See one, simulate many, do one, teach one: cardiac surgical simulation.

PURPOSE OF REVIEW: To review the cardiac surgical simulation experience with a focus on data supporting its use. RECENT FINDINGS: Simulators have been used to improve trainee performance across multiple surgical domains. Few cardiac surgery residency programs have incorporated the use of simulation individually and Boot Camp programs in the United States and Canada have also introduced surgical simulation early in cardiac surgical training. Simulation curricula have some common elements: component tasks, deliberate practice, progressive operative responsibility, and coaching by an experienced surgeon. Cardiac surgical simulators can range from inexpensive, low-fidelity models for the practice of isolated skills to high-fidelity, operating room-scenarios. Multiple small studies have consistently demonstrated that the use of simulation improves qualitative and quantitative performance measures as well as overall resident confidence in clinical settings. To our knowledge, no study has demonstrated that use of simulation has led to improved quantitative performance measures in the operating room or patient outcomes. The barriers to wider use of surgical simulators include perceived lack of time and resources, the need for sustained practice and the lack of high-quality data to demonstrate clinical benefit. SUMMARY: Incorporation of cardiac surgery simulation has been slow in most residency programs. There is consistent data demonstrating that simulation improves resident performance measures of simulation-based tasks but whether this will lead to improved patient outcomes remains an open question.

Motor vehicle crashes during pregnancy and cerebral palsy during infancy: a longitudinal cohort analysis.

OBJECTIVES: To assess the incidence of cerebral palsy among children born to mothers who had their pregnancy complicated by a motor vehicle crash. DESIGN: Retrospective longitudinal cohort analysis of children born from 1 April 2002 to 31 March 2012 in Ontario, Canada. PARTICIPANTS: Cases defined as pregnancies complicated by a motor vehicle crash and controls as remaining pregnancies with no crash. MAIN OUTCOME: Subsequent diagnosis of cerebral palsy by age 3 years. RESULTS: A total of 1 325 660 newborns were analysed, of whom 7933 were involved in a motor vehicle crash during pregnancy. A total of 2328 were subsequently diagnosed with cerebral palsy, equal to an absolute risk of 1.8 per 1000 newborns. For the entire cohort, motor vehicle crashes correlated with a 29% increased risk of subsequent cerebral palsy that was not statistically significant (95% CI -16 to +110, p=0.274). The increased risk was only significant for those with preterm birth who showed an 89% increased risk of subsequent cerebral palsy associated with a motor vehicle crash (95% CI +7 to +266, p=0.037). No significant increase was apparent for those with a term delivery (95% CI -62 to +79, p=0.510). A propensity score-matched analysis of preterm births (n=4384) yielded a 138% increased relative risk of cerebral palsy associated with a motor vehicle crash (95% CI +27 to +349, p=0.007), equal to an absolute increase of about 10.9 additional cases per 1000 newborns (18.2 vs 7.3, p=0.010). CONCLUSIONS: Motor vehicle crashes during pregnancy may be associated with an increased risk of cerebral palsy among the subgroup of cases with preterm birth. The increase highlights a specific role for traffic safety advice in prenatal care.

Synapse formation changes the rules for desensitization of PKC translocation in Aplysia.

Protein kinase Cs (PKCs) are activated by translocating from the cytoplasm to the membrane. We have previously shown that serotonin-mediated translocation of PKC to the plasma membrane in Aplysia sensory neurons was subject to desensitization, a decrease in the ability of serotonin to induce translocation after previous application of serotonin. In Aplysia, changes in the strength of the sensory-motor neuron synapse are important for behavioral sensitization and PKC regulates a number of important aspects of this form of synaptic plasticity. We have previously suggested that the desensitization of PKC translocation in Aplysia sensory neurons may partially explain the differences between spaced and massed training, as spaced applications of serotonin, a cellular analog of spaced training, cause greater desensitization of PKC translocation than one massed application of serotonin, a cellular analog of massed training. Our previous studies were performed in isolated sensory neurons. In the present study, we monitored translocation of fluorescently-tagged PKC to the plasma membrane in living sensory neurons that were co-cultured with motor neurons to allow for synapse formation. We show that desensitization now becomes similar during spaced and massed applications of serotonin. We had previously modeled the signaling pathways that govern desensitization in isolated sensory neurons. We now modify this mathematical model to account for the changes observed in desensitization dynamics following synapse formation. Our study shows that synapse formation leads to significant changes in the molecular signaling networks that underlie desensitization of PKC translocation.

