IL-35-mediated induction of a potent regulatory T cell population.

Regulatory T cells (T(reg) cells) have a critical role in the maintenance of immunological self-tolerance. Here we show that treatment of naive human or mouse T cells with IL-35 induced a regulatory population, which we call 'iT(R)35 cells', that mediated suppression via IL-35 but not via the inhibitory cytokines IL-10 or transforming growth factor-ß (TGF-ß). We found that iT(R)35 cells did not express or require the transcription factor Foxp3, and were strongly suppressive and stable in vivo. T(reg) cells induced the generation of iT(R)35 cells in an IL-35- and IL-10-dependent manner in vitro and induced their generation in vivo under inflammatory conditions in intestines infected with Trichuris muris and within the tumor microenvironment (B16 melanoma and MC38 colorectal adenocarcinoma), where they contributed to the regulatory milieu. Thus, iT(R)35 cells constitute a key mediator of infectious tolerance and contribute to T(reg) cell-mediated tumor progression. Furthermore, iT(R)35 cells generated ex vivo might have therapeutic utility.

A role for IL-27p28 as an antagonist of gp130-mediated signaling.

The heterodimeric cytokine interleukin 27 (IL-27) signals through the IL-27Rα subunit of its receptor, combined with gp130, a common receptor chain used by several cytokines, including IL-6. Notably, the IL-27 subunits p28 (IL-27p28) and EBI3 are not always expressed together, which suggests that they may have unique functions. Here we show that IL-27p28, independently of EBI3, antagonized cytokine signaling through gp130 and IL-6-mediated production of IL-17 and IL-10. Similarly, the ability to generate antibody responses was dependent on the activity of gp130-signaling cytokines. Mice transgenic for expression of IL-27p28 showed a substantial defect in the formation of germinal centers and antibody production. Thus, IL-27p28, as a natural antagonist of gp130-mediated signaling, may be useful as a therapeutic for managing inflammation mediated by cytokines that signal through gp130.

Chinook salmon diversity contributes to fishery stability and trade-offs with mixed-stock harvest.

Variation among populations in life history and intrinsic population characteristics (i.e., population diversity) helps maintain resilience to environmental change and dampen interannual variability in ecosystem services. As a result, ecological variation, and the processes that generate it, is considered central to strategies for managing risks to ecosystems in an increasingly variable and uncertain world. However, characterizing population diversity is difficult, particularly in large and remote regions, which often prevents its formal consideration in management advice. We combined genetic stock identification of archived scale and tissue samples with state-space run-reconstruction models to estimate migration timing and annual return abundance for eight geographically and genetically distinct Chinook salmon populations within the Canadian portion of the Yukon River. We found that among-population variation in migration timing and return abundances resulted in aggregate return migrations that were 2.1 times longer and 1.4 times more stable than if they had composed a single homogeneous population. We then fit state-space spawner-recruitment models to the annual return abundances to characterize among-population diversity in intrinsic productivity and population size and their consequences for the fisheries they support. Productivity and carrying capacity varied among populations by approximately 2.4-fold (2.9 to 6.9 recruits per spawner) and three-fold (8800 to 27,000 spawners), respectively. This diversity implies an equilibrium trade-off between harvesting of the population aggregate and the conservation of individual populations whereby the harvest rate predicted to maximize aggregate harvests comes at the cost of overfishing ~40% of the populations but with a relatively low risk of extirpating the weakest ones. Our findings illustrate how population diversity in one of the largest salmon-producing river basins in the world contributes to fishery stability and food security in a region where salmon have high cultural and subsistence value. More generally, our work demonstrates the utility of molecular analyses of archived biological material for characterizing diversity in biological systems and its benefits and consequences for trade-offs in decision-making.

Identifying target reference points for harvesting assessment-limited wildlife populations: a case study.

