Noninvasive Cerebral Cooling in a Swine Model of Cardiac Arrest

Objective: Mild cerebral hypothermia improves neurologic outcome in animals resuscitated from cardiac arrest. This study examined whether one practical external cooling method, i.e., local application of ice to the heads and necks of swine, during resuscitation induces cerebral cooling.
Methods: Local external cerebral cooling was examined in a prospective laboratory investigation using 24 female swine in a model of cardiac arrest. The swine were randomized into hypothermia and normothermia groups. Intracerebral temperature was measured in the parietal cortex. Eight minutes after induction of ventricular fibrillation, chest compressions and mechanical ventilation were initiated. The hypothermia group was treated with 1,500 mL of ice in plastic bags applied to the head and neck, while the normothermia group received no extra interventions. Data were analyzed using repeated-measures ANOVA.
Results: In the normothermia group, there was no significant change in nasopharyngeal (-0.8 ± 0.6°C), intracerebral (-0.6 ± 0.8°C), or esophageal (-0.2 ± 0.6°C) temperatures during 20 minutes of resuscitation. However, in the hypothermia group, application of ice during resuscitation significantly reduced nasopharyngeal (-2.9 ± 1.4°C), intracerebral (-2.1 ± 0.6°C), and esophageal (-1.4 ± 0.8°C) temperatures.
Conclusions: External application of ice packs during resuscitation effectively reduced intracerebral temperatures in swine by an amount that improved neurologic outcomes in previous large animal studies. These data suggest that clinically significant cerebral cooling could be accomplished with a noninvasive, inexpensive, and universally available intervention. Further studies are required to assess the clinical feasibility and therapeutic efficacy of this intervention.     

Coronary artery bypass grafting bundled payment proposal will have significant financial impact on hospitals

Objectives

The Centers for Medicare and Medicaid Services plans to institute a 5-year trial of bundled payments for coronary artery bypass grafting through 90 days after discharge. To investigate the impact, we reviewed actual inpatient costs for patients undergoing bypass surgery relative to the target price.

Different methods of modelling intraoperative hypotension and their association with postoperative complications in patients undergoing non-cardiac surgery

Background

Associations between intraoperative hypotension (IOH) and postoperative complications have been reported. We examined whether using different methods to model IOH affected the association with postoperative myocardial injury (POMI) and acute kidney injury (AKI).

An Extraperitoneal Technique for Murine Heterotopic Cardiac Transplantation

The mouse heterotopic cardiac transplantation model has been used extensively by investigators in the field of organ transplantation to study the rejection process, test new antirejection treatments, tolerance induction protocols or to understand basic immunological principles. Due to its extensive use, any small refinement of the technique would have a major impact on replacement, reduction and refinement (commonly known as the 3Rs). Here, we describe a novel approach to refine this model. The donor aorta and pulmonary artery are anastomosed peripherally to the femoral artery and vein of the recipient, respectively. The technical success rate is comparable to the conventional abdominal site, but it avoids a laparotomy and handling of the bowels making it less invasive method. As a result, recipients recover faster and require less postoperative analgesia. It is a major refinement under one of the 3Rs and would represent an advance in animal welfare in scientific research.     

Cholestatic Liver Injury After Biliary Reconstruction Impairs Transplanted Islet Viability and Function

Islet autotransplantation following total pancreatectomy differs from allograft transplantation with respect to the requirement of biliary reconstruction. Although it is known that careful consideration should be given to postoperative cholestatic liver injury after biliary reconstruction, its direct effects on transplanted islets have not been completely elucidated. In this study, we developed a murine model of postoperative cholestatic liver injury after biliary reconstruction with islet autotransplantation that involved syngeneic intraportal islet transplantation into chemically induced diabetic mice and common bile duct ligation. We assessed the viability and function of the transplanted islets. The impaired viability of transplanted islets and increased blood glucose levels indicated restoration of the diabetic state after common bile duct ligation in this murine model. Furthermore, impaired islet viability and function occurred earlier in the transplanted islets than in the surrounding liver tissues, which was consistent with the faster and higher expression of oxidative stress markers in the transplanted islets. Transplanted islets may be more vulnerable to oxidative stress caused by cholestatic liver injury than the surrounding liver tissue. Therefore, patients should be intensively managed after total pancreatectomy with islet autotransplantation to preserve viability and function of the transplanted islets.     

Interference effects of choice on confidence: Quantum characteristics of evidence accumulation

