Characterization of topographical effects on macrophage behavior in a foreign body response model.

Current strategies to limit macrophage adhesion, fusion and fibrous capsule formation in the foreign body response have focused on modulating material surface properties. We hypothesize that topography close to biological scale, in the micron and nanometric range, provides a passive approach without bioactive agents to modulate macrophage behavior. In our study, topography-induced changes in macrophage behavior was examined using parallel gratings (250 nm-2 mum line width) imprinted on poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA) and poly(dimethyl siloxane) (PDMS). RAW 264.7 cell adhesion and elongation occurred maximally on 500 nm gratings compared to planar controls over 48 h. TNF-alpha and VEGF secretion levels by RAW 264.7 cells showed greatest sensitivity to topographical effects, with reduced levels observed on larger grating sizes at 48 h. In vivo studies at 21 days showed reduced macrophage adhesion density and degree of high cell fusion on 2 mum gratings compared to planar controls. It was concluded that topography affects macrophage behavior in the foreign body response on all polymer surfaces examined. Topography-induced changes, independent of surface chemistry, did not reveal distinctive patterns but do affect cell morphology and cytokine secretion in vitro, and cell adhesion in vivo particularly on larger size topography compared to planar controls.

A Predictive Thermal Habitat Model for Harbor Seals in the Northwest Atlantic

We analyzed projections of current and future ambient temperatures along the eastern United States in relationship to the thermal tolerance of harbor seals in air. Using the earth systems model (HadGEM2-ES) and representative concentration pathways (RCPs) 4.5 and 8.5, which are indicative of two different atmospheric CO2 concentrations, we were able to examine possible shifts in distribution based on three metrics: current preferences, the thermal limit of juveniles, and the thermal limits of adults. Our analysis focused on average ambient temperatures because harbor seals are least effective at regulating their body temperature in air, making them most susceptible to rising air temperatures in the coming years. Our study focused on the months of May, June, and August from 2041-2060 (2050) and 2061-2080 (2070) as these are the historic months in which harbor seals are known to annually come ashore to pup, breed, and molt. May, June, and August are also some of the warmest months of the year. We found that breeding colonies along the eastern United States will be limited by the thermal tolerance of juvenile harbor seals in air, while their foraging range will extend as far south as the thermal tolerance of adult harbor seals in air. Our analysis revealed that in 2070, harbor seal pups should be absent from the United States coastline nearing the end of the summer due to exceptionally high air temperatures.

Cumulative exposure to traumatic events in older adults.

OBJECTIVES: The present study examined the impact of cumulative trauma exposure on current posttraumatic stress disorder (PTSD) symptom severity in a nonclinical sample of adults in their 60s. The predictive utility of cumulative trauma exposure was compared to other known predictors of PTSD, including trauma severity, personality traits, social support, and event centrality. METHOD: Community-dwelling adults (n = 2515) from the crest of the Baby Boom generation completed the Traumatic Life Events Questionnaire, the PTSD Checklist, the NEO Personality Inventory, the Centrality of Event Scale, and rated their current social support. RESULTS: Cumulative trauma exposure predicted greater PTSD symptom severity in hierarchical regression analyses consistent with a dose-response model. Neuroticism and event centrality also emerged as robust predictors of PTSD symptom severity. In contrast, the severity of individuals' single most distressing life event, as measured by self-report ratings of the A1 PTSD diagnostic criterion, did not add explanatory variance to the model. Analyses concerning event categories revealed that cumulative exposure to childhood violence and adulthood physical assaults were most strongly associated with PTSD symptom severity in older adulthood. Moreover, cumulative self-oriented events accounted for a larger percentage of variance in symptom severity compared to events directed at others. CONCLUSION: Our findings suggest that the cumulative impact of exposure to traumatic events throughout the life course contributes significantly to posttraumatic stress in older adulthood above and beyond other known predictors of PTSD.

Real-Time Decision Making and Aggressive Behavior in Youth: A Heuristic Model of Response Evaluation and Decision (RED).

Considerable scientific and intervention attention has been paid to judgment and decision-making systems associated with aggressive behavior in youth. However, most empirical studies have investigated social-cognitive correlates of stable child and adolescent aggressiveness, and less is known about real-time decision making to engage in aggressive behavior. A model of real-time decision making must incorporate both impulsive actions and rational thought. The present paper advances a process model (response evaluation and decision; RED) of real-time behavioral judgments and decision making in aggressive youths with mathematic representations that may be used to quantify response strength. These components are a heuristic to describe decision making, though it is doubtful that individuals always mentally complete these steps. RED represents an organization of social-cognitive operations believed to be active during the response decision step of social information processing. The model posits that RED processes can be circumvented through impulsive responding. This article provides a description and integration of thoughtful, rational decision making and nonrational impulsivity in aggressive behavioral interactions.

An evaluation of remifentanil-sevoflurane response surface models in patients emerging from anesthesia: model improvement using effect-site sevoflurane concentrations.

INTRODUCTION: We previously reported models that characterized the synergistic interaction between remifentanil and sevoflurane in blunting responses to verbal and painful stimuli. This preliminary study evaluated the ability of these models to predict a return of responsiveness during emergence from anesthesia and a response to tibial pressure when patients required analgesics in the recovery room. We hypothesized that model predictions would be consistent with observed responses. We also hypothesized that under non-steady-state conditions, accounting for the lag time between sevoflurane effect-site concentration (Ce) and end-tidal (ET) concentration would improve predictions. METHODS: Twenty patients received a sevoflurane, remifentanil, and fentanyl anesthetic. Two model predictions of responsiveness were recorded at emergence: an ET-based and a Ce-based prediction. Similarly, 2 predictions of a response to noxious stimuli were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses. RESULTS: While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). However, after termination of the anesthetic, models exhibited a wide range of predictions at emergence (1%-97%). Although wide, the Ce-based predictions of responsiveness were better distributed over a percentage ranking of observations than the ET-based predictions. For the ET-based model, 45% of the patients awoke within 2 min of the 50% model predicted probability of unresponsiveness and 65% awoke within 4 min. For the Ce-based model, 45% of the patients awoke within 1 min of the 50% model predicted probability of unresponsiveness and 85% awoke within 3.2 min. Predictions of a response to a painful stimulus in the recovery room were similar for the Ce- and ET-based models. DISCUSSION: Results confirmed, in part, our study hypothesis; accounting for the lag time between Ce and ET sevoflurane concentrations improved model predictions of responsiveness but had no effect on predicting a response to a noxious stimulus in the recovery room. These models may be useful in predicting events of clinical interest but large-scale evaluations with numerous patients are needed to better characterize model performance.