Deep Hypothermic Circulatory Arrest Effectively Preserves Neurocognitive Function

Few (conflicting) studies have quantitatively assessed neurocognitive effects of deep hypothermic circulatory arrest (DHCA), and even fewer have looked at the long-term effects of DHCA. In this study, we aim to determine if DHCA negatively affects neurocognitive function and if so, are the effects long-term. We assess neurocognitive function quantitatively before and after DHCA and also in comparison with non-DHCA patients. 62 aortic surgical patients underwent a battery of neuropsychometric tests, both pre and post-operatively, evaluating multiple aspects of memory, processing speed, executive function, and global cognition. 33 patients did not require DHCA, and 29 underwent DHCA as the sole means of cerebral protection. Of these, 19 patients who tested positive for cognitive deficits, 8 of whom underwent DHCA and 11 who did not, were followed long-term with an additional testing months to years post-operatively. Neurocognitive deficit was defined as greater than 20% decline in two or more cognitive areas. Pre and post-operative test scores, as well as incidence of neurocognitive deficit , were compared within each group (post versus pre-operatively), and between the non-DHCA and DHCA groups. There were no significant differences in the post versus pre-operative scores in any cognitive area tested between DHCA and non-DHCA groups. There was also no difference between the two groups in incidence of neurocognitive deficit : 13 non-DHCA, 11 DHCA (p = 1.00). In addition, there was no correlation between time under DHCA and incidence of neurocognitive deficit . Within both groups, there was a mild decline in memory in the areas of acquisition, retention, and delayed recall. Within the DHCA group, recognition was also affected. Time under DHCA up to 40 minutes was also found to be safe neurocognitively. Of the 24 patients that who incurred a neurocognitive deficit, 19 participated in further follow-up, and of these, 4 DHCA and 2 non-DHCA patients had persistent memory deficits (p = 0.32). There was also no statistically significant difference in duration under DHCA between those who did or did not recover from their deficits (p = 0.56). DHCA patients who did have persistent memory deficits tended to have additional aspects of memory become affected when tested at further follow-up. There was a statistically significant difference in age, above or below 70 years old, between patients whose memory deficits persisted or recovered (p \u3c 0.001). While cardiac surgery had some effects on memory, overall neurocognitive function was well preserved and did not differ between DHCA and non-DHCA patients. DHCA does not affect whether or not memory deficits incurred post-operatively persist, but in those patients who underwent DHCA whose memory deficits did persist, those deficits tended to affect additional memory aspects that on previous testing had not been affected. What does affect the temporal nature of memory deficits is age, with patients over the age of 70 having a higher incidence of persistent long-term memory deficits. This study provides strong evidence that straight DHCA effectively preserves neurocognitive function

Frustration induced phases in migrating cell clusters

Collective motion of cells is common in many physiological processes, including tissue development, repair, and tumor formation. Recent experiments have shown that certain malignant cancer cells form clusters in a chemoattractant gradient, which display three different phases of motion: translational, rotational, and random. Intriguingly, all three phases are observed simultaneously, with clusters spontaneously switching between these modes of motion. The origin of this behavior is not understood at present, especially the robust appearance of cluster rotations. Guided by experiments on the motion of two-dimensional clusters in-vitro, we developed an agent based model in which the cells form a cohesive cluster due to attractive and alignment interactions but with potentially different behaviors based on their local environment. We find that when cells at the cluster rim are more motile, all three phases of motion coexist, in excellent agreement with the observations. Using the model we can identify that the transitions between different phases are driven by a competition between an ordered rim and a disordered core accompanied by the creation and annihilation of topological defects in the velocity field. The model makes definite predictions regarding the dependence of the motility phase of the cluster on its size and external chemical gradient, which agree with our experimental data. Our results suggest that heterogeneous behavior of individuals, based on local environment, can lead to novel, experimentally observed phases of collective motion.Comment: 14 pages, 5 figure

Silicon-based nanochannel glucose sensor

Silicon nanochannel biological field effect transistors have been developed for glucose detection. The device is nanofabricated from a silicon-on-insulator wafer with a top-down approach and surface functionalized with glucose oxidase. The differential conductance of silicon nanowires, tuned with source-drain bias voltage, is demonstrated to be sensitive to the biocatalyzed oxidation of glucose. The glucose biosensor response is linear in the 0.5-8 mM concentration range with 3-5 min response time. This silicon nanochannel-based glucose biosensor technology offers the possibility of high density, high quality glucose biosensor integration with silicon-based circuitry.Comment: 3 pages, 3 figures, two-column format. Related papers can be found at http://nano.bu.ed

Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain.

