable models based on population protocols and their variations from the point of view of expressive power. We model the effects of message loss. We show that for a general definition of protocols with unreliable communication with constant-storage agents such protocols can only compute predicates computable by immediate observation (IO) population protocols (sometimes also called one-way protocols). Immediate observation population protocols are inherently tolerant to unreliable communication and keep their expressive power under a wide range of fairness conditions. We also prove that a large class of message-based models that are generally more expressive than IO becomes strictly less expressive than IO in the unreliable case.

Hypersensitivity reactions to biologics in children

ABSTRACT Introduction Hypersensitivity reactions (HSRs) have been observed with the use of biologics in children. The management of HSRs in children is mainly based on experiences from the adult population. Recently, data from different centers experienced in managing these reactions, including desensitization in children, have been published, allowing clinicians to have an appropriate global overview and compare results. Areas covered This review highlights the published data on hypersensitivity reactions to biologics in children and drug desensitization protocols adapted to the pediatric population. Expert opinion With regard to HSRs to biologics in children, few data are available. Compared with the adult population, there is a lack of knowledge in the endophenotypes, management and the standardization of protocols including premedication regimens in children. An international consensus is needed to provide clinicians with new insight on how to apply personalized management and to perform tailored desensitization protocols in pediatric populations. Various specialists including allergists, pediatricians, oncologists, hematologists, rheumatologists, and pharmacists, should build a multidisciplinary management team to keep pediatric patients on their best treatment options in the safest manner.

State Complexity of Population Protocols

State Complexity of Population Protocols

On parallel time in population protocols

The parallel time of a population protocol is defined as the average number of required interactions in which an agent in the protocol participates, i.e., the quotient between the total number of interactions required by the protocol and the total number n of agents, or just roughly the number of required rounds, where a round stands for a sequence of n consecutive interactions. This naming triggers an intuition that at least the expected number of parallel steps sufficient to implement a round is O(1). In a single parallel step only mutually independent interactions can be involved. We show that when the transition function of a population protocol is treated as a black box then the expected maximum number of parallel steps necessary to implement a round is Ω(log⁡nlog⁡log⁡n). We also provide a combinatorial argument for a matching upper bound on the expected number of parallel steps under additional assumptions. Further, we extend these bounds by showing that the situation changes dramatically for sequences of m=Ω(nlog⁡n) interactions. Then, the expected number of parallel steps required to implement such sequences is Θ(mn) under the aforementioned additional assumptions. Thus, it asymptotically coincides with the notion of parallel time, i.e., O(mn), for sequences of interactions produced by protocols solving any non-trivial problems requiring Ω(nlog⁡n) interactions.

Symptomatic Venous Thromboembolic Events in COVID-19 Patients after Hospital Discharge: Aspects to Consider.

Venous thromboembolic (VTE) events have been increasingly reported in patients with coronavirus disease 2019 (COVID-19) after hospital discharge. Acute pulmonary embolism (PE) is the most frequent type of post-discharge VTE complication. Levels of procoagulants (fibrinogen, factor VIII, von Willebrand factor), and D-dimer are higher during the SARS-CoV-2 infection. Patients with more severe inflammatory and procoagulant response experience higher VTE rates during hospitalization, while the risk after hospital discharge have not been well characterized. The incidence of VTE events following hospitalization is heterogeneous, ranging from low (3.1 per 1000 discharges), to 1.8%, which appears higher than for other medical condition. This discrepancy was partially explained by the differences in VTE screening and follow-up strategies, and by the period when the information about the VTE was collected. These data were based mainly on observational and retrospective studies; however, evolving data are to come after the completion of the prospective trials. The current guidelines do not recommend routine post-hospital VTE prophylaxis for COVID-19 patients but recommend it for all hospitalized adults. A careful risk-benefit assessment of VTE probability should be performed, to determine whether an individual patient may merit post-discharge thromboprophylaxis. A score such IMPROVE DD can help identify the patient who will potentially benefit but is also important to consider the bleeding risk and the feasibility. The optimal duration and the type of extended thromboprophylaxis is still under debate (from a minimum of 14 days to a maximum of 42 days), and future studies will help to validate these protocols in different populations. Direct oral anticoagulants (DOACs), warfarin and low molecular weight heparin (LMWH) are recommended, but low doses of DOACs rather than LMVH or warfarin were predominantly used in most patients. Finally, the COVID-19 patients should be educated to recognize and advised to seek urgent medical care should VTE events occur after hospital discharge.

