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Inertial measurement units and normative values enable clinicians to quantify clinical walking tests and set rehabilitation goals. Objectives of this study were (1) to compare time- and distance-based walking tests in individuals with lower limb amputation (iLLA) and normative values following rehabilitation discharge (T1) and 6 weeks after discharge (T2) and (2) to investigate spatiotemporal and foot kinematic parameters over a 6-minute walk test using inertial measurement units. Twelve iLLA participated in this study. Distance, cadence, stance ratio, loading rate ratio, push-up ratio, path length, and minimum toe clearance were analyzed during 6-minute walk test. Nonparametric repeated-measures analysis of variance tests, Bonferroni corrections, were performed. Time of distance-based walking tests diminished at T2 (P < .02). Compared with normative values, walking performance in iLLA was reduced. Cadence at T2 increased significantly (P = .026). Stance ratio increased in both legs at T2 (P < .05). Push-up ratio tended to decrease at T2 in the amputated leg (P = .0003). Variability of path length and minimum toe clearance at T2 were less than at T1 in the nonamputated leg (P < .05). Spatiotemporal improvement at T2 could be due to prosthesis adaptation in iLLA. The lower performance of the functional walk test compared with normative values could be due to amputation and pain-related fatigue.

Background: A recent amputation leads to decreased functional capacities in the lower limb amputees (LLA), especially during walking. Assessments of LLA's gait in clinical settings are used to provide feedback on their evolution without quantifying gait parameters distinctly, unlike new technologies, such as inertial sensors (IMUs), which have demonstrated their effectiveness in different environments and populations., Research Question: How do the spatial-temporal gait parameters and kinematics of the LLA evolve quantitatively over a six-minute walk test (6MWT) and is the use of inertial sensors relevant in clinical practice to quantify those parameters?, Methods: Fifteen LLA from a study cohort performed a 6MWT post-rehabilitation, wearing inertial sensors on both feet to provide gait parameters (i.e., minimum toe clearance (minTC), speed, cadence, stance time and foot flat ratio (FFr)) over this test. A non-parametric ANOVA was conducted comparing the evolution of each parameter over the 6MWT (12 intervals of 30 s). Significance level was set at P ≤  0.05. Post-hoc Wilcoxon signed-rank tests were performed if a main effect was detected., Results: MinTC and stance phase variability along the 6MWT were significantly different over time. Cadence variability and speed variation were significantly different between both feet (amputated and non-amputated leg)., Significance: The increased variability in gait parameters along the 6MWT suggests a greater risk of future mobility problems following a return in community. The data provided by the IMUs reflect the potential of the clinical rehabilitation programme and could, therefore, help clinicians to refine their interventions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: The purpose of this evidence-based management practice project was to analyse dimensions of the Getting my Work Done issue, the only one of seven issues of highest concern for which 907 nurse interviewees were unable to identify effective strategies, formulate a 'best management practice', integrate the practice into clinical settings and evaluate results. METHOD/PROCESS: The evidence-based management practice process was used to identify the major impediment to Getting Work Done-assignment to multiple patients with simultaneous complex needs. Best management practice consisted of class presentation of a clinical-management problem scenario to 144 residents in nine Magnet hospitals, a private action commitment, class discussion and terminal action commitments., Results: Responses indicated that this 'best management practice' was effective in helping newly licensed registered nurses manage and handle multiple patients with simultaneous complex needs. A major avenue of resolution was perception of professional practice responsibilities as a series of complex, interrelated, adaptive systems. CONCLUSIONS/IMPLICATIONS FOR NURSING MANAGEMENT: Perception and use of the principles of complexity science assists newly licensed registered nurses in mastering management dilemmas that inhibit professional practice. In many participating hospitals, plans are underway to expand this best practice to include input and perception exchange among experienced nurses, managers and physicians., (© 2013 Blackwell Publishing Ltd.)

Ovarian cancer is the leading cause of death from gynecologic cancer. Improvement in the clinical outcome of patients is likely to be achieved by the identification of molecular events that underlie the oncogenesis of ovarian cancer. Here we show that the anaplastic lymphoma kinase (ALK) is aberrantly activated in ovarian cancer. Using an unbiased and global phosphoproteomic approach, we profiled 69 Chinese primary ovarian tumor tissues and found ALK to be aberrantly expressed and phosphorylated in 4 tumors. Genetic characterization of these ALK-positive tumors indicated that full-length ALK expression in two serous carcinoma patients is consistent with ALK gene copy number gain, whereas a stromal sarcoma patient carries a novel transmembrane ALK fusion gene: FN1-ALK. Biochemical and functional analysis showed that both full-length ALK and FN1-ALK are oncogenic, and tumors expressing ALK or FN1-ALK are sensitive to ALK kinase inhibitors. Furthermore, immunohistochemical analysis of ovarian tumor tissue microarray detected aberrant ALK expression in 2% to 4% serous carcinoma patients. Our findings provide new insights into the pathogenesis of ovarian cancer and identify ALK as a potential therapeutic target in a subset of serous ovarian carcinoma and stromal sarcoma patients., (©2012 AACR.)

Activating mutations of FMS-like tyrosine kinase-3 (FLT3) are found in approximately 30% of patients with acute myeloid leukemia (AML). FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3) and B cell acute lymphoblastic leukemia (normal and amplification of FLT3) cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC), we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr) that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia.

Elevated coexpression of colony-stimulating factor receptor (CSF-1R) and its ligand, CSF-1, correlates with invasiveness and poor prognosis of a variety of epithelial tumors (Kacinski, B.M. 1995. Ann. Med. 27:79-85). Apart from recruitment of macrophages to the tumor site, the mechanisms by which CSF-1 may potentiate invasion are poorly understood. We show that autocrine CSF-1R activation induces hyperproliferation and a profound, progressive disruption of junctional integrity in acinar structures formed by human mammary epithelial cells in three-dimensional culture. Acini coexpressing receptor and ligand exhibit a dramatic relocalization of E-cadherin from the plasma membrane to punctate intracellular vesicles, accompanied by its loss from the Triton-insoluble fraction. Interfering with Src kinase activity, either by pharmacological inhibition or mutation of the Y561 docking site on CSF-1R, prevents E-cadherin translocation, suggesting that CSF-1R disrupts cell adhesion by uncoupling adherens junction complexes from the cytoskeleton and promoting cadherin internalization through a Src-dependent mechanism. These findings provide a mechanistic basis whereby CSF-1R could contribute to invasive progression in epithelial cancers.