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To improve the effectiveness of external stakeholder risks (ESRs) management in project portfolios (PPs), a portfolio-wide risk response approach is required. However, current research is inadequate to effectively identify response strategies for ESRs, which brings challenges to managing ESRs in PPs. In this context, the purpose of this study is to select an appropriate combination of response strategies for ESRs by considering interactions among ESRs, projects, and response strategies in the PP. A Bayesian influence diagram (BID) coupled with a multi-objective optimization model is deemed suitable for this context. Firstly, a probability-sensitivity matrix is established to determine the key ESRs. Then, a BID is constructed to calculate the expected values of different combinations of response strategies. Finally, integrating stakeholder satisfaction and strategy cost, an optimization model for risk response strategy selection is established to obtain candidate combinations. By combining expected values and candidate combinations, the optimal strategy combination is selected. The proposed model comprehensively considers and evaluates the interactions between risks, projects, and risk responses. This enhances the desirability of expected outcomes and reduces project execution costs.
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Fe3Al is a good magnetic loss absorber for microwave absorption. However, due to the relatively high density and poor impedance matching ratio, the potential of Fe3Al cannot be fully released. Herein, a dielectric loss absorber of carbon nanotubes (CNTs) is coupled with Fe3Al to form Fe3Al/CNTs composite absorbers. CNTs are randomly tangled and coated on the surface of the Fe3Al flakes, forming a connecting conductive network. By carefully tuning the content of CNTs, the optimized Fe3Al/CNTs composite absorber with 1.5% of CNTs can combine both magnetic loss and dielectric loss mechanisms, thus achieving an impedance matching ratio close to 1 while keeping strong attenuation for enhanced microwave absorption. As a result, an effective absorption bandwidth (RL ≤ -10 dB) of 4.73 GHz at a thickness of 2 mm is achieved.
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OBJECTIVE: To explore the clinical outcomes and establish a predictive model of hypoglycemia during colonoscopy preparation for diabetic patients. METHODS: Three-hundred ninety-four patients with diabetes who received colonoscopy were retrospectively enrolled in this study and assigned to hypoglycemia or non-hypoglycemia groups. Information about clinical characteristics and outcomes during colonoscopy preparation was collected and compared between the two groups. Logistic regression analysis was applied to identify the risk factors of hypoglycemia. These risk factors were used to construct a hypoglycemia predictive model verified by the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow goodness fit test. RESULTS: Among 394 participants, 66 (16.8%) underwent a total of 88 hypoglycemia attacks during the bowel preparation. Grade 1 hypoglycemia (≤3.9 mmol/L) comprised 90.9% (80/88) of all hypoglycemia attacks and grade 2 hypoglycemia accounted for 9.1% (8/88), signifying that grade 1 hypoglycemia is the most common type. No severe hypoglycemia was identified. The incidence of nocturnal hypoglycemia was 15.9%. Logistic regression analyses revealed that the main risk factors of hypoglycemia during colonoscopy preparation were postprandial C-peptide, serum triglyceride, gender, type of diabetes mellitus, and insulin injection frequencies. The area under the ROC curve of the hypoglycemia prediction model was 0.777 (95% CI: 0.720-0.833). CONCLUSION: Diabetic patients are prone to develop mild to moderate hypoglycemia during colonoscopy preparation. This study proposes a predictive model that could provide a reference for identifying patients with a high risk of hypoglycemia during colonoscopy preparation.