On convergence and threshold properties of discrete Lotka-Volterra population protocols

We study population protocols whose dynamics are modeled by the discrete Lotka-Volterra equations. Such protocols capture the dynamics of some opinion spreading models and generalize the Rock-Paper-Scissors discrete dynamics. Pairwise interactions among agents are scheduled uniformly at random. We consider convergence time and show that any such protocol on an n-agent population converges to an absorbing state in time polynomial in n, w.h.p., when any pair of agents is allowed to interact. When the interaction graph is a star, even the Rock-Paper-Scissors protocol requires exponential time to converge. We study threshold effects with three and more species under interactions between any pair of agents. We prove that the Rock-Paper-Scissors protocol reaches each of its three possible absorbing states with almost equal probability, starting from any configuration satisfying some sub-linear lower bound on the initial size of each species. Thus Rock-Paper-Scissors is a realization of “coin-flip consensus” in a distributed system.

A Retrospective Look at a Cervical Spine Clearance Protocol in Pediatric Trauma Patients at a Level-1 Trauma Center.

Adult studies have demonstrated the efficacy of written protocols for clearance of the cervical spine. However, less than half of recently surveyed pediatric trauma centers report using a documented protocol. Little data exists on such protocols in pediatric populations, but interest remains because of potential reductions in radiation exposure, time to clearance, hospital stay, and specialist referral. However, missed injury can have devastating consequences. The purpose of this study is to examine the efficacy in detecting injury of an implemented cervical spine clearance protocol at a level-1 pediatric trauma hospital. A retrospective review was performed on pediatric patients presenting as activated traumas to the emergency department of a single level-1 pediatric trauma hospital between May 2010 and October 2018. This institution has utilized a written cervical spine clearance protocol throughout this time. Presence of cervical spine injury, documented clearance, cervical spine imaging, and follow-up documentation were reviewed for any missed injuries. There were no missed cervical spine injuries. Five-hundred sixty-three clinically significant cervical spine injuries were identified, representing 16.5% of patients. Of these, 96 were fractures, dislocations, or ligamentous injuries, representing 2.8% of all patients. Most cervical spine clearances were performed by trauma surgery. Advanced imaging of the cervical spine was ordered for 43.2% of patients overall and trended down over time. Documented cervical spine clearance protocols are effective for detection of significant injury in pediatric trauma patients. This study suggests these protocols minimize risk of missed injury and may prevent unnecessary radiation exposure, delayed clearance, prolonged hospitalization, or unnecessary specialist referral. Utilization of a standard written protocol for cervical spine clearance likely prevents missed injury and helps to minimize radiation exposure in pediatric populations. Further research is needed on evaluation and management of pediatric cervical spine trauma.

Verification of Distributed Systems via Sequential Emulation

Sequential emulation is a semantics-based technique to automatically reduce property checking of distributed systems to the analysis of sequential programs. An automated procedure takes as input a formal specification of a distributed system, a property of interest, and the structural operational semantics of the specification language and generates a sequential program whose execution traces emulate the possible evolutions of the considered system. The problem as to whether the property of interest holds for the system can then be expressed either as a reachability or as a termination query on the program. This allows to immediately adapt mature verification techniques developed for general-purpose languages to domain-specific languages, and to effortlessly integrate new techniques as soon as they become available. We test our approach on a selection of concurrent systems originated from different contexts from population protocols to models of flocking behaviour. By combining a comprehensive range of program verification techniques, from traditional symbolic execution to modern inductive-based methods such as property-directed reachability, we are able to draw consistent and correct verification verdicts for the considered systems.

