Genome Maintenance in Mammalian Stem Cells.

Various stem cells in the body are tasked with maintaining tissue homeostasis throughout the life of an organism and thus must be resilient to intrinsic and extrinsic challenges such as infection and injury. Crucial to these challenges is genome maintenance because a high mutational load and persistent DNA lesions impact the production of essential gene products at proper levels and compromise optimal stem cell renewal and differentiation. Genome maintenance requires a robust and well-regulated DNA damage response suited to maintaining specific niches and tissues. In this review, we explore the similarities and differences between diverse stem cell types derived from (or preceding) all germ layers, including extraembryonic tissues. These cells utilize different strategies, including implementation of robust repair mechanisms, modulation of cell cycle checkpoints best suited to eliminating compromised cells, minimization of cell divisions, and differentiation in response to excessive damage.

Mast cell evaluation in gastrointestinal biopsies: should we be counting? A critical review and practical guide for the surgical pathologist.

Mast cells are residents of the tubular gastrointestinal (GI) tract, where they play an important role in host defence and other vital functions. Dysregulation of mast cells has been implicated in the pathogenesis of several neoplastic, inflammatory, and functional disorders, some of which may manifest with GI symptoms. Surgical pathologists must therefore confront when and how to evaluate GI biopsies for mast cells, and whether such decisions should be based on morphologic criteria, clinical context, or direct request from clinical colleagues. The pathologist's role in evaluation of mast cell infiltrates is best defined in the diagnosis of systemic mastocytosis, where the utility of morphologic assessment coupled with ancillary studies is well established. In contrast, in nonneoplastic mast cell disorders such as mast cell activation syndrome, irritable bowel syndrome, or so-called 'mastocytic enterocolitis', a role for histopathology, if any, is controversial. Despite this, pathologists have seen a sharp increase in requests for mast cell quantification in the latter setting, despite these requests not being supported by published evidence. Moreover, what constitutes a 'normal' number of mast cells in a luminal GI biopsy is not well established. As a result, there is considerable variation in how these requests are handled in practice. This review evaluates and summarizes the published evidence relating to mast cell evaluation in endoscopic GI biopsies in various clinical scenarios, with a goal of providing practical, evidence-based guidance for the surgical pathologist when approached with requests for mast cell quantification in GI biopsies.

Sampling and recovery of infectious SARS-CoV-2 from high-touch surfaces by sponge stick and macrofoam swab.

Effective sampling for severe acute respiratory syndrome 2 (SARS-CoV-2) is a common approach for monitoring disinfection efficacy and effective environmental surveillance. This study evaluated sampling efficiency and limits of detection (LODs) of macrofoam swab and sponge stick sampling methods for recovering infectious SARS-CoV-2 and viral RNA (vRNA) from surfaces. Macrofoam swab and sponge stick methods were evaluated for collection of SARS-CoV-2 suspended in a soil load from 6-in2 coupons composed of four materials: stainless steel (SS), acrylonitrile butadiene styrene (ABS) plastic, bus seat fabric, and Formica. Recovery of infectious SARS-CoV-2 was more efficient than vRNA recovery on all materials except Formica (macrofoam swab sampling) and ABS (sponge stick sampling). Macrofoam swab sampling recovered significantly more vRNA from Formica than ABS and SS, and sponge stick sampling recovered significantly more vRNA from ABS than Formica and SS, suggesting that material and sampling method choice can affect surveillance results. Time since initial contamination significantly affected infectious virus recovery from all materials, with vRNA recovery showing limited to no difference, suggesting that SARS-CoV-2 vRNA can remain detectable after viral infectivity has dissipated. This study showed that a complex relationship exists between sampling method, material, time from contamination to sampling, and recovery of SARS-CoV-2. In conclusion, data show that careful consideration be used when selecting surface types for sampling and interpreting SARS-CoV-2 vRNA recovery with respect to presence of infectious virus.

Evaluation of two methods for detection of viable Bacillus anthracis simulant spores in maritime environmental samples.