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management

Multivariate Modeling of Natural Gas Spot Trading Hubs Incorporating Futures Market Realized Volatility

Financial markets for Liquified Natural Gas (LNG) are an important and rapidly-growing segment of commodities markets. Like other commodities markets, there is an inherent spatial structure to LNG markets, with different price dynamics for different points of delivery hubs. Certain hubs support highly liquid markets, allowing efficient and robust price discovery, while others are highly illiquid, limiting the effectiveness of standard risk management techniques. We propose a joint modeling strategy, which uses high-frequency information from thickly-traded hubs to improve volatility estimation and risk management at thinly traded hubs. The resulting model has superior in- and out-of-sample predictive performance, particularly for several commonly used risk management metrics, demonstrating that joint modeling is indeed possible and useful. To improve estimation, a Bayesian estimation strategy is employed and data-driven weakly informative priors are suggested. Our model is robust to sparse data and can be effectively used in any market with similar irregular patterns of data availability

Research Synthesis for the California Zero Traffic Fatalities Task Force

This research synthesis consists of a set of white papers that jointly provide a review of research on the current practicefor setting speed limits and future opportunities to improve roadway safety. This synthesis was developed to inform thework of the Zero Traffic Fatalities Task Force, which was formed in 2019 by the California State Transportation Agencyin response to California Assembly Bill 2363 (Friedman). The statutory goal of the Task Force is to develop a structured,coordinated process for early engagement of all parties to develop policies to reduce traffic fatalities to zero. Thisreport addresses the following critical issues related to the work of the Task Force: (i) the relationship between trafficspeed and safety; (ii) lack of empirical justification for continuing to use the 85th percentile rule; (iii) why we need toreconsider current speed limit setting practices; (iv) promising alternatives to current methods of setting speed limits;and (v) improving road designs to increase road user safety

Holes in the walls: primordial black holes as a solution to the cosmological domain wall problem

We propose a scenario in which the cosmological domain wall and monopole problems are solved without any fine tuning of the initial conditions or parameters in the Lagrangian of an underlying filed theory. In this scenario domain walls sweep out (unwind) the monopoles from the early universe, then the fast primordial black holes perforate the domain walls, change their topology and destroy them. We find further that the (old vacuum) energy density released from the domain walls could alleviate but not solve the cosmological flatness problem.Comment: References added; Published in Phys. Rev.

Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala

Corticotropin-releasing factor receptor CRF1 has been implicated in the neurobiological mechanisms of anxiety and depression. The amygdala plays an important role in affective states and disorders such as anxiety and depression. The amygdala is also emerging as a neural substrate of pain affect. However, the involvement of the amygdala in the interaction of pain and anxiety remains to be determined. This study tested the hypothesis that CRF1 receptors in the amygdala are critically involved in pain-related anxiety. Anxiety-like behavior was determined in adult male rats using the elevated plus maze (EPM) test. The open-arm preference (ratio of open arm entries to the total number of entries) was measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal thresholds for noxious mechanical stimulation of the knee. Measurements were made in normal rats and in rats with arthritis induced in one knee by intraarticular injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914) or vehicle was administered systemically (i.p.) or into the central nucleus of the amygdala (CeA, by microdialysis). The arthritis group showed a decreased preference for the open arms in the EPM and decreased hindlimb withdrawal thresholds. Systemic or intraamygdalar (into the CeA) administration of NBI27914, but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses, nearly reversing the arthritis pain-related changes. This study shows for the first time that CRF1 receptors in the amygdala contribute critically to pain-related anxiety-like behavior and nocifensive responses in a model of arthritic pain. The results are a direct demonstration that the clinically well-documented relationship between pain and anxiety involves the amygdala