Efficient Assignment of Identities in Anonymous Populations

We consider the fundamental problem of assigning distinct labels to agents in the probabilistic model of population protocols. Our protocols operate under the assumption that the size $n$ of the population is embedded in the transition function. Our labeling protocols are silent, i.e., eventually each agent reaches its final state and remains in it forever, as well as safe, i.e., never update the label assigned to any single agent. We first present a fast, silent and safe labeling protocol for which the required number of interactions is asymptotically optimal, i.e., $O(n \log n/\epsilon)$ w.h.p. It uses $(2+\epsilon)n+O(n^c)$ states, for any $c 1-\frac 1n$, uses $\ge n+\sqrt {n-1} -1$ states. Hence, our protocol is almost state-optimal. We also present a generalization of the protocol to include a trade-off between the number of states and the expected number of interactions. Furthermore, we show that for any silent and safe labeling protocol utilizing $n+t<2n$ states the expected number of interactions required to achieve a valid labeling is $\ge \frac{n^2}{t+1}$.

Development of an Enhanced Recovery Program in Pediatric, Adolescent, and Young Adult Surgical Oncology Patients.

Enhanced recovery after surgery (ERAS) protocols are standardized perioperative treatment plans aimed at improving recovery time in patients following surgery using a multidisciplinary team approach. These protocols have been shown to optimize pain control, improve mobility, and decrease postoperative ileus and other surgical complications, thereby leading to a reduction in length of stay and readmission rates. To date, no ERAS-based protocols have been developed specifically for pediatric patients undergoing oncologic surgery. Our objective is to describe the development of a novel protocol for pediatric, adolescent, and young adult surgical oncology patients. Our protocol includes the following components: preoperative counseling, optimization of nutrition status, minimization of opioids, meticulous titration of fluids, and early mobilization. We describe the planning and implementation challenges and the successes of our protocol. The effectiveness of our program in improving perioperative outcomes in this surgical population could lead to the adaptation of such protocols for similar populations at other centers and would lend support to the use of ERAS in the pediatric population overall.

Time-Optimal Self-Stabilizing Leader Election on Rings in Population Protocols

We propose a self-stabilizing leader election protocol on directed rings in the model of population protocols. Given an upper bound $N$ on the population size $n$, the proposed protocol elects a unique leader within $O(nN)$ expected steps starting from any configuration and uses $O(N)$ states. This convergence time is optimal if a given upper bound $N$ is asymptotically tight, i.e., $N=O(n)$.

A combinatorial characterization of self-stabilizing population protocols

We characterize self-stabilizing functions in population protocols for complete interaction graphs. In particular, we investigate self-stabilization in systems of N finite state agents in which a malicious scheduler selects an arbitrary sequence of pairwise interactions under a global fairness condition. We show a necessary and sufficient condition for self-stabilization. Specifically we show that functions without certain set-theoretic conditions are impossible to compute in a self-stabilizing manner. Our main contribution is in the converse, where we construct a self-stabilizing protocol for all other functions that meet this characterization. Our positive construction uses Dickson's Lemma to develop the notion of the root set, a concept that turns out to fundamentally characterize self-stabilization in this model. We believe it may lend to characterizing self-stabilization in more general models as well.

Comparison of Two Protocols for the Assessment of Maximal Respiratory Pressures: Spanish Society of Pulmonology and Thoracic Surgery Versus American Thoracic Society/European Respiratory Society.

BackgroundThe measurement of maximal respiratory pressures (MRPs) is commonly used to assess respiratory muscle strength. However, in Spain, there is no consensus on which is the most adequate measurement protocol, as theSpanish Society of Pneumology and Thoracic Surgery (SEPAR) protocol differs from the one endorsed by the American Thoracic Society/European Respiratory Society(ATS/ERS). This study compared the absolute and predictive values of maximal expiratory and inspiratory pressures (MEP and MIP) in healthy adults obtained with the two protocols.MethodsA cross-sectional study with a sample of healthy adults was conducted. Lung function and MRPs were assessed. MEP and MIP were measured using a digital manometer according to the SEPAR and ATS/ERS. Protocols were applied in random order by the same trained physiotherapist. The comfort experienced with each protocol was assessed through a short questionnaire. Paired t-tests were used to compare the results from both protocols.ResultsA total of 31 subjects (mean age 35.7±12.4 years; 14 females; FEV1=108.3±10.5%; FVC=103.7±10%) were included. There was a significant difference between MRPs favouring the SEPAR protocol, with the mean difference being 34.9±28.1 cmH2O (p˂0.001) for MEP and 8±11.6 cmH2O (p=0.001) for MIP. ATS/ERS protocol was, however, considered more comfortable than SEPAR (p<0.005).ConclusionsThis study shows that, in healthy adults, higher MRPs are obtained using the SEPAR protocol. Yet, the ATS/ERS protocol is experienced as more comfortable. Future studies are needed to analyse the application of both protocols in other populations and their associated comfort.