Identifying appropriate strategies for sustainable harvest is a challenge for many terrestrial vertebrate species because of uncertain system dynamics, limited data to inform population models, and potentially conflicting objectives that seek to harvest and maintain populations at desirable levels. The absence of monitoring and assessment infrastructure needed to regularly estimate abundance accentuates this challenge for many species, and limits application of rigorous state-dependent frameworks for decision making that are commonly advocated in natural resource management. Reference points, which define management targets or triggers for changing management, are often used to guide decision-making, but suffer from ambiguity when developed without explicit consideration of uncertainty or trade-offs among competing objectives. We describe an approach for developing unambiguous target reference points for assessment-limited species using structured decision making, and demonstrate the approach to develop target harvest rates for management of fall Wild Turkey (Meleagris gallopavo) harvests in the face of uncertain population and harvest dynamics. We use simulation and decision analyses to identify harvest rates that are optimal for accomplishing explicit management objectives in the face of uncertainty, and harvest rates with robust performance over broad regions of the demographic and harvest model parameter space. We demonstrate that population and harvest parameters commonly uncertain to wildlife managers interact to determine appropriate target harvest rates for Wild Turkeys, and that formally acknowledging a range of plausible values for structurally uncertain parameters results in more conservative target reference points than suggested by previously published studies. The structured decision making framework described here provides a natural conceptual and quantitative framework for extending our approach to develop unambiguous harvest targets for other assessment-limited wildlife populations while formally acknowledging structural uncertainty in system dynamics.

Effects of Peer Mentoring on Self-Efficacy and Hospital Readmission After Inpatient Rehabilitation of Individuals With Spinal Cord Injury: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of intensive peer mentoring on patient-reported outcomes of self-efficacy and unplanned hospital readmissions for persons with spinal cord injury/disease (SCI/D) within the first 6 months after discharge from inpatient rehabilitation. DESIGN: Randomized controlled trial. SETTING: Nonprofit inpatient rehabilitation hospital specializing in care of persons with SCI/D and brain injury. PARTICIPANTS: Patients (N=158) admitted to the SCI/D rehabilitation program whose discharge location was a community setting. Participants (51% with paraplegia and 49% with tetraplegia) were 73% white and 77% men, with a mean age of 38 years. INTERVENTIONS: Participants in the experimental group received initial consult/introduction with a peer support program liaison and were assigned a peer mentor, who met with the participant weekly throughout the inpatient stay and made weekly contact by phone, e-mail, or in person for 90 days postdischarge. Participants also were encouraged to participate in regularly scheduled peer support activities. Nonexperimental group participants were introduced to peer support and provided services only on request. MAIN OUTCOME MEASURES: General Self-efficacy Scale (adapted to SCI/D), project-developed community integration self-efficacy scale, and patient-reported unplanned rehospitalizations. RESULTS: Growth rate for self-efficacy in the first 6 months postdischarge was significantly higher for experimental group participants than nonexperimental group participants. Experimental group participants also had significantly fewer unplanned hospital days. CONCLUSIONS: This study provides evidence that individuals receiving intensive peer mentoring during and after rehabilitation for SCI/D demonstrate greater gains in self-efficacy over time and have fewer days of unplanned rehospitalization in the first 180 days postdischarge. More research is needed to examine the long-term effects of this intervention on health care utilization and the relation between improved health and patient-reported quality of life outcomes.

Evaluating harvest-based control of invasive fish with telemetry: performance of sea lamprey traps in the Great Lakes.

Physical removal (e.g., harvest via traps or nets) of mature individuals may be a cost-effective or socially acceptable alternative to chemical control strategies for invasive species, but requires knowledge of the spatial distribution of a population over time. We used acoustic telemetry to determine the current and possible future role of traps to control and assess invasive sea lampreys, Petromyzon marinus, in the St. Marys River, the connecting channel between Lake Superior and Lake Huron. Exploitation rates (i.e., fractions of an adult sea lamprey population removed by traps) at two upstream locations were compared among three years and two points of entry to the system. Telemetry receivers throughout the drainage allowed trap performance (exploitation rate) to be partitioned into two components: proportion of migrating sea lampreys that visited trap sites (availability) and proportion of available sea lampreys that were caught by traps (local trap efficiency). Estimated exploitation rates were well below those needed to provide population control in the absence of lampricides and were limited by availability and local trap efficiency. Local trap efficiency estimates for acoustic-tagged sea lampreys were lower than analogous estimates regularly obtained using traditional mark-recapture methods, suggesting that abundance had been previously underestimated. Results suggested major changes would be required to substantially increase catch, including improvements to existing traps, installation of new traps, or other modifications to attract and retain more sea lampreys. This case study also shows how bias associated with telemetry tags can be estimated and incorporated in models to improve inferences about parameters that are directly relevant to fishery management.

