Evaluation of a multidisciplinary, multimodal pain management protocol following pancreas transplantation.

INTRODUCTION: Patients undergoing solid-organ transplantation demonstrate pain arising from both the surgical intervention and pre-existing comorbidities. High levels of opioid use both pre- and post-transplant are associated with unfavorable transplant outcomes. Patient education, multimodal therapy, and discharge planning have all been demonstrated to reduce opioid use after transplant. METHODS: This is a single-center, retrospective study analyzing patients before and after implementation of a multimodal, multidisciplinary pain management protocol. Morphine milligram equivalents (MMEs) use during the index transplant hospitalization and the need for opioids at discharge was compared between the pre- and post-protocol groups. RESULTS: A total of 52 patients were included in the study, 31 in the pre and 21 in the post-protocol groups. Inpatient MME use was reduced from 135.5 to 67.5 MMEs after protocol implementation. Additionally, the number of patients discharged on opioids following transplant decreased from 90.3% to 47.6%. Pain scores, length of stay (LOS), and return of bowel function was not different between groups. CONCLUSION: The implementation of a multimodal, multidisciplinary pain management protocol significantly decreased opioid use during the post-surgical hospitalization and in the 6 months following transplantation. A combination of non-opioid analgesics, patient education, and discharge planning can be beneficial elements in pancreas transplant pain management.

Interfacility Transfer for Nonelective Cholecystectomy in High MELD Patients: An ACS-NSQIP Analysis.

INTRODUCTION: Interfacility transfer to a referral center is often considered for patients with liver disease undergoing nonelective cholecystectomy given management complexities and perioperative risk. We sought to determine the association between the Model for End Stage Liver Disease (MELD) score, transfer frequency, and outcomes in those patients using a national database. MATERIALS AND METHODS: The ACS-NSQIP participant use files were queried for nonelective open or laparoscopic cholecystectomy from 2016 to 2018. Patients were grouped according to low (6-11), intermediate (12-18), or high (>18) MELD. In the high MELD group, patient characteristics and outcomes were compared between transferred and nontransferred patients and multivariate regression was performed to evaluate independent predictors of outcomes. Outcomes included in-hospital mortality, complications, length-of-stay (LOS), and 30-d reoperation and readmission. RESULTS: 30,171 subjects were included. Transfer was more likely as MELD increased (19.5% high versus 12.1% low, P < 0.001). High MELD patients had increased LOS, reoperation, readmission, and mortality rates compared to low MELD. In high MELD patients (n = 1016), those transferred were more likely older, white, obese, and septic. Transferred patients had increased mortality (7.6% versus 4.2%, P = 0.044), LOS, reoperation, and complications. After controlling for differences between transferred and nontransferred patients, transfer status was not independently associated with mortality (OR = 1.593, P = 0.177), postoperative complications or LOS, but was associated with increased risk for reoperation. Sepsis and laparoscopic surgery were independently associated with higher and lower mortality, respectively. CONCLUSIONS: Transfer status is not independently associated with mortality, postoperative complications, or prolonged LOS, suggesting patients with advanced liver disease undergoing acute cholecystectomy may not benefit from interfacility transfer.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

How Does the Evolution of Universal Ecological Traits Affect Population Size? Lessons from Simple Models.

This article argues that adaptive evolutionary change in a consumer species should frequently decrease (and maladaptive change should increase) population size, producing adaptive decline. This conclusion is based on analysis of multiple consumer-resource models that examine evolutionary change in consumer traits affecting the universal ecological parameters of attack rate, conversion efficiency, and mortality. Two scenarios are investigated. In one, evolutionary equilibrium is initially maintained by opposing effects on the attack rate and other growth rate parameters; the environment or trait is perturbed, and the trait then evolves to a new (or back to a previous) equilibrium. Here evolution exhibits adaptive decline in up to one-half of all cases. The other scenario assumes a genetic perturbation having purely fitness-increasing effects. Here adaptive decline in the consumer requires that the resource be self-reproducing and overexploited and requires a sufficient increase in the attack rate. However, if the resource exhibits adaptive defense via behavior or evolution, adaptive decline may characterize consumer traits affecting all parameters. Favorable environmental change producing parameter shifts similar to those produced by adaptive evolution has similar counterintuitive effects on consumer population size. Many different food web models have already been shown to exhibit such counterintuitive changes in some species.

Comparison of glycemic control after pancreas transplantation for Type 1 and Type 2 diabetic recipients at a high volume center.

INTRODUCTION: The number of pancreas transplants (PTX) in patients with Type 2 diabetes (T2DM) has increased in response to excellent outcomes in appropriately selected patients. Not all pancreas transplant centers share an enthusiasm for performing PTX for T2DM out of concern for increased complication rates. This study aims to clarify the characteristics of T2DM recipients with successful outcomes to clarify which candidates are more suitable for PTX as means of maximizing access to this highly effective therapy for Type 2 patients. METHODS & RESULTS: At MedStar Georgetown Transplant Institute, 50 patients underwent pancreas transplant between 2013 and 2016. Based on patient characteristics, 38 (78%) were categorized as T1DM, and 11 (22%) were considered T2DM. One case was excluded due to early graft loss. The estimated age of diabetes onset was significantly different between T1DM and T2DM cohorts (13 years vs. 29 years, P < .001). T2DM patients had significantly higher preoperative C-peptide levels (4.11 vs. 0.05, P < .001). Preoperative HbA1c, preoperative Body Mass Index (BMI), number of diabetic complications, and hemodialysis status were similar between both groups. At 2-year follow-up, there was no statistical difference in glycemic control between the two groups (T1DM vs. T2DM). Infectious complications and readmission rates were similar. Other trends that did not meet statistical significance included T1DM group with a slightly higher mortality and re-intervention rate. The T2DM group demonstrated higher BMI, higher rejection rates, and higher short-term postoperative insulin requirements. Graft survival was 95% and 82% for T1 and T2DM at 2 years post-transplant, respectively. CONCLUSION: Successful PTX in T1DM and T2DM recipient groups resulted in comparable glycemic control at 2-year post-transplant follow-up. T2DM group had a trend toward higher BMI as well as higher rates of rejection, temporary insulin requirement and graft failure, although none of these trends reached statistical significance. These results suggest that strict classification of T1 and T2DM by itself may not be relevant to achieving excellent outcomes in pancreas transplantation and, therefore, patient selection for PTX should not be based primarily on this classification.

The incidence of fungal infections in pancreas transplant recipients in the absence of systemic antifungal prophylaxis.

BACKGROUND: There is a lack of high-level evidence identifying meaningful outcomes and the place in therapy for systemic perioperative antifungal prophylaxis (ppx) in pancreas transplant recipients. As our program does not routinely utilize systemic perioperative antifungal ppx in pancreas transplant recipients, we assessed the incidence of post-transplant infectious complications. METHODS: This was a single-center, retrospective cohort study of consecutive adult pancreas transplant recipients between 01/2016 and 04/2018 to describe the incidence of fungal infections. Patients with a history of previous simultaneous pancreas-kidney (SPK) transplant, HIV, or unexplained use of antifungal ppx after transplantation were excluded. The primary outcome was the incidence of fungal infections within 3 months after transplantation. RESULTS: After screening 60 patients, 56 met inclusion criteria. Within 3 months post-transplantation, two (3.6%) patients had a positive fungal culture requiring systemic antifungal treatment. The sources for infection in both cases were intra-abdominal fluid cultures, positive for Candida albicans. Both patients were treated with fluconazole. Allograft-related outcomes included a 6-month pancreas graft survival of 91.1% and pancreas transplant rejection incidence of 10.7%. CONCLUSION: In this single-center experience, pancreas transplant recipients not receiving systemic antifungal ppx had similar infectious and graft-related outcomes to what is reported in literature.

Does consumption rate scale superlinearly?