Analytical methods exist to detect biothreat agents in environmental samples during a response to biological contamination incidents. However, the coastal zone facilities and assets of the US Coast Guard (USCG), including response boats in diverse geographical areas and maritime environmental conditions, can pose complex and unique challenges for adapting existing analytical detection methods. The traditional culture (TC) and the rapid viability polymerase chain reaction (RV-PCR) methods were evaluated for their compatibility for maritime environmental surface and grab sample analysis to detect spores of Bacillus thuringiensis subspecies kurstaki (Btk), a surrogate for Bacillus anthracis. The representative samples collected from a USCG installation included surfaces, such as aluminum on boats, nonskid tread on decks of watercraft, computer touchscreens, and concrete piers, and grab samples of boat washdown water, soil, vegetation, and gravel from surrounding areas. Replicate samples were spiked with Btk spores at two to three tenfold increasing levels and analyzed. Out of a total of 150 samples collected and analyzed, the TC method gave 10 false-positive and 19 false-negative results, while the RV-PCR method-based analysis resulted in 0 false-positive and 26 false-negative results. An abundance of microbial background and particulates in some samples interfered with true results, while both methods gave similar results for samples with low microbial background and particulates. Improved and high-throughput sample processing methods are needed for analysis of complex environmental samples.

Efficacy of chemical disinfectants against SARS-CoV-2 on high-touch surface materials.

AIMS: This study aimed to provide operationally relevant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface disinfection efficacy information. METHODS AND RESULTS: Three EPA-registered disinfectants (Vital Oxide, Peroxide, and Clorox Total 360) and one antimicrobial formulation (CDC bleach) were evaluated against SARS-CoV-2 on material coupons and were tested using Spray (no touch with contact time) and Spray & Wipe (wipe immediately post-application) methods immediately and 2 h post-contamination. Efficacy was evaluated for infectious virus, with a subset tested for viral RNA (vRNA) recovery. Efficacy varied by method, disinfectant, and material. CDC bleach solution showed low efficacy against SARS-CoV-2 (log reduction < 1.7), unless applied via Spray & Wipe. Additionally, mechanical wiping increased the efficacy of treatments against SARS-CoV-2. The recovery of vRNA post-disinfection suggested that vRNA may overestimate infectious virus remaining. CONCLUSIONS: Efficacy depends on surface material, chemical, and disinfection procedure, and suggests that mechanical wiping alone has some efficacy at removing SARS-CoV-2 from surfaces. We observed that disinfectant treatment biased the recovery of vRNA over infectious virus. SIGNIFICANCE AND IMPACT OF STUDY: These data are useful for developing effective, real-world disinfection procedures, and inform public health experts on the utility of PCR-based surveillance approaches.

Residual antimicrobial coating efficacy against SARS-CoV-2.

AIMS: This study evaluated the residual efficacy of commercially available antimicrobial coatings or films against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on non-porous surfaces. METHODS AND RESULTS: Products were applied to stainless steel or ABS plastic coupons and dried overnight. Coupons were inoculated with SARS-CoV-2 in the presence of 5% soil load. Recovered infectious SARS-CoV-2 was quantified by TCID50 assay. Tested product efficacies ranged from <1.0 to >3.0 log10 reduction at a 2-h contact time. The log10 reduction in recovered infectious SARS-CoV-2 ranged from 0.44 to 3 log10 reduction on stainless steel and 0.25 to >1.67 log10 on ABS plastic. The most effective products tested contained varying concentrations (0.5%-1.3%) of the same active ingredient: 3-(trihydroxysilyl) propyldimethyloctadecyl ammonium chloride. Products formulated with other quaternary ammonium compounds were less effective against SARS-CoV-2 in this test. CONCLUSIONS: The residual antimicrobial products tested showed varied effectiveness against SARS-CoV-2 as a function of product tested. Several products were identified as efficacious against SARS-CoV-2 on both stainless steel and ABS plastic surfaces under the conditions evaluated. Differences in observed efficacy may be due to variation in active ingredient formulation; efficacy is, therefore, difficult to predict based upon listed active ingredient and its concentration. SIGNIFICANCE AND IMPACT: This study highlights the formulation-specific efficacy of several products against SARS-CoV-2 and may inform future development of residual antiviral products for use on non-porous surfaces. The identification of antimicrobial coatings or films showing promise to inactivate SARS-CoV-2 suggests that these products may be worth future testing and consideration.