Impact of fertility versus mortality control on the demographics of Mastomys natalensis in maize fields.

The multimammate mouse, Mastomys natalensis, is the most common rodent pest species in sub-Saharan Africa. Currently, rodenticides are the preferred method used to reduce the population of rodent pests, but this method poses direct and indirect risks to humans and other non-target species. Fertility control is a promising alternative that has been argued to be a more sustainable and humane method for controlling rodent pests. In this study, we compared the effectiveness of fertility control bait EP-1 (quinestrol (E) and levonorgestrel (P), 10 ppm) and an anticoagulant rodenticide bait (bromadiolone, 50 ppm) on the population dynamics of M. natalensis in maize fields in Zambia during 2 cropping seasons. M. natalensis was the most abundant species in maize fields (77% of total captures). Fertility control reduced the number of juveniles and suppressed population growth of M. natalensis at the end of the 2019-2020 cropping season. The population density initially decreased after rodenticide treatment, but the population rapidly recovered through immigration. None of the treatments influenced maize damage by rodents at germination (F2,67 = 1.626, P = 0.204). Applying the treatments during the maize seeding time was effective at suppressing population growth at the end of the cropping season than application the month before maize seeding. This research indicates that a single-dose delivery of EP-1 and rodenticide have comparable effects on the population dynamics of M. natalensis. These findings are important in developing fertility control protocols for rodent pest populations to reduce maize crop damage and improve yields.

Uniform bipartition in the population protocol model with arbitrary graphs

In this paper, we focus on the uniform bipartition problem in the population protocol model. This problem aims to divide a population into two groups of equal size. In particular, we consider the problem in the context of arbitrary communication graphs. As a result, we investigate the solvability of the uniform bipartition problem with arbitrary communication graphs when agents in the population have designated initial states, under various assumptions such as the existence of a base station, symmetry of the protocol, and fairness of the execution. When the problem is solvable, we present protocols for uniform bipartition. When global fairness is assumed, the space complexity of our solutions is tight.

A survey of size counting in population protocols

The population protocol model describes a network of n anonymous agents who cannot control with whom they interact. The agents collectively solve a computational problem through random pairwise interactions, each agent updating its state in response to seeing the state of the other agent. Population protocols are equivalent to the model of chemical reaction networks, describing abstract chemical reactions such as A+B→C+D, when the latter is subject to the restriction that all reactions have two reactants and two products, and all rate constants are 1. The counting problem is that of designing a protocol so that n agents, all starting in the same state, eventually converge to states where each agent encodes in its state an exact or approximate description of population size n. In this survey paper, we describe recent algorithmic advances on the counting problem.

The case for AI-driven cancer clinical trials – The efficacy arm in silico

Pharmaceutical agents in oncology currently have high attrition rates from early to late phase clinical trials. Recent advances in computational methods, notably causal artificial intelligence, and availability of rich clinico-genomic databases have made it possible to simulate the efficacy of cancer drug protocols in diverse patient populations, which could inform and improve clinical trial design. Here, we review the current and potential use of in silico trials and causal AI to increase the efficacy and safety of traditional clinical trials. We conclude that in silico trials using causal AI approaches can simulate control and efficacy arms, inform patient recruitment and regimen titrations, and better enable subgroup analyses critical for precision medicine.