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Diabetes Mellitus , Hipoglucemia , Humanos , Estudios Retrospectivos , Hipoglucemia/diagnóstico , Hipoglucemia/epidemiología , Hipoglucemia/etiología , Factores de Riesgo , Colonoscopía/efectos adversosRESUMEN
BACKGROUND: The efficacy of endoscopic therapy on the long-term survival outcomes of T1b oesophageal cancer (EC) is unclear, this study was designed to clarify the survival outcomes of endoscopic therapy and to construct a model for predicting the prognosis in T1b EC patients. METHODS: This study was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017 of patients with T1bN0M0 EC. Cancer-specific survival (CSS) and overall survival (OS) were compared between endoscopic therapy group, esophagectomy group and chemoradiotherapy group, respectively. Stabilized inverse probability treatment weighting was used as the main analysis method. The propensity score matching method and an independent dataset from our hospital were used as sensitivity analysis. The least absolute shrinkage and selection operator regression (Lasso) was employed to sift variables. A prognostic model was then established and was verified in two external validation cohorts. RESULTS: The unadjusted 5-year CSS was 69.5% (95% CI, 61.5-77.5) for endoscopic therapy, 75.0% (95% CI, 71.5-78.5) for esophagectomy and 42.4% (95% CI, 31.0-53.8) for chemoradiotherapy. After stabilized inverse probability treatment weighting adjustment, CSS and OS were similar in endoscopic therapy and esophagectomy groups ( P =0.32, P =0.83), while the CSS and OS of chemoradiotherapy patients were inferior to endoscopic therapy patients ( P <0.01, P <0.01). Age, histology, grade, tumour size, and treatment were selected to build the prediction model. The area under the curve of receiver operating characteristics of 1, 3, and 5 years in the validation cohort 1 were 0.631, 0.618, 0.638, and 0.733, 0.683, 0.768 in the validation cohort 2. The calibration plots also demonstrated the consistency of predicted and actual values in the two external validation cohorts. CONCLUSION: Endoscopic therapy achieved comparable long-term survival outcomes to esophagectomy for T1b EC patients. The prediction model developed performed well in calculating the OS of patients with T1b EC.
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Neoplasias Esofágicas , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Pronóstico , Neoplasias Esofágicas/cirugía , Puntaje de Propensión , Programa de VERF , NomogramasRESUMEN
Fe-Al-Cr coatings with different content of Cr additive were prepared on 1045 carbon steel substrates by a laser cladding process. The incorporation of Cr atoms can effectively enhance the corrosion resistance of the coatings. In particular, the Fe-28Al-5Cr laser cladding coating exhibits the best film quality without phase segregation. In addition, the interfacial adhesion between the Fe-28Al-5Cr coating and the 1045 carbon steel substrate is improved. As a result, the Fe-28Al-5Cr laser cladding coating exhibits the best corrosion resistance in a 3.5 wt% NaCl solution under both immersion and electrochemical conditions. However, excessive Cr additive lead to the formation of Al8Cr5 in the grain boundaries, resulting in inferior corrosion resistance. Therefore, the new findings demonstrated in this work may inspire the design of high-quality coatings with excellent corrosion resistance.
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Microinvasive breast cancer (MBC for short) is a rare entity with the decision of axillary surgery under debate in clinical practice. We aimed to unravel the lymph node metastasis (LNM) rate, axillary surgery, and prognosis of MBC based on 11,692 patients derived from the Surveillance Epidemiology and End Results (SEER) database between 2003 and 2015. In this retrospective study, 19.5% (2276/11,692) of patients received axillary lymph node dissection (ALND), 80.5% (9416/11,692) received non-ALND. In the total cohort, 10-year breast cancer-specific survival (BCSS) was 96.3%, and the LNM rate was 6.4% (754/11,692). Multivariate analyses showed that LNM had the strongest predictive weight (N3, HR 14.200, 95% CI 7.933−25.417; N2, HR 12.945, 95% CI 7.725−21.694; N1, HR 3.05, 95% CI 2.246−4.140, all p < 0.001). Kaplan−Meier analyses showed that ALND did not confer a survival benefit on 10-year BCS in patients with N0 (94.7% vs. 97.1%, p < 0.001) and in patients with 1−2 positive nodes (92.1% vs. 89.5%, p = 0.355), respectively, when compared to non-ALND. Our study demonstrated that the vast majority of MBC have a low LNM rate and excellent prognosis; patients with LNM showed poor prognosis. Assessment of lymph node status is necessary, and non-ALND surgery is required and sufficient for MBC with 0−2 positive nodes.