Academic Health Center-Rural Community Collaborations: 'Healthy Linkages' to Improve the Health of Rural Populations.

PURPOSE: The purpose of this paper is to describe an extant theoretical model framing Mississippi Healthy Linkages, a successful academic-community partnership undergirding an emergency department (ED) diversion program. DESCRIPTION: The partnership between the University of Mississippi Medical Center, Mississippi State Department of Health, and Federally Qualified Health Centers is grounded in the Structuration Model of Collaboration and utilizes collective action to support an organized system of care linking academic and community care settings to address health disparities, particularly for rural and vulnerable populations. ASSESSMENT: Partners identified three interconnected segments of an integrated patient referral system to improve patient-level care, including galvanization of primary care services for ED patients, connection of primary care patients to specialty care, and linking ED patients with aftercare services. CONCLUSIONS: This academic-community partnership has significant benefits for linking health care and public health systems to address remote and vulnerable population health issues and serves as a model to be replicated in other areas of the United States, particularly in the Southeast and in rural areas.

Activity-based therapy for recovery of walking in individuals with chronic spinal cord injury: results from a randomized clinical trial.

OBJECTIVE: To examine the effects of activity-based therapy (ABT) on neurologic function, walking ability, functional independence, metabolic health, and community participation. DESIGN: Randomized controlled trial with delayed treatment design. SETTING: Outpatient program in a private, nonprofit rehabilitation hospital. PARTICIPANTS: Volunteer sample of adults (N=48; 37 men and 11 women; age, 18-66y) with chronic (≥12mo postinjury), motor-incomplete (ASIA Impairment Scale grade C or D) spinal cord injury (SCI). INTERVENTIONS: A total of 9h/wk of ABT for 24 weeks including developmental sequencing; resistance training; repetitive, patterned motor activity; and task-specific locomotor training. Algorithms were used to guide group allocation, functional electrical stimulation utilization, and locomotor training progression. MAIN OUTCOME MEASURES: Neurologic function (International Standards for Neurological Classification of Spinal Cord Injury); walking speed and endurance (10-meter walk test, 6-minute walk test, and Timed Up and Go test); community participation (Spinal Cord Independence Measure, version III, and Reintegration to Normal Living Index); and metabolic function (weight, body mass index, and Quantitative Insulin Sensitivity Check). RESULTS: Significant improvements in neurologic function were noted for experimental versus control groups (International Standards for Neurological Classification of Spinal Cord Injury total motor score [5.1±6.3 vs 0.9±5.0; P=.024] and lower extremity motor score [4.2±5.2 vs -0.6±4.2; P=.004]). Significant differences between experimental and control groups were observed for 10-meter walk test speed (0.096±0.14m/s vs 0.027±0.10m/s; P=.036) and 6-minute walk test total distance (35.97±48.2m vs 3.0±25.5m; P=.002). CONCLUSIONS: ABT has the potential to promote neurologic recovery and enhance walking ability in individuals with chronic, motor-incomplete SCI. However, further analysis is needed to determine for whom ABT is going to lead to meaningful clinical benefits.

Activity-based therapy for recovery of walking in chronic spinal cord injury: results from a secondary analysis to determine responsiveness to therapy.