49 Effect of enhanced recovery protocol in urogynecologic surgery

Enhanced Recovery After Surgery (ERAS) protocols are evidence-based, multidisciplinary and outcome-driven measures developed to provide best practice guidelines for surgical care. Limited data exists to support conventional perioperative interventions of caloric restriction, prolonged immobilization, and liberal administration of fluids and opioids. ERAS protocols for urogynecologic populations are being adopted with limited population and procedure-specific outcome data. Our primary aim was to compare opioid use by patients undergoing major pelvic organ prolapse (POP) surgery before and after implementation of an ERAS protocol. Secondary aims included comparing length of stay and 30-day follow-up characteristics. This ambispective cohort study included a retrospective, pre-ERAS cohort of consecutive patients who underwent major POP surgery starting January 2016. A comprehensive ERAS protocol was implemented in October 2019 (Table 1). A prospective, ERAS cohort consisted of consecutive patients undergoing POP surgery starting in January 2020, 3 months after full implementation of the ERAS protocol. ERAS patients were screened for eligibility and enrolled on the day of surgery. Major POP surgery was defined as including an apical procedure. Demographic and clinical data were abstracted. Descriptive statistics were used for demographic variables. Opioid use was converted to morphine milligram equivalents (MME) and compared between cohorts using the t-test. Other outcomes were compared between groups using t-test or Chi-Square as appropriate. Participants (33 pre-ERAS, 32 ERAS) were similar between cohorts and had mean (SD) age 62.4 (9.7) years, body-mass index 28.9 (4.8) kg/m2, and median (IQR) parity 3 (2-4). Similarly, medical co-morbidities and type of apical POP procedure did not differ between groups. Following ERAS implementation, mean total intra- and post-operative MME decreased (59.4 (31.6) vs 36.6 (20.5), P<0.01). Total discharge prescription MME also decreased (392.3 (88.4) vs 94.6 (61.3), P<0.01). Despite decreased opioid use, post-operative pain scores were not different between groups (Table 2). The ERAS cohort had decreased length of stay and were more likely to be discharged on the day of surgery. Mean number of telephone calls within 30 days of surgery increased (1.0 (1.0) to 2.2 (1.9), P<0.01) while clinic visits, emergency room visits and readmissions did not differ. Implementation of an ERAS protocol in women undergoing major POP surgery resulted in decreased opioid use and length of stay without impacting post-operative pain scores.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Clocked population protocols

We define an extension to the standard population protocol that provides each agent with a clock signal that indicates when the agent has waited long enough for the protocol to have converged. We represent “long enough” as an infinite time interval, and treat the protocol as operating over transfinite time. Over finite time intervals, the protocol behaves as in the standard model. At nonzero limit ordinals, corresponding to clock ticks, the protocol switches to a limit of previous configurations supplemented by a clock signal appearing as an extra component in some of the agents' states. Fairness generalizes to transfinite executions straightforwardly. We show that a clocked population protocol running in less than ωk time for any fixed k≥2 is equivalent in power to a nondeterministic Turing machine with space complexity logarithmic in the population size, and can be simulated using only finitely many clock ticks.

Implementation of a volunteer contact tracing program for COVID-19 in the United States: A qualitative focus group study.

Contact tracing is an important tool for suppressing COVID-19 but has been difficult to adapt to the conditions of a public health emergency. This study explored the experiences and perspectives of volunteer contact tracers in order to identify facilitators, challenges, and novel solutions for implementing COVID-19 contact tracing. As part of a study to evaluate an emergently established volunteer contact tracing program for COVID-19 in New Haven, Connecticut, April-June 2020, we conducted focus groups with 36 volunteer contact tracers, thematically analyzed the data, and synthesized the findings using the RE-AIM implementation framework. To successfully reach cases and contacts, participants recommended identifying clients' outreach preferences, engaging clients authentically, and addressing sources of mistrust. Participants felt that the effectiveness of successful isolation and quarantine was contingent on minimizing delays in reaching clients and on systematically assessing and addressing their nutritional, financial, and housing needs. They felt that successful adoption of a volunteer-driven contact tracing model depended on the ability to recruit self-motivated contact tracers and provide rapid training and consistent, supportive supervision. Participants noted that implementation could be enhanced with better management tools, such as more engaging interview scripts, user-friendly data management software, and protocols for special situations and populations. They also emphasized the value of coordinating outreach efforts with other involved providers and agencies. Finally, they believed that long-term maintenance of a volunteer-driven program requires monetary or educational incentives to sustain participation. This is one of the first studies to qualitatively examine implementation of a volunteer-run COVID-19 contact tracing program. Participants identified facilitators, barriers, and potential solutions for improving implementation of COVID-19 contact tracing in this context. These included standardized communication skills training, supportive supervision, and peer networking to improve implementation, as well as greater cooperation with outside agencies, flexible scheduling, and volunteer incentives to promote sustainability.