Decision-making relies on a process of evidence accumulation which generates support for possible hypotheses. Models of this process derived from classical stochastic theories assume that information accumulates by moving across definite levels of evidence, carving out a single trajectory across these levels over time. In contrast, quantum decision models assume that evidence develops over time in a superposition state analogous to a wavelike pattern and that judgments and decisions are constructed by a measurement process by which a definite state of evidence is created from this indefinite state. This constructive process implies that interference effects should arise when multiple responses (measurements) are elicited over time. We report such an interference effect during a motion direction discrimination task. Decisions during the task interfered with subsequent confidence judgments, resulting in less extreme and more accurate judgments than when no decision was elicited. These results provide qualitative and quantitative support for a quantum random walk model of evidence accumulation over the popular Markov random walk model. We discuss the cognitive and neural implications of modeling evidence accumulation as a quantum dynamic system.Decisions in a wide range of tasks (e.g., inferring the presence or absence of a disease, the guilt or innocence of a suspect, and the left or right direction of enemy movement) require evidence to be accumulated in support of different hypotheses. Arguably, the most successful theory of evidence accumulation in humans and other animals is Markov random walk (MRW) theory (and diffusion models, their continuous space extensions) (1, 2). MRWs can be viewed as psychological implementations of a first-order Bayesian inference process that assigns a posterior probability to each hypothesis (3). MRWs can account for choices, response times, and confidence for a variety of different decision types (2, 4). Moreover, these models of the accumulation process have been connected to neural activity during decision-making (5, 6).According to MRW models, when deciding between two hypotheses, the cumulative evidence for or against each hypothesis realizes different levels at different times to generate a single particle-like trajectory of evidence levels across time (Fig. 1). At any point in time, the decision-maker has a definite level of evidence, and choices are made by comparing the existing level of evidence against a criterion. Evidence above the criterion favors one option, and evidence below it favors the alternative. Other responses are modeled in a similar manner; for example, confidence ratings are modeled by mapping evidence states onto one or more ratings (4). However, this idea that judgments and decisions are simply read out from the existing level of evidence—henceforth referred to as the “read-out” assumption—is inconsistent with the well-established idea that preferences and beliefs are constructed rather than revealed by judgments and decisions (7).Open in a separate windowFig. 1.Diagram of a state representation of a Markov and a quantum random walk model. In the Markov model, evidence (shaded state) evolves over time by moving from state to state, occupying one definite evidence level at any given time. In the quantum model the decision-maker is in an indefinite evidence state, with each evidence level having a probability amplitude (shadings) at each point in time.We present an alternative model of choice and judgment based on quantum random walk (QRW) theory (8–11), which posits that preferences and beliefs are constructed when a judgment or decision is made. Note that this work does not make the assumption that the brain is a quantum computer; instead, we simply use the mathematics of quantum theory to explain and predict human behavior. According to QRW theory, at any point in time before a decision, the decision-maker is in a superposition state that is not located at a single level of evidence. Instead, each level of evidence has a potential to be expressed, formalized as a probability amplitude (Fig. 1). New information changes the amplitudes, producing a wavelike process that moves the amplitude distribution across time.In some ways the QRW is like a second-order Bayesian model (12). According to the latter, the decision-maker assigns a probability (rather than an amplitude) to each level of evidence for each hypothesis. However, like the MRW model, second-order Bayesian models are perfectly compatible with the read-out assumption, and as an optimal model, this would suggest that a decision should not change the probability assigned to each evidence level. In contrast, a QRW, like all quantum models of cognition (13), treats a judgment or decision as a measurement process that constructs a definite state from an indefinite (superposition) state. When a decision is made, the indefinite state collapses onto a set of evidence levels that correspond to the observed choice, producing a definite choice state. Confidence ratings work similarly, with the indefinite state collapsing onto a more specific set of levels corresponding to the observed rating.These different theories of choice and judgment have strong implications for sequences of responses. Consider the situation when decision-makers have to make a choice (e.g., decide that hypothesis A or B is true) and later rate their confidence that a given (usually the chosen) hypothesis is true. According to the read-out assumption, a choice is reported on the basis of existing evidence that does not change the internal state of evidence itself. This applies to the MRW, a second-order Bayesian model, and many other accumulation models as well. Thus, after pooling across a person’s choices, the distribution of confidence ratings should be identical to conditions in which the person makes no choice at all. By contrast, the state of the system in a QRW is changed when a choice creates a definite state. Subsequent processing starts from the definite state, and the amplitudes spread out again. Thus, if information processing continues after the initial stage, the QRW predicts an interference effect where the marginal distribution of confidence judgments following a choice will differ from a condition in which no choice is made.A proof of the predicted interference effect for QRWs is in SI Appendix. The proof shows that the interference effect of choice on confidence is the result of the interaction between the creation of a definite state and subsequent evidence accumulation after making a choice. Subsequent or second-stage processing is a necessary condition for the effect. Critically, second-stage processing occurs when people are asked to report a confidence rating following a choice, giving rise to response reversals (14) and other properties (15). We also provide a proof that MRWs predict no difference between the marginal distributions of confidence ratings (i.e., no interference) regardless of the presence of second-stage processing. This proof holds for a large range of MRWs, including ones with decay (16), leakage of evidence (17), and trial-by-trial variability in the decision process (18).     

Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments

Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function was consistently observed in association with either hEPCR (n = 15), hTBM (n = 4), or hEPCR.hTFPI (n = 11), but the loss of vascular barrier function in the xenograft and systemic inflammation in the recipient typically occurred within 24 h. Co-expression of hEPCR and hTBM (n = 11) and additionally blocking multiple pro-inflammatory innate and adaptive immune mechanisms was more consistently associated with survival >1 day, with one recipient surviving for 31 days. Combining targeted genetic modifications to the lung xenograft with selective innate and adaptive immune suppression enables prolonged initial life-supporting lung function and extends lung xenograft recipient survival, and illustrates residual barriers and candidate treatment strategies that may enable the clinical application of other organ xenografts.