OBJECTIVE: To gain insight into who is likely to benefit from activity-based therapy (ABT), as assessed by secondary analysis of data obtained from a clinical trial. DESIGN: Secondary analysis of results from a randomized controlled trial with delayed treatment design. SETTING: Outpatient program in a private, nonprofit rehabilitation hospital. PARTICIPANTS: Volunteer sample of adults (N=38; 27 men; 11 women; age, 22-63y) with chronic (≥12mo postinjury), motor-incomplete (American Spinal Injury Association [ASIA] Impairment Scale [AIS] grade C or D) spinal cord injury (SCI). INTERVENTIONS: A total of 9h/wk of ABT for 24 weeks including developmental sequencing; resistance training; repetitive, patterned motor activity; and task-specific locomotor training. Algorithms were used to guide group allocation, functional electrical stimulation utilization, and locomotor training progression. MAIN OUTCOME MEASURES: Walking speed and endurance (10-meter walk test and 6-minute walk test) and functional ambulation (timed Up and Go test). RESULTS: This secondary analysis identified likely responders to ABT on the basis of injury characteristics: AIS classification, time since injury, and initial walking ability. Training effects were the most clinically significant in AIS grade D participants with injuries <3 years in duration. This information, along with information about preliminary responsiveness to therapy (gains after 12wk), can help predict the degree of recovery likely from participation in an ABT program. CONCLUSIONS: ABT has the potential to promote neurologic recovery and enhance walking ability in individuals with chronic, motor-incomplete SCI. However, not everyone with goals of walking recovery will benefit. Individuals with SCI should be advised of the time, effort, and resources required to undertake ABT. Practitioners are encouraged to use the findings from this trial to assist prospective participants in establishing realistic expectations for recovery.

Maximizing research relevance to enhance knowledge translation.

This supplement focuses on an important issue in rehabilitation medicine: how to maximize research relevance in order to enhance knowledge translation into clinical practice. Authors provide insights into issues and barriers impacting effective translation of evidence into practice and provide useful guidance for rehabilitation researchers and practitioners on how to structure lines of inquiry to enhance clinical relevance. While this supplement will provide meaningful information to rehabilitation researchers, the content will also be of interest to clinicians, consumers of rehabilitation services, and reviewers for journals featuring rehabilitation research.

Instilling a research culture in an applied clinical setting.

This article offers a framework and practical advice to nurture development of a research culture within a clinical setting. Information is presented on research education, infrastructure, and helping clinicians develop a scientific mindset. Economical ways to facilitate a scientist-practitioner approach to clinical practice are described, as well as metrics to gauge the success of these efforts.

Emergency department triage of low acuity patients to a Federally Qualified Health Center.

Many emergency departments (ED) are experiencing ever increasing volumes as they serve as a safety net for patients without established access to primary care. Impending physician shortages, our aging population, and recent changes in national healthcare policy are expected to further exacerbate this situation and worsen ED overcrowding. These conditions could result in a dilution of ED resources and significantly impact the ability of emergency personnel to provide quality care for patients with serious illnesses. Previous studies have demonstrated that low acuity patients without emergencies can be safely and legally identified in triage and can be sent away from the ED for further outpatient treatment and evaluation. However, without a specific designated clinic follow up, these patients often fail to get the appropriate care required. In this study, we couple the ED medical screening exam process with a timely medical referral system to a local Federally Qualified Healthcare Clinic (FQHC). These referred patients were monitored for subsequent success in satisfaction with their primary care needs and their rate of recidivism to the ED. Most of the non-emergent patients who were judged to be appropriate to refer to the FQHC were satisfied with their medical screening process (89%) and most elected to attend the same day clinic appointment at the FQHC (85%). Only 17% of these patients who were referred out of our ED returned to be seen in our ED within the three-month interval. We concluded that referring low acuity patients out of the emergency department to a primary care clinic setting provided an opportunity for these patients to establish a medical home for future access to non-emergent health care.

Activity-based Therapies in Spinal Cord Injury:: Clinical Focus and Empirical Evidence in Three Independent Programs.

This article summarizes presentations of a symposium examining the potential impact of activity-based therapies (ABT) in promoting neurological and functional recovery after spinal cord injury (SCI). The symposium addressed 3 key questions concerning activity-based therapy in SCI: (1) What clinical approaches are used? (2) Is there empirical evidence supporting efficacy of ABT in promoting neurological recovery and improving overall function, health, and quality of life? (3) What are the issues related to long-term viability of ABT?

Peer mentoring reduces unplanned readmissions and improves self-efficacy following inpatient rehabilitation for individuals with spinal cord injury.