Vascular Imaging in the Asymptomatic High-risk Cancer Population: A Role for Thrombosis Screening and Therapy Management.

OBJECTIVES: We retrospectively examined the venous thromboembolism (VTE) events diagnosed in the Prophylaxis of High-Risk Ambulatory Cancer Patients Study (PHACS), a multi-center randomized trial, to assess the value of screening vascular imaging for the diagnosis of incidental VTE in high-risk cancer patients. METHODS: A total of 117 asymptomatic cancer patients with a Khorana score ≥3 starting a new systemic chemotherapy regimen were enrolled in a prospective randomized control trial. Patients underwent baseline venous ultrasound (US) of the lower extremities (LEs) and screening contrast-enhanced chest computed tomography (CT). Those without preexisting VTE were then randomized into observation or dalteparin prophylaxis groups and were screened with serial US every 4 weeks for up to 12 weeks and imaged with contrast-enhanced chest CT at 12 weeks. Any additional imaging performed during the study period was also evaluated for VTE. RESULTS: Baseline prevalence of incidental VTE was 9% (n = 10) with 58% percent of VTEs diagnosed by screening US. Incidence of VTE in the randomized phase of the trial was 16% (n = 16) with 21% (n = 10) of patients in the control arm and 12% (n = 6) of patients in the dalteparin arm developing VTE, a non-significant 9% absolute risk reduction (HR = 0.69, 95% CI 0.23-1.89). Sixty-nine percent of these patients were asymptomatic with 31% of patients diagnosed by screening US. CONCLUSIONS: Adding screening US to routine oncologic surveillance CT in high-risk ambulatory cancer patients with a Khorana score ≥3 can lead to increased VTE detection, with potential for decreased morbidity, mortality, and health care spending.

Opportunities and Barriers to Rural Telerobotic Surgical Health Care in 2021: Report and Research Agenda from a Stakeholder Workshop.

Background: There are well-recognized challenges to delivering specialty health care in rural settings. These challenges are particularly evident for specialized surgical health care due to the lack of trained operators in rural communities. Telerobotic surgery could have a significant impact on the rural-urban health care gap, but thus far, the promise of this method of health care delivery has gone unrealized. With the increasing adoption of telehealth over the past year, along with the maturation of telecommunication and robotic technologies over the past 2 decades, a reappraisal of the opportunities and barriers to widespread implementation of telerobotic surgery is warranted. Here we report the outcome of a rural telerobotic stakeholder workshop to explore modern-day issues critical to the advancement of telerobotic surgical health care. Materials and Methods: We assembled a multidisciplinary stakeholder panel to participate in a 2-day Rural Telerobotic Surgery Stakeholder Workshop. Participants had diverse expertise, including specialty surgeons, technology experts, and representatives of the broader telerobotic health care ecosystem, including economists, lawyers, regulatory consultants, public health advocates, rural hospital administrators, nurses, and payers. The research team reviewed transcripts from the workshop with themes identified and research questions generated based on stakeholder comments and feedback. Results: Stakeholder discussions fell into four general themes, including (1) operating room team interactions, (2) education and training, (3) network and security, and (4) economic issues. The research team then identified several research questions within each of these themes and provided specific research strategies to address these questions. Conclusions: There are still important unanswered questions regarding the implementation and adoption of rural telerobotic surgery. Based on stakeholder feedback, we have developed a research agenda along with suggested strategies to address outstanding research questions. The successful execution of these research opportunities will fill critical gaps in our understanding of how to advance the widespread adoption of rural telerobotic health care.