Arising from S. Pawar, A. I. Dell & V. M. Savage 486, 485-489 10.1038/nature11131(2012)A recent paper by Pawar and colleagues has provided important insights into the consequences of foraging behaviour for food-web dynamics. One notable pattern predicted by their analysis is that consumption rate (c) scales superlinearly (cm(1.16)) with consumer body mass (m) in three-dimensional (3D), but not two-dimensional (2D), foraging spaces. Although we feel that the authors should be applauded for this interesting contribution, we argue that their result is not consistent with established life-history theory. To resolve this contradiction, progress in both fields is probably required, including new empirical studies in which consumption rate, metabolism and dimensionality are examined directly under natural conditions.

Quality of life after pancreas transplantation: time to look again.

PURPOSE OF REVIEW: To summarize the existing body of literature regarding quality of life after pancreas transplantation, discuss the limitations of existing studies and make an argument for the need for future investigation on this important topic using standard verifiable instruments and utility measurements. RECENT FINDINGS: Reinvigorating support for pancreas transplantation as a life-extending and quality-of-life-enhancing treatment for complicated diabetes mellitus remains a work in progress. Over the past two decades, improvements in surgical management, donor selection, recipient selection and immunosuppression have dramatically improved patient and graft outcomes, achieving durable restoration of normal glucose homeostasis in over 90% of patients. These significant advances in the field of pancreas transplantation have presumably had a positive effect on quality of life of pancreas recipients in the current era; however, this remains unconfirmed. SUMMARY: Technical success in pancreas transplantation has improved dramatically since quality of life was last vigorously investigated in pancreas transplant recipients. Comprehensive review of the literature demonstrates the need and potential usefulness of further study substantiating quality of life benefit after pancreas transplantation, as it remains one of the primary considerations for this procedure.

The road less traveled: how to grow a pancreas transplant program.

PURPOSE OF REVIEW: The volume of pancreas transplants performed annually in the United States (US) has steadily declined for more than a decade. In the face of this negative trend, efforts at several centers are underway to expand their pancreas transplant volumes through alterations in the structure and function of their pancreas transplant programs. We highlight these programmatic changes and emphasize the culture and characteristics of these high volume centers to serve as models for other centers to emulate. As the results of modern-day pancreas transplantation are excellent and continue to improve, pancreas transplant remains an outstanding option for selected patients suffering from diabetes mellitus and end stage renal disease (ESRD) or symptomatic hypoglycemic events (SHEs). Through strong leadership commitment and programmatic restructuring, the transformation of low-volume pancreas transplant centers into high-volume programs is achievable without the need for cost-prohibitive investment. RECENT FINDINGS: Multiple examples may be cited of transplant centers reinvigorating their pancreas transplant programs, increasing their pancreas transplant evaluations and transplant rates, through personnel reorganization and operational restructuring. As a means of providing a roadmap to encourage other transplant centers to re-energize their pancreas transplant programs, we will outline strategies that can be readily instituted to transform a pancreas transplant program, and delineate the basic steps that any transplant center can take to achieve high-volume success. SUMMARY: The negative trends in access to pancreas transplantation in the US may ultimately be addressed by low-volume pancreas transplant programs re-committing themselves through easily achievable institutional changes without substantial added capital investment, thereby maximizing access to pancreas transplantation for their diabetic patients and maintaining excellent outcomes.

Hydra effects in stable communities and their implications for system dynamics.

A hydra effect occurs when the mean density of a species increases in response to greater mortality. We show that, in a stable multispecies system, a species exhibits a hydra effect only if maintaining that species at its equilibrium density destabilizes the system. The stability of the original system is due to the responses of the hydra-effect species to changes in the other species' densities. If that dynamical feedback is removed by fixing the density of the hydra-effect species, large changes in the community make-up (including the possibility of species extinction) can occur. This general result has several implications: (1) Hydra effects occur in a much wider variety of species and interaction webs than has previously been described, and may occur for multiple species, even in small webs; (2) conditions for hydra effects caused by predators (or diseases) often differ from those caused by other mortality factors; (3) introducing a specialist or a switching predator of a hydra-effect species often causes large changes in the community, which frequently involve extinction of other species; (4) harvest policies that attempt to maintain a constant density of a hydra-effect species may be difficult to implement, and, if successful, are likely to cause large changes in the densities of other species; and (5) trophic cascades and other indirect effects caused by predators of hydra-effect species can exhibit amplification of effects or unexpected directions of change. Although we concentrate on systems that are originally stable and models with no stage-structure or trait variation, the generality of our result suggests that similar responses to mortality will occur in many systems without these simplifying assumptions. In addition, while hydra effects are defined as responses to altered mortality, they also imply counterintuitive responses to changes in immigration and other parameters affecting population growth.

Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors.

OBJECTIVES: We report single center experience on the outcome and toxicity of SBRT alone or in combination with surgery for inoperable primary and metastatic liver tumors between 2007 and 2014. PATIENTS AND METHODS: Patients with 1-4 hepatic lesions and tumor diameter ≤9 cm received SBRT at 46.8Gy ± 3.7 in 4-6 fractions. The primary end point was local control with at least 6 months of radiographic followup, and secondary end points were toxicity and survival. RESULTS: Eighty-seven assessable patients (114 lesions) completed liver SBRT for hepatoma (39) or isolated metastases (48) with a median followup of 20.3 months (range 1.9-64.1). Fourteen patients underwent liver transplant with SBRT as a bridging treatment or for tumor downsizing. Eight patients completed hepatic resections in combination with planned SBRT for unresectable tumors. Two-year local control was 96% for hepatoma and 93.8% for metastases; it was 100% for lesions ≤4 cm. Two-year overall survival was 82.3% (hepatoma) and 64.3% (metastases). No incidence of grade >2 treatment toxicity was observed. CONCLUSION: In this retrospective analysis we demonstrate that liver SBRT alone or in combination with surgery is safe and effective for the treatment of isolated inoperable hepatic malignancies and provides excellent local control rates.

The evolutionary and behavioral modification of consumer responses to environmental change.

How will evolution or other forms of adaptive change alter the response of a consumer species' population density to environmentally driven changes in population growth parameters? This question is addressed by analyzing some simple consumer-resource models to separate the ecological and evolutionary components of the population's response. Ecological responses are always decreased population size, but evolution of traits that have effects on both resource uptake rate and another fitness-related parameter may magnify, offset, or reverse this population decrease. Evolution can change ecologically driven decreases in population size to increases; this is likely when: (1) resources are initially below the density that maximizes resource growth, and (2) the evolutionary response decreases the consumer's resource uptake rate. Evolutionary magnification of the ecological decreases in population size can occur when the environmental change is higher trait-independent mortality. Such evolution-driven decreases are most likely when uptake-rate traits increase and the resource is initially below its maximum growth density. It is common for the difference between the new eco-evolutionary equilibrium and the new ecological equilibrium to be larger than that between the original and new ecological equilibrium densities. The relative magnitudes of ecological and evolutionary effects often depend sensitively on the magnitude of the environmental change and the nature of resource growth.

Is feedback control effective for ecosystem-based fisheries management?

We investigate the effects of species interactions on the robustness of feedback control of the harvesting of prey species. We consider the consequences of feedback control of fishing effort. If a prey species is exploited, increasing fishing effort decreases predator abundance more than it does the prey abundance. Feedback control of fishing effort may cause the extinction of the predator, even if the prey population is well controlled. Even when fishing effort is controlled by predator density, it is difficult for the fishery and the predator to coexist, and, if they do so, the system exhibits complex dynamic behaviors. If the predator and fishery coexist, feedback control of fishing effort converges to a stable equilibrium, a synchronous cycle, or an asynchronous cycle. In the last case, the system undergoes more complex cycling with a longer period than that when the fishing effort is kept constant. These analyses suggest that there is no effective strategy that is robust against measurement errors, process errors and complex interactions in ecosystem dynamics.

An Initial Analysis of the Baseline Levels of Dd-cfDNA After Pancreas Transplantation: A Prospective Study From High-volume Centers in the United States.

