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1.
Juan D. Gonzalez‐Sanz 《Nursing philosophy》2020,21(4)
The current situation in which the humanities are disparaged affects all university disciplines, including nursing, in whose historical evolution the humanities have always been present in one form or another. Looking beyond this disrepute, this study proposes that nursing renew its attention to classical philosophy. Specifically, it invites a close reading of Xenophon's Anabasis and Plato's Meno, to get three related goals: to show how the use of ancient texts are very valuable tools for the philosophical initiation of nursing students and can help them reflect on their choice of nursing as a practical activity; to reflect on the problem of virtue and the nature of the good life; and to show how the interaction with ancient texts allows students to reflect on questions and issues of life, theirs and others, that are not open to investigation through a purely scientific method. Consequently, both Anabasis and Meno readings strengthen the intellectual relationship between philosophy and nursing, enabling the latter to delve deeper into the key questions of its own thought as a discipline. 相似文献
2.
N. S. Hari Narayana Moorthy Sergio F. Sousa Maria J. Ramos Pedro A. Fernandes 《Medicinal chemistry research》2016,25(7):1340-1357
Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets. 相似文献
3.
Khaled Adil Marija Popovic Fabio L. Cury Sergio L. Faria Marie Duclos Luis Souhami 《Practical radiation oncology》2019,9(1):24-28
Purpose
This study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss.Methods and materials
The study included patients with bladder cancer who were treated with a hypofractionated course of radiation therapy delivered with intensity modulated radiation therapy. The clinical target volume (CTV) was the whole empty bladder, and the PTV consisted of a 1.5-cm margin around the bladder (PTV1.5 cm). Patients underwent daily CBCT imaging before treatment to assess the bladder volume and ensure accurate positioning. We investigated 2 additional smaller PTV margin expansions to determine the most appropriate volume to be used with CBCT as a daily image guided radiation therapy modality. These margins were created retrospectively on every CBCT. The first additional volume was a uniform PTV margin of the surrounding 1 cm (PTV1 cm). When considering that the majority of the internal bladder movement was due to the variation in filling that occurs in the superior and anterior directions, a second volume of an anisotropic PTV margin with a 1.5-cm superior/anterior and 1 cm in other directions (PTV1/1.5 cm) was created. We recorded the frequency and measured the volume of bladder falling out of each PTV based on the daily CBCT.Results
For the purpose of this study, we considered an arbitrary 5 cm3 of CTV falling out of the designated PTV as a clinically significant volumetric miss. The frequency of such a miss when applying the uniform PTV1 cm was 1%. However, when applying the uniform PTV1.5 cm and anisotropic PTV1/1.5 cm margins, the frequency was 0.5% and 0.5%, respectively.Conclusions
The anisotropic PTV expansion of 1.5 cm superiorly and anteriorly and 1 cm in all other directions around the bladder (CTV) provides a safe PTV approach when daily CBCT imaging is used to localize an empty bladder. 相似文献4.
5.
Julia Thornton Snider Jesse Sussell Mahlet Gizaw Tebeka Alicia Gonzalez Joshua T. Cohen Peter Neumann 《Value in health》2019,22(3):332-339
Background
Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact.Objective
We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER).Study Design
Retrospective analysis of pharmaceutical sales data.Methods
From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed “unmanaged uptake,” and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market).Results
Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The “unmanaged uptake” assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data.Conclusions
This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results. 相似文献6.
Toshiro Hara Rony Chanoch-Myers Nathan D. Mathewson Chad Myskiw Lyla Atta Lillian Bussema Stephen W. Eichhorn Alissa C. Greenwald Gabriela S. Kinker Christopher Rodman L. Nicolas Gonzalez Castro Hiroaki Wakimoto Orit Rozenblatt-Rosen Xiaowei Zhuang Jean Fan Tony Hunter Inder M. Verma Kai W. Wucherpfennig Itay Tirosh 《Cancer cell》2021,39(6):779-792.e11
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10.
Marlen Z. Gonzalez Lane Beckes Joanna Chango Joseph P. Allen James A. Coan 《Social cognitive and affective neuroscience》2015,10(7):921-928
Neuroimaging studies using the social-exclusion paradigm Cyberball indicate increased dorsal anterior cingulate cortex (dACC) and right insula activity as a function of exclusion. However, comparatively less work has been done on how social status factors may moderate this finding. This study used the Cyberball paradigm with 85 (45 females) socio-economically diverse participants from a larger longitudinal sample. We tested whether neighborhood quality during adolescence would predict subsequent neural responding to social exclusion in young adulthood. Given previous behavioral studies indicating greater social vigilance and negative evaluation as a function of lower status, we expected that lower adolescent neighborhood quality would predict greater dACC activity during exclusion at young adulthood. Our findings indicate that young adults who lived in low-quality neighborhoods in adolescence showed greater dACC activity to social exclusion than those who lived in higher quality neighborhoods. Lower neighborhood quality also predicted greater prefrontal activation in the superior frontal gyrus, dorsal medial prefrontal cortex and the middle frontal gyrus, possibly indicating greater regulatory effort. Finally, this effect was not driven by subsequent ratings of distress during exclusion. In sum, adolescent neighborhood quality appears to potentiate neural responses to social exclusion in young adulthood, effects that are independent of felt distress. 相似文献