OBJECTIVE: Evaluate effectiveness of peer interventions on self-efficacy, unplanned hospital readmissions, and quality of life for patients with spinal cord injury (SCI) undergoing inpatient rehabilitation. DESIGN: Interrupted time-series analysis (ITSA) examined effects of peer interventions on unplanned readmissions. Intervention variables added to ITSA regression examined relationships with exposure to peer interventions. Heterogeneity of treatment effects (HTE) analysis examined differences in intervention effectiveness for patients with quadriplegia and paraplegia. SETTING: Rehabilitation hospital specializing in SCI and brain injury. PARTICIPANTS: SCI inpatients (n = 1117) admitted for rehabilitation whose discharge location was home (77% male, 71% Caucasian, mean age 38.2 (SD 16.8)). A subsample of 799 patients participated in secondary analyses examining relationship between peer interventions, readmissions, changes in patient-reported outcomes, and HTE. INTERVENTIONS: One-to-one mentoring and participation in peer-led self-management classes. MAIN OUTCOME MEASURES: Unplanned readmissions, general self-efficacy (GSE), and depressive symptoms 30, 90, and 180 days post discharge; satisfaction with life at 180 days. RESULTS: After implementing the peer interventions, we observed a significant decrease in both level and slope of number of patients readmitted, and level only of unplanned hospital days 30-days post-discharge. Reduction in the number of patients and unplanned hospital days was associated with number of peer visits but not peer-led education classes attended. Higher self-efficacy (GSE) was associated with greater exposure to peer mentoring, and a significant relationship between improvement in GSE and reduced hospital readmissions was observed. CONCLUSIONS: One-to-one peer mentoring improves self-efficacy and reduces unplanned hospital readmissions following inpatient rehabilitation for persons with SCI.

The Beverage Hydration Index: Influence of Electrolytes, Carbohydrate and Protein.

The beverage hydration index (BHI) facilitates a comparison of relative hydration properties of beverages using water as the standard. The additive effects of electrolytes, carbohydrate, and protein on rehydration were assessed using BHI. Nineteen healthy young adults completed four test sessions in randomized order: deionized water (W), electrolytes only (E), carbohydrate-electrolytes (C + E), and 2 g/L dipeptide (alanyl-glutamine)-electrolytes (AG + E). One liter of beverage was consumed, after which urine and body mass were obtained every 60 min through 240 min. Compared to W, BHI was higher (p = 0.007) for C + E (1.15 ± 0.17) after 120 min and for AG + E (p = 0.021) at 240 min (1.15 ± 0.20). BHI did not differ (p > 0.05) among E, C + E, or AG + E; however, E contributed the greatest absolute net effect (>12%) on BHI relative to W. Net fluid balance was lower for W (p = 0.048) compared to C + E and AG + E after 120 min. AG + E and E elicited higher (p < 0.001) overall urine osmolality vs. W. W also elicited greater reports of stomach bloating (p = 0.02) compared to AG + E and C + E. The addition of electrolytes alone (in the range of sports drinks) did not consistently improve BHI versus water; however, the combination with carbohydrate or dipeptides increased fluid retention, although this occurred earlier for the sports drink than the dipeptide beverage. Electrolyte content appears to make the largest contribution in hydration properties of beverages for young adults when consumed at rest.

Regulating hearing aid compatibility of cell phones: results from a national survey.

Accessibility of telecommunication technologies by people who are deaf or hard of hearing has been a critical issue since the invention of the telephone. As both telephone and hearing-aid technologies have evolved, finding compatible solutions has been an ongoing challenge. This paper uses the findings of a longitudinal study to examine the impact of Federal hearing-aid compatibility (HAC) regulations in resolving this problem. The study ran concurrently with the phase-in of Federal Communications Commission regulations requiring that mobile handset manufacturers and wireless service providers make available minimum numbers of cell phones with shielding to reduce electromagnetic interference when cell phones are positioned close to a hearing aid user's ear. These regulations also require package labeling and printed information to assist buyers in selecting a hearing-aid compatible phone. The survey presented here focused on changes in satisfaction with sound quality and ease of finding a hearing-aid compatible mobile handset. Data analysis suggests that the regulations have had limited success, and problems persist for consumers in locating a hearing aid compatible phone. The FCC has requested input on more stringent hearing-aid compatibility requirements; study findings suggest that these changes are not likely to remedy the problem.

Spatial-temporal dynamics of hunter effort for wild turkeys in Michigan.

Wild turkeys (Meleagris gallopavo; hereafter turkeys) are an important game animal whose popularity among hunters has increased in recent decades. Yet, the number of hunters pursuing turkeys appears to be in flux, patterns of hunter abundance have primarily been described at broad spatial scales, and the ability of management to impact hunter numbers in the post-restoration era of management through opportunity for quality hunting is unclear. We used county-scale estimates of turkey hunter numbers collected over a 14-year period (2001-2014) and time-series analyses to evaluate the spatial scales at which spring and fall turkey hunter populations fluctuate, and also used generalized linear mixed models to evaluate whether attributes related to quality turkey hunting explain recent patterns in hunter abundance. We found heterogeneity in turkey hunter population growth at finer spatial scales than has been previously described (i.e., counties and management units), and provide evidence for spatial structuring of hunter population dynamics among counties that did not always correspond with existing management units. Specifically, the directionality of hunter population change displays spatial structure along an east-west gradient in southern Michigan. We also found little evidence that factors providing opportunity for quality turkey hunting had meaningful impacts on recent spatial-temporal patterns of hunter numbers. Our results imply that providing quality turkey hunting opportunities alone may be insufficient for sustaining populations of turkey hunters in the future, and that modern determinants of hunter participation extend beyond the availability of abundant turkey populations. Moreover, our results demonstrate that interpretation of harvest data as indices of abundance for turkey populations is difficult in the absence of hunter effort data, as changes to turkey harvest are a function of potentially fine-scaled changes in populations of hunters, not simply changes to turkey populations.

Modeling fish health to inform research and management: Renibacterium salmoninarum dynamics in Lake Michigan.

Little is known about the interaction between fish pathogens and managed freshwater fish populations. We develop a model of chinook salmon (Oncorhynchus tschawytscha)-Renibacterium salmoninarum (Rs) dynamics based on free-swimming Lake Michigan fish by synthesizing population and epidemiological theory. Using the model, we expose critical uncertainties about the system, identify opportunities for efficient and insightful data collection, and pose testable hypotheses. Our simulation results suggest that hatcheries potentially play an important role in Lake Michigan Rs dynamics, and understanding vertical transmission will be critical for quantifying this role. Our results also show that disease-mediated responses to chinook salmon density need to be considered when evaluating management actions. Related to this, a better understanding of the stock-recruitment relationship and natural mortality rates for wild-spawned fish and the impact of hatchery stocking on recruitment is required. Finally, to further develop models capable of assisting fishery management, fish health surveys ought to be integrated with stock assessment. This is the first time a host-pathogen modeling framework has been applied to managed, freshwater ecosystems, and we suggest that such an approach should be used more frequently to inform other emerging and chronic fish health issues.

Peer-led, transformative learning approaches increase classroom engagement in care self-management classes during inpatient rehabilitation of individuals with spinal cord injury.

OBJECTIVE: Evaluate effects of revised education classes on classroom engagement during inpatient rehabilitation for individuals with spinal cord injury/disease (SCI/D). DESIGN: Multiple-baseline, quasi-experimental design with video recorded engagement observations during conventional and revised education classes; visual and statistical analysis of difference in positive engagement responses observed in classes using each approach. PARTICIPANTS/SETTING: 81 patients (72% male, 73% white, mean age 36 SD 15.6) admitted for SCI/D inpatient rehabilitation in a non-profit rehabilitation hospital, who attended one or more of 33 care self-management education classes that were video recorded. All study activities were approved by the host facility institutional review board. INTERVENTION: Conventional nurse-led self-management classes were replaced with revised peer-led classes incorporating approaches to promote transformative learning. Revised classes were introduced across three subject areas in a step-wise fashion over 15 weeks. OUTCOME MEASURE: Positive engagement responses (asking questions, participating in discussion, gesturing, raising hand, or otherwise noting approval) were documented from video recordings of 14 conventional and 19 revised education classes. RESULTS: Significantly higher average (per patient per class) positive engagement responses were observed in the revised compared to conventional classes (p=0.008). CONCLUSION: Redesigning SCI inpatient rehabilitation care self-management classes to promote transformative learning increased patient engagement. Additional research is needed to examine longer term outcomes and replicability in other settings.