Pancreas transplantation offers patients with diabetes an opportunity for glucose homeostasis. Current blood tests to surveil for rejection have poor sensitivity and specificity for identifying rejection, and pancreas biopsies are challenging and associated with morbidity and graft loss. Donor-derived cell-free DNA (dd-cfDNA) is shed from transplanted organs and detectable in peripheral blood. Thus, a potential dd-cfDNA blood test assessing rejection would be clinically advantageous. Methods: One hundred eighty-one dd-cfDNA samples (n) were collected from 77 patients (N) up to 132 mo posttransplant. Results: The median dd-cfDNA level among all subjects was 0.28% (0.13%, 0.71%). In simultaneous pancreas-kidney (SPK) transplant recipients, the median dd-cfDNA level was 0.29% (0.13%, 0.71%), and it was 0.23% (0.08%, 0.71%) in pancreas transplant alone (PTA) recipients. When isolating for when without infection or rejection, the median dd-cfDNA level was 0.28% (0.13%, 0.64%) for SPK and 0.20% (0.00%, 0.32%) for PTA. Both transplant types approached 1.0% ≤1 mo posttransplant followed by a decrease in median dd-cfDNA. During episodes of rejection or infection, median dd-cfDNA levels were greater among all transplant types. Conclusions: The mean dd-cfDNA level for all pancreas transplant recipients is <1.0%, consistent with the published kidney transplant rejection threshold (>1.0%), regardless of SPK or PTA. Early posttransplant dd-cfDNA levels are transiently higher than later measurements. Dd-cfDNA elevation also correlates with rejection and infection and thus is a promising biomarker for surveilling pancreas transplant dysfunction.

Harvesting creates ecological traps: consequences of invisible mortality risks in predator-prey metacommunities.

Models of two-patch predator-prey metacommunities are used to explore how the global predator population changes in response to additional mortality in one of the patches. This could describe the dynamics of a predator in an environment that includes a refuge area where that predator is protected and a spatially distinct ("risky") area where it is harvested. The predator's movement is based on its perceived fitness in the two patches, but the risk from the additional mortality is potentially undetectable; this often occurs when the mortality is from human harvesting or from a novel type of top predator. Increases in undetected mortality in the risky area can produce an abrupt collapse of either the refuge population or of the entire predator population when the mortality rate exceeds a threshold level. This is due to the attraction of the risky patch, which has abundant prey due to its high predator mortality. Extinction of the refuge predator population does not occur when the refuge patch has a higher maximum per capita predator growth rate than the exploited patch because the refuge is then more attractive when the predator is rare. The possibility of abrupt extinction of one or both patches from high densities in response to a small increase in harvest is often associated with alternative states. In such cases, large reductions in mortality may be needed to avoid extinction in a collapsing predator population, or to reestablish an extinct population. Our analysis provides a potential explanation for sudden collapses of harvested populations, and it argues for more consideration of adaptive movement in designing protected areas.

Community-Based SARS-CoV-2 Testing Using Saliva or Nasopharyngeal Swabs to Compare the Performance of Weekly COVID-19 Screening to Wastewater SARS-CoV-2 Signals.

Multiple studies worldwide have confirmed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected in wastewater. However, there is a lack of data directly comparing the wastewater SARS-CoV-2 RNA concentration with the prevalence of coronavirus disease 2019 (COVID-19) in individuals living in sewershed areas. Here, we correlate wastewater SARS-CoV-2 signals with SARS-CoV-2 positivity rates in symptomatic and asymptomatic individuals and compare positivity rates in two underserved communities in Portland, Oregon to those reported in greater Multnomah County. 403 individuals were recruited via two COVID-19 testing sites over a period of 16 weeks. The weekly SARS-CoV-2 positivity rate in our cohort ranged from 0 to 21.7% and trended higher than symptomatic positivity rates reported by Multnomah County (1.9-8.7%). Among the 362 individuals who reported symptom status, 76 were symptomatic and 286 were asymptomatic. COVID-19 was detected in 35 participants: 24 symptomatic, 9 asymptomatic, and 2 of unknown symptomatology. Wastewater testing yielded 0.33-149.9 viral RNA genomic copies/L/person and paralleled community COVID-19 positive test rates. In conclusion, wastewater sampling accurately identified increased SARS-CoV-2 within a community. Importantly, the rate of SARS-CoV-2 positivity in underserved areas is higher than positivity rates within the County as a whole, suggesting a disproportionate burden of SARS-CoV-2 in these communities.

