305 research outputs found

    Surgical Training and Education in Promoting Professionalism: a comparative assessment of virtue-based leadership development in otolaryngology-head and neck surgery residents

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    Introduction: Surgical Training and Education in Promoting Professionalism (STEPP) was developed in 2011 to train tomorrow's leaders during residency. It is based on virtue ethics and takes an approach similar to West Point military academy. The purpose of this research was: (i) to compare the virtue profiles of our residents with that of the military cohort using a standardized virtue assessment tool; and (ii) to assess the value of virtue education on residents. Methods: As part of STEPP, otolaryngology residents participated in a virtue-based validated assessment tool called Virtue in Action (VIA) Inventory. This was completed at the initiation of STEPP in July 2011 as well as 1 year later in June 2012. Comparison of the VIA to a military cohort was performed. Leadership ‘Basic Training’ is a series of forums focused on virtues of initiative, integrity, responsibility, self-discipline, and accountability. A pre- and post-test was administered assessing resident perceptions of the value of this ‘Basic Training’. Results: Virtues are shared between otolaryngology residents (n=9) and military personnel (n=2,433) as there were no significant differences in strength scores between two military comparison groups and otolaryngology-head and neck surgery (OHNS) residents. There was a significant improvement (p<0.001) in the understanding of components of the leadership vision and a significant improvement in the understanding of key leadership concepts based on ‘Basic Training’. All residents responded in the post-test that the STEPP program was valuable, up from 56%. Conclusions: A virtue-based approach is valued by residents as a part of leadership training during residency

    Propagation of an Earth-directed coronal mass ejection in three dimensions

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    Solar coronal mass ejections (CMEs) are the most significant drivers of adverse space weather at Earth, but the physics governing their propagation through the heliosphere is not well understood. While stereoscopic imaging of CMEs with the Solar Terrestrial Relations Observatory (STEREO) has provided some insight into their three-dimensional (3D) propagation, the mechanisms governing their evolution remain unclear due to difficulties in reconstructing their true 3D structure. Here we use a new elliptical tie-pointing technique to reconstruct a full CME front in 3D, enabling us to quantify its deflected trajectory from high latitudes along the ecliptic, and measure its increasing angular width and propagation from 2-46 solar radii (approximately 0.2 AU). Beyond 7 solar radii, we show that its motion is determined by an aerodynamic drag in the solar wind and, using our reconstruction as input for a 3D magnetohydrodynamic simulation, we determine an accurate arrival time at the Lagrangian L1 point near Earth.Comment: 5 figures, 2 supplementary movie

    Inducible Caspase9-mediated suicide gene for MSC-based cancer gene therapy

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    Cellular therapies based on mesenchymal stromal/stem cells (MSC) are promising strategies in regenerative medicine and oncology. Despite encouraging results, there is still some level of concerns on inoculating MSC in cancer patients. To face this issue, one possibility resides in engineering MSC by incorporating a suicide gene in order to control their fate once infused. Strategies based on Herpes Simplex Virus Thymidine Kinase (HSV-TK) and the Cytosine Deaminase genes have been developed and more recently a novel suicide gene, namely, iCasp9, has been proposed. This approach is based on a variant of human Caspase9 that binds with high affinity to a synthetic, bioinert small molecule (AP20187) leading to cell death. Based on this technology so far marginally applied to MSC, we tested the suitability of iCasp9 suicide strategy in MSC to further increase their safety. MSC have been transfected by a lentiviral vector carrying iCasp9 gene and then tested for viability after AP20187 treatment in comparison with mock-transfected cells. Moreover, accounting our anti-tumor approaches based on MSC expressing potent anti-cancer ligand TNF-Related Apoptosis-Inducing Ligand (TRAIL), we generated adipose MSC co-expressing iCasp9 and TRAIL successfully targeting an aggressive sarcoma type. These data show that anti-cancer and suicide mechanisms can coexist without affecting cells performance and hampering the tumoricidal activity mediated by TRAIL. In conclusion, this study originally indicates the suitability of combining a MSC-based anti-cancer gene approach with iCasp9 demonstrating efficiency and specificity

    Neural Substrates for the Motivational Regulation of Motor Recovery after Spinal-Cord Injury

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    It is believed that depression impedes and motivation enhances functional recovery after neuronal damage such as spinal-cord injury and stroke. However, the neuronal substrate underlying such psychological effects on functional recovery remains unclear. A longitudinal study of brain activation in the non-human primate model of partial spinal-cord injury using positron emission tomography (PET) revealed a contribution of the primary motor cortex (M1) to the recovery of finger dexterity through the rehabilitative training. Here, we show that activity of the ventral striatum, including the nucleus accumbens (NAc), which plays a critical role in processing of motivation, increased and its functional connectivity with M1 emerged and was progressively strengthened during the recovery. In addition, functional connectivities among M1, the ventral striatum and other structures belonging to neural circuits for processing motivation, such as the orbitofrontal cortex, anterior cingulate cortex and pedunculopontine tegmental nucleus were also strengthened during the recovery. These results give clues to the neuronal substrate for motivational regulation of motor learning required for functional recovery after spinal-cord injury

    A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation

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    Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviours and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes
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