Efficacy of detergent-based cleaning methods against coronavirus MHV-A59 on porous and non-porous surfaces.

This study evaluated the efficacy of detergent-based surface cleaning methods against Murine Hepatitis Virus A59 (MHV) as a surrogate coronavirus for SARS-CoV-2. MHV (5% soil load in culture medium or simulated saliva) was inoculated onto four different high-touch materials [stainless steel (SS), Acrylonitrile Butadiene Styrene plastic (ABS), Formica, seat fabric (SF)]. Immediately and 2-hr post-inoculation, coupons were cleaned (damp wipe wiping) with and without pretreatment with detergent solution or 375 ppm hard water. Results identified that physical removal (no pretreatment) removed >2.3 log10 MHV on ABS, SS, and Formica when surfaces were cleaned immediately. Pretreatment with detergent or hard water increased effectiveness over wet wiping 2-hr post-inoculation; pretreatment with detergent significantly increased (p ≤ 0.05) removal of MHV in simulated saliva, but not in culture media, over hard water pretreatment (Formica and ABS). Detergent and hard water cleaning methods were ineffective on SF under all conditions. Overall, efficacy of cleaning methods against coronaviruses are material- and matrix-dependent; pre-wetting surfaces with detergent solutions increased efficacy against coronavirus suspended in simulated saliva. This study provides data highlighting the importance of incorporating a pre-wetting step prior to detergent cleaning and can inform cleaning strategies to reducing coronavirus surface transmission.

Evaluation of sample processing methods to improve the detection of Bacillus anthracis in difficult sample matrices.

Large area sampling approaches have been developed and implemented by the US Environmental Protection Agency (EPA) to increase sample sizes, and potentially representativeness, in outdoor urban environments (e.g., concrete, asphalt, grass/landscaping). These sampling approaches could be implemented in response to an outdoor biological contamination incident or bioterrorism attack to determine the extent of contamination and for clearance following remediation. However, sample collection over large areas often contains an extensive amount of co-collected debris and native background microorganisms that interfere with the detection of biological threat agents. Sample processing methods that utilize basic laboratory equipment amenable to field deployment were selected and applied to turbid aqueous samples (TAS) to reduce particulates and native environmental organisms prior to culture and rapid viability-polymerase chain reaction (RV-PCR) analytical methods. Bacillus anthracis Sterne (BaS) spores were spiked into TAS collected by soil grab, wet vacuum collection from an outdoor concrete surface, or storm water runoff from an urban parking lot. The implementation of a sample processing method improved the sensitivity of culture and RV-PCR analytical methods for BaS spore detection in soil and wet vacuum TAS samples compared to baseline (minimal to no field processing methods applied). For soil, when the processing method was applied, samples with 15 colony forming units (CFU)/ml (60 CFU/g) and 1.5 CFU/mL (6 CFU/g) BaS spore load were detected using culture and RV-PCR, respectively. Most notably, the processing methods greatly improved the sensitivity of the RV-PCR analytical method for the wet vacuum TAS from no detection at the 1500 CFU/mL BaS spore load level to as low as 1.5 CFU/mL BaS spore load.

Regeneration of per- and polyfluoroalkyl substance-laden granular activated carbon using a solvent based technology.

Per- and polyfluoroalkyl substances (PFAS) are a large class of chemicals widely used for many commercial and industrial applications and have resulted in contamination at sites across globally. Pump-and-treat systems, groundwater extraction, and ex situ treatment using granular activated carbon (GAC) are being implemented, either in full or pilot scale, to treat PFAS-impacted groundwater and drinking water. The only current method of regenerating spent GAC is to reactivate it at temperatures greater than 1000 °C, which requires large amounts of energy and is quite expensive. This research focused on development and demonstration of an effective GAC regeneration technology using a solvent-based method for PFAS-laden GAC used in water treatment. Two different organic solvents (ethanol and isopropyl alcohol) with 0.5% and 1.0% ammonium hydroxide (NH4OH) as a base additive were tested to determine the most effective regenerant solution to remove PFAS from the contaminated GAC. Based on column tests using laboratory-contaminated GAC with perfluorooctanoic acid (PFOA) and perfluorooctanoic sulfonate (PFOS), the solvent-base mix (SBM) of ethanol with 0.5% NH4OH was found to be the optimum performing regenerant solution. The GAC life span assessment showed that solvent-regenerated GAC performed similar to virgin GAC without losing its optimal performance of PFAS sorption. Further, the solvent-regenerated GAC showed optimal performance even after four cycles of solvent regenerations tested using the optimum SBM. Average percent removal in laboratory-contaminated GAC using the optimum SBM was 65% and 93% for PFOS and PFOA, respectively. Four field-spent GAC samples were also regenerated using the optimum SBM. Percent removal from these samples was found to be in range of 55%-68%. The type of GAC used, level of contamination and type of PFAS present, water type and quality, and the presence of co-contaminants may have influenced the removal capacity. Distillation experiments have shown that it is feasible to concentrate the spent solvent prior to disposal, which reduces the amount of PFAS-contaminated solvent waste produced in regeneration cycles.

SemGen: a tool for semantics-based annotation and composition of biosimulation models.

SUMMARY: As the number and complexity of biosimulation models grows, so do demands for tools that can help users understand models and compose more comprehensive and accurate systems from existing models. SemGen is a tool for semantics-based annotation and composition of biosimulation models designed to address this demand. A key SemGen capability is to decompose and then integrate models across existing model exchange formats including SBML and CellML. To support this capability, we use semantic annotations to explicitly capture the underlying biological and physical meanings of the entities and processes that are modeled. SemGen leverages annotations to expose a model's biological and computational architecture and to help automate model composition. AVAILABILITY AND IMPLEMENTATION: SemGen is freely available at https://github.com/SemBioProcess/SemGen. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hospital-specific antibiograms and antibiotic prophylaxis for prostate biopsies: a reexamination of AUA recommendations.

INTRODUCTION: To assess whether standard American Urological Association (AUA) and other recommendations for prostate biopsy prophylaxis provide sufficient coverage of common urinary organisms responsible for post biopsy infections by comparing local antibiograms in Philadelphia-area hospitals. MATERIALS AND METHODS: De-identified culture results derived from antibiograms were collected from six academic and community hospitals in the Philadelphia region. Analysis specifically focused on four major bacterial causes of urinary tract infection following prostate biopsy (Escherichia coli (E. coli), Klebsiella pneumoniae, Proteus mirabilis and Enterococcus faecalis) along with commonly recommended antibiotics including fluoroquinolones (FQ's), trimethoprim/sulfamethoxazole, ceftriaxone, and gentamicin. RESULTS: Bacterial sensitivities to each antibiotic across institutions showed variation in E.coli sensitivities to FQs (p < 0.001), trimethoprim/sulfamethoxazole (p < 0.001), ceftriaxone (p < 0.001) and gentamicin (p < 0.001). Klebsiella pneumoniae and Proteus mirabilis exhibited similar variations. Sensitivity comparisons for Enterococcus faecalis was unable to be performed due to absent or incomplete data across institutions. CONCLUSION: Institutional antibiograms vary within our regional hospitals. Standardized recommendations for commonly used antibiotic prophylaxis such as fluoroquinolones may be inadequate for peri-procedural prostate biopsy prophylaxis based on local resistance patterns. Valuable information about the potential effectiveness of antibiotic prophylaxis for prostate biopsies can be found in local institutional antibiograms, and should be consulted when considering antibiotic prophylaxis for prostate biopsy procedures.

Anticipation of 24 h severe energy restriction increases energy intake and reduces physical activity energy expenditure in the prior 24 h, in healthy males.

Intermittent fasting involves alternating between severely restricted and unrestricted energy intake. Physical activity energy expenditure (PAEE) is reduced during, and energy intake is elevated after, a period of energy restriction, but whether these are altered in anticipation of energy restriction is unknown. The aim of this study was to assess energy intake and PAEE in the 24 h before severe energy restriction. In randomised, counterbalanced order, 14 healthy males completed two 48 h trials over 3 days. On day 1, participants were informed which diet they would receive on day 2; either an energy balanced diet providing 100% (2755 (159) kcal; EB) or an energy restricted diet providing 25% (691 (42) kcal; ER), of their estimated energy requirements. Throughout day 1, ad-libitum energy intake was then determined from researcher-provided breakfast (08:30-09:00), lunch (12:30-13:00), afternoon snacks (14:00-18:00) and dinner (19:30-20:00). On day 2, participants consumed their allocated diet as instructed. On day 3, ad-libitum energy intake was assessed at breakfast (08:30-09:00). PAEE was measured throughout via integrated heart-rate and accelerometry monitors. Energy intake was 6% greater on day 1 (260 (344) kcal; P < 0.05) and 14% greater at breakfast on day 3 (223 (59) kcal; P < 0.05) during ER compared to EB. PAEE was 156 (252) kcal lower on day 1 (P < 0.05) and 239 (391) lower on day 2 (P < 0.05) during ER compared to EB. These behavioural compensations meant that the energy deficit produced by 24 h severe energy restriction was attenuated by 1108 (415) kcal (46%) over the study period (P < 0.0001). These results suggest that compensatory changes in energy intake and PAEE occur before, during and after an acute 24 h period of severe energy restriction, likely lessening the energy deficit created.

Association of meniscal injury to joint space width on standard tibial plateau leveling osteotomy lateral radiographic projections of the canine stifle.

Up to 70% of dogs with cranial cruciate ligament tears have concurrent meniscal injury, and these injuries can increase the risk of developing osteoarthritis and persistent lameness. Studies assessing joint space width on knee radiographs in people have indicated associations between joint space width and meniscal injuries. The aim of this prospective analytical study was to determine if there was an association between stifle joint space width on three different radiographic projections (the standard tibial plateau leveling osteotomy projections and a standing lateral projection) and meniscal injuries identified at surgery in dogs. There was a significant association between dogs with a meniscal tear and the corresponding joint space width on standard tibial plateau leveling osteotomy lateral radiographic projections (P-value = .0028). Based on receiver operator characteristic curve analysis, joint space widths measuring less than 3.43 mm may indicate a meniscal tear, with a corresponding 89.5% specificity and 40.5% sensitivity in dogs weighing 31 kg. Joint space narrowing is seen with meniscal tears in dogs, and radiography may be a noninvasive way to identify meniscal tears prior to surgery.

Inter-scale information flow as a surrogate for downward causation that maintains spiral waves.

A rotor, the rotation center of spiral waves, has been proposed as a causal mechanism to maintain atrial fibrillation (AF) in human. However, our current understanding of the causality between rotors and spiral waves remains incomplete. One approach to improving our understanding is to determine the relationship between rotors and downward causation from the macro-scale collective behavior of spiral waves to the micro-scale behavior of individual components in a cardiac system. This downward causation is quantifiable as inter-scale information flow that can be used as a surrogate for the mechanism that maintains spiral waves. We used a numerical model of a cardiac system and generated a renormalization group with system descriptions at multiple scales. We found that transfer entropy quantified the upward and downward inter-scale information flow between micro- and macro-scale descriptions of the cardiac system with spiral waves. In addition, because the spatial profile of transfer entropy and intrinsic transfer entropy was identical, there were no synergistic effects in the system. Furthermore, inter-scale information flow significantly decreased as the description of the system became more macro-scale. Finally, downward information flow was significantly correlated with the number of rotors, but the higher numbers of rotors were not necessarily associated with higher downward information flow. This finding contradicts the concept that the rotors are the causal mechanism that maintains spiral waves, and may account for the conflicting evidence from clinical studies targeting rotors to eliminate AF.