Surgical Management of Lower Extremity Wounds in the Solid Organ Transplant Patient Population: Surgeon Beware.

Objective: To evaluate our institutional outcomes of surgical management of lower extremity (LE) wounds in the solid organ transplant recipient population. Approach: An 8-year retrospective review was conducted for all solid organ transplantation (SOT) recipients with LE wounds necessitating surgical management at our tertiary limb salvage center. Outcomes of interest included wound healing, surgical treatment, progression to amputation, and amputation level. Factors contributing to amputation progression were analyzed. The article adheres to the Strengthening the Reporting of Observational Studies in Epidemiology statement. Results: Sixty-four SOT recipients underwent surgical management for their LE wounds between 2010 and 2018. Median number of surgeries per patient was 5 (interquartile range = 2-8); 47 of 64 patients (73.4%) underwent amputation, and 17 of 64 patients (26.6%) underwent nonamputation surgical management. In the amputation group, the majority of primary amputations were minor (42/47, 89.4%); 24 of 42 (57.1%) patients progressed to a higher amputation level, 16 of 42 (38.1%) healed after their index procedure, and 2 of 42 (4.8%) were lost to follow-up (LTFU) after their primary minor amputation. Five of 47 (10.6%) patients undergoing amputations required primary below-knee amputations. In the nonamputation group, 15 of 17 (88.2%) healed, 1 of 17 (5.9%) expired, and 1 of 17 (5.9%) was LTFU. Innovation: To identify the outcomes of patients undergoing surgical management for LE wounds after SOT and elucidate clinical factors that impact the rate of limb salvage. Conclusions: This is the first comprehensive analysis of LE wounds in the transplant population. Our analysis indicates high rates of failed minor amputation, and frequent progression to major amputation in SOT patients. Preexisting comorbidities and immunosuppressive regimens complicate limb salvage; therefore, further research is warranted to optimize surgical LE wound management in this population.

Simple life-history omnivory: responses to enrichment and harvesting in systems with intraguild predation.

This article analyzes the nature of top-down and bottom-up effects and alternative states in systems characterized by life-history omnivory. The analysis is based on a three-species food web with intraguild predation (IGP). The top predator population has juvenile and adult stages, which consume the basal resource and the intermediate prey, respectively; the prey consumes only the resource. The per capita reproduction of the adult predators depends on their consumption rate of prey, while the maturation rate of the juvenile predators depends on their resource consumption rate. Enriching the resource can increase or decrease the abundances of one or both of the two consumer species; an increased density is more likely in the intermediate species than in the systems where IGP is not based on stage differences. Alternative states that have or lack the predator occur frequently, particularly when the prey population is capable of reducing the resource to very low densities. These results differ from those of several other recent models of life-history omnivory. They suggest that life-history omnivory may be one of the primary reasons why exploited populations undergo sudden collapses and why collapsed populations fail to recover in spite of large reductions in the exploitation rate.

How does adaptive consumer movement affect population dynamics in consumer-resource metacommunities with homogeneous patches?

This article uses simple models to explore the impact of adaptive movement by consumers on the population dynamics of a consumer-resource metacommunity consisting of two identical patches. Consumer-resource interactions within a patch are described by the Rosenzweig-MacArthur predator-prey model, and these dynamics are assumed to be cyclic in the absence of movement. The per capita movement rate from one patch to the other is an increasing function of the difference between the per capita birth minus death rate in the destination patch and that in the currently occupied patch. Several variations on this model are considered. Results show that adaptive movement frequently creates anti-phase cycles in the two patches; these suppress the predator-prey cycle and lead to low temporal variation of the total population sizes of both species. Paradoxically, even when movement is very sensitive to the fitness difference between patches, perfect synchrony of patches is often much less likely than in comparable systems with random movement. Under these circumstances adaptive movement of consumers often generates differences in the average properties of the two patches. In addition, mean global densities and responses to global perturbations often differ greatly from similar systems with no movement or random movement.