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To obtain Fe3Al@Al2O3 core-shell absorbents, DO3-type Fe3Al powder was thermal treated in an argon atmosphere containing a trace amount of oxygen at different temperatures. Since Al atoms have a higher diffusion rate than that of the Fe atoms, Al atoms can migrate to the surface of the Fe3Al particle and in-situ convert to Al2O3 nanoparticles during the thermal treatment process. With the increase of the thermal treatment temperature, the Al2O3 nanoparticles grow larger, exhibiting different microwave absorption properties. In particular, the Fe3Al@Al2O3 obtained by controllable oxidation at 800 â exhibits the best microwave absorption properties, with the minimum reflection loss of -34 dB at 11.5 GHz when the thickness is 2 mm, and the bandwidth below -10 dB is as broad as 6.7 GHz. Since a dielectric Al2O3 shell with a proper thickness can increase the impedance matching ratio of the Fe3Al absorbent, more electromagnetic waves can come into the absorbent. In addition, the magnetic Fe3Al core can efficiently attenuate the absorbed electromagnetic waves by dimensional resonance and natural resonance.
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This paper firstly proposes a modified human factor classification analysis system (HFACS) framework based on literature analysis and the characteristics of falling accidents in construction. Second, a Bayesian network (BN) topology is constructed based on the dependence between human factors and organizational factors, and the probability distribution of the human-organizational factors in a BN risk assessment model is calculated based on falling accident reports and fuzzy set theory. Finally, the sensitivity of the causal factors is determined. The results show that 1) the most important reason for falling accidents is unsafe on-site supervision. 2) There are significant factors that influence falling accidents at different levels in the proposed model, including operation violations in the unsafe acts layer, factors related to an adverse technological environment for the unsafe acts layer, loopholes in site management in the unsafe on-site supervision layer, lack of safety culture in the adverse organizational influence layer, and lax government regulation in the adverse external environment layer. 3) According to the results of the BN risk assessment model, the most likely causes are loopholes in site management work, lack of safety culture, insufficient safety inspections and acceptance, vulnerable process management and operation violations.
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Accidentes por Caídas , Accidentes de Trabajo , Teorema de Bayes , Análisis Factorial , Humanos , ProbabilidadRESUMEN
Metastasis via lymphatic vessels or blood vessels is the leading cause of death for breast cancer, and lymphangiogenesis and angiogenesis are critical prerequisites for the tumor invasion-metastasis cascade. The research progress for tumor lymphangiogenesis has tended to lag behind that for angiogenesis due to the lack of specific markers. With the discovery of lymphatic endothelial cell (LEC) markers, growing evidence demonstrates that the LEC plays an active role in lymphatic formation and remodeling, tumor cell growth, invasion and intravasation, tumor-microenvironment remodeling, and antitumor immunity. However, some studies have drawn controversial conclusions due to the variation in the LEC markers and lymphangiogenesis assessments used. In this study, we review recent findings on tumor lymphangiogenesis, the most commonly used LEC markers, and parameters for lymphangiogenesis assessments, such as the lymphatic vessel density and lymphatic vessel invasion in human breast cancer. An in-depth understanding of tumor lymphangiogenesis and LEC markers can help to illustrate the mechanisms and distinct roles of lymphangiogenesis in breast cancer progression, which will help in exploring novel potential predictive biomarkers and therapeutic targets for breast cancer.
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In this research, a facile in-situ growth method was applied to load ZnFe2O4 nanoparticles on carbonyl iron (Fe) flakes. These loaded ZnFe2O4 exhibited cone shape with an average size of â¼200â¯nm. The results revealed that the frequency region with reflection loss <-10â¯dB (fE) was up to 6.2â¯GHz (dâ¯=â¯1.5â¯mm), suggesting excellent wideband electromagnetic absorption (EM) properties. The electromagnetic absorption mechanism was discussed in depth which attributed to the synergetic effect of Fe and ZnFe2O4. The loaded ZnFe2O4 played a key role on suppressing inverse electromagnetic radiation, eddy effect, simultaneous maintaining moderate magnetic loss ability. Besides, the formed interface of ZnFe2O4/Fe could induce interface polarization relaxation effect at external electromagnetic field, which greatly boosted the effective dielectric loss ability (ε''E). Meanwhile, the interface polarization intensity was controllable by tuning the weight ratio of Fe.