Prediction and generation of binary Markov processes: Can a finite-state fox catch a Markov mouse?

Understanding the generative mechanism of a natural system is a vital component of the scientific method. Here, we investigate one of the fundamental steps toward this goal by presenting the minimal generator of an arbitrary binary Markov process. This is a class of processes whose predictive model is well known. Surprisingly, the generative model requires three distinct topologies for different regions of parameter space. We show that a previously proposed generator for a particular set of binary Markov processes is, in fact, not minimal. Our results shed the first quantitative light on the relative (minimal) costs of prediction and generation. We find, for instance, that the difference between prediction and generation is maximized when the process is approximately independently, identically distributed.

Unique Information and Secret Key Agreement.

The partial information decomposition (PID) is a promising framework for decomposing a joint random variable into the amount of influence each source variable X i has on a target variable Y, relative to the other sources. For two sources, influence breaks down into the information that both X 0 and X 1 redundantly share with Y, what X 0 uniquely shares with Y, what X 1 uniquely shares with Y, and finally what X 0 and X 1 synergistically share with Y. Unfortunately, considerable disagreement has arisen as to how these four components should be quantified. Drawing from cryptography, we consider the secret key agreement rate as an operational method of quantifying unique information. Secret key agreement rate comes in several forms, depending upon which parties are permitted to communicate. We demonstrate that three of these four forms are inconsistent with the PID. The remaining form implies certain interpretations as to the PID's meaning-interpretations not present in PID's definition but that, we argue, need to be explicit. Specifically, the use of a consistent PID quantified using a secret key agreement rate naturally induces a directional interpretation of the PID. We further reveal a surprising connection between third-order connected information, two-way secret key agreement rate, and synergy. We also consider difficulties which arise with a popular PID measure in light of the results here as well as from a maximum entropy viewpoint. We close by reviewing the challenges facing the PID.

Hidden structures of information transport underlying spiral wave dynamics.

A spiral wave is a macroscopic dynamics of excitable media that plays an important role in several distinct systems, including the Belousov-Zhabotinsky reaction, seizures in the brain, and lethal arrhythmia in the heart. Because the spiral wave dynamics can exhibit a wide spectrum of behaviors, its precise quantification can be challenging. Here we present a hybrid geometric and information-theoretic approach to quantifying the spiral wave dynamics. We demonstrate the effectiveness of our approach by applying it to numerical simulations of a two-dimensional excitable medium with different numbers and spatial patterns of spiral waves. We show that, by defining the information flow over the excitable medium, hidden coherent structures emerge that effectively quantify the information transport underlying the spiral wave dynamics. Most importantly, we find that some coherent structures become more clearly defined over a longer observation period. These findings provide validity with our approach to quantitatively characterize the spiral wave dynamics by focusing on information transport. Our approach is computationally efficient and is applicable to many excitable media of interest in distinct physical, chemical, and biological systems. Our approach could ultimately contribute to an improved therapy of clinical conditions such as seizures and cardiac arrhythmia by identifying potential targets of interventional therapies.

Information Flows? A Critique of Transfer Entropies.

A central task in analyzing complex dynamics is to determine the loci of information storage and the communication topology of information flows within a system. Over the last decade and a half, diagnostics for the latter have come to be dominated by the transfer entropy. Via straightforward examples, we show that it and a derivative quantity, the causation entropy, do not, in fact, quantify the flow of information. At one and the same time they can overestimate flow or underestimate influence. We isolate why this is the case and propose several avenues to alternate measures for information flow. We also address an auxiliary consequence: The proliferation of networks as a now-common theoretical model for large-scale systems, in concert with the use of transferlike entropies, has shoehorned dyadic relationships into our structural interpretation of the organization and behavior of complex systems. This interpretation thus fails to include the effects of polyadic dependencies. The net result is that much of the sophisticated organization of complex systems may go undetected.