Tunable oscillations and chaotic dynamics in systems with localized synthesis.

Biological systems contain biochemical control networks that reside within a remarkable spatial structure. We present a theoretical study of a biological system in which two chemically coupled species, an activating species and an inhibiting species forming a negative feedback, are synthesized at unique sites and interact with each other through diffusion. The dynamical behaviors in these systems depend on the spatial locations of these synthetic sites. In a negative feedback system with two sites, we find two dynamical modes: fixed point and stable oscillations whose frequency can be tuned by varying the distance between the sites. When there are multiple synthetic sites, we find more diverse dynamics, including chaos, quasiperiodicity, and bistability. Based on this theoretical analysis, it should be possible to create in the laboratory synthetic circuits displaying these dynamics. This study illustrates the concept of "spatial switching," in which bifurcations in the dynamics occur as a function of the geometry of the system.

Molecular determinants of the spacing effect.

Long-term memory formation is sensitive to the pattern of training sessions. Training distributed over time (spaced training) is superior at generating long-term memories than training presented with little or no rest interval (massed training). This spacing effect was observed in a range of organisms from invertebrates to humans. In the present paper, we discuss the evidence supporting cyclic-AMP response element-binding protein 2 (CREB), a transcription factor, as being an important molecule mediating long-term memory formation after spaced training. We also review the main upstream proteins that regulate CREB in different model organisms. Those include the eukaryotic translation initiation factor (eIF2α), protein phosphatase I (PP1), mitogen-activated protein kinase (MAPK), and the protein tyrosine phosphatase corkscrew. Finally, we discuss PKC activation and protein synthesis and degradation as mechanisms by which neurons decode the spacing intervals.

The rates of protein synthesis and degradation account for the differential response of neurons to spaced and massed training protocols.

The sensory-motor neuron synapse of Aplysia is an excellent model system for investigating the biochemical changes underlying memory formation. In this system, training that is separated by rest periods (spaced training) leads to persistent changes in synaptic strength that depend on biochemical pathways that are different from those that occur when the training lacks rest periods (massed training). Recently, we have shown that in isolated sensory neurons, applications of serotonin, the neurotransmitter implicated in inducing these synaptic changes during memory formation, lead to desensitization of the PKC Apl II response, in a manner that depends on the method of application (spaced versus massed). Here, we develop a mathematical model of this response in order to gain insight into how neurons sense these different training protocols. The model was developed incrementally, and each component was experimentally validated, leading to two novel findings: First, the increased desensitization due to PKA-mediated heterologous desensitization is coupled to a faster recovery than the homologous desensitization that occurs in the absence of PKA activity. Second, the model suggests that increased spacing leads to greater desensitization due to the short half-life of a hypothetical protein, whose production prevents homologous desensitization. Thus, we predict that the effects of differential spacing are largely driven by the rates of production and degradation of proteins. This prediction suggests a powerful mechanism by which information about time is incorporated into neuronal processing.

Germ-line DNA copy number variation frequencies in a large North American population.

Genomic copy number variation (CNV) is a recently identified form of global genetic variation in the human genome. The Affymetrix GeneChip 100 and 500 K SNP genotyping platforms were used to perform a large-scale population-based study of CNV frequency. We constructed a genomic map of 578 CNV regions, covering approximately 220 Mb (7.3%) of the human genome, identifying 183 previously unknown intervals. Copy number changes were observed to occur infrequently (<1%) in the majority (>93%) of these genomic regions, but encompass hundreds of genes and disease loci. This North American population-based map will be a useful resource for future genetic studies.