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Endogenous type I IFN production after innate immune recognition of tumor cells is critical for generating natural adaptive immune responses against tumors in vivo. We recently have reported that targeting low doses of IFN-ß to the tumor microenvironment using tumor-specific mAbs can facilitate antitumor immunity, which could be augmented further with PD-L1/PD-1 blockade. However, sustained high doses of type I IFNs in the tumor microenvironment, which are potently therapeutic alone, may function through distinct mechanisms. In the current report, we demonstrate that high-dose intratumoral type I IFNs indeed exerted a profound therapeutic effect in the murine B16 model, which unexpectedly did not increase T cell responses. Moreover, bone marrow chimeras revealed a role for type I IFN signaling on nonhematopoietic cells, and most of the therapeutic effect was retained in mice deficient in T, B, and NK cells. Rather, the tumor vasculature was ablated with high-dose intratumoral IFN-ß, and conditional deletion of IFN-α/ßR in Tie2-positive vascular endothelial cells eliminated most of the antitumor activity. Therefore, the major component of the antitumor activity of sustained high doses of type I IFNs occurs through a direct antiangiogenic effect. Our data help resolve conditions under which distinct antitumor mechanisms of type I IFNs are operational in vivo.
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Inhibidores de la Angiogénesis/administración & dosificación , Antineoplásicos/administración & dosificación , Interferón beta/administración & dosificación , Melanoma Experimental/irrigación sanguínea , Melanoma Experimental/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Receptor de Interferón alfa y beta/genética , Animales , Anticuerpos Monoclonales/inmunología , Linfocitos B/inmunología , Antígeno B7-H1/antagonistas & inhibidores , Línea Celular Tumoral , Células Asesinas Naturales/inmunología , Depleción Linfocítica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Linfocitos T/inmunología , Microambiente Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that is activated when cells experience energy deficiency and conversely suppressed in surfeit of energy supply. AMPK activation improves insulin sensitivity via multiple mechanisms, among which AMPK suppresses mTOR/S6K-mediated negative feedback regulation of insulin signaling. RESULTS: In the present study we further investigated the mechanism of AMPK-regulated insulin signaling. Our results showed that 5-aminoimidazole-4-carboxamide-1 ribonucleoside (AICAR) greatly enhanced the ability of insulin to stimulate the insulin receptor substrate-1 (IRS1)-associated PI3K activity in differentiated 3T3-F442a adipocytes, leading to increased Akt phosphorylation at S473, whereas insulin-stimulated activation of mTOR was diminished. In 3T3-F442a preadipocytes, these effects were attenuated by expression of a dominant negative mutant of AMPK alpha1 subunit. The enhancing effect of ACIAR on Akt phosphorylation was also observed when the cells were treated with EGF, suggesting that it is regulated at a step beyond IR/IRS1. Indeed, when the cells were chronically treated with AICAR in the absence of insulin, Akt phosphorylation was progressively increased. This event was associated with an increase in levels of phosphatidylinositol -3,4,5-trisphosphate (PIP3) and blocked by Wortmannin. We then expressed the dominant negative mutant of PTEN (C124S) and found that the inhibition of endogenous PTEN per se did not affect phosphorylation of Akt at basal levels or upon treatment with AICAR or insulin. Thus, this result suggests that AMPK activation of Akt is not mediated by regulating phosphatase and tensin homologue (PTEN). CONCLUSION: Our present study demonstrates that AMPK exerts dual effects on the PI3K pathway, stimulating PI3K/Akt and inhibiting mTOR/S6K.
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Raf kinases are essential for regulating cell proliferation, survival, and tumorigenesis. However, the mechanisms by which Raf is activated are still incompletely understood. Phosphorylation plays a critical role in Raf activation in response to mitogens. The present study characterizes phosphorylation of Ser338, a crucial event for Raf-1 activation. Here we report that mutation of Lys375 to Met diminishes phosphorylation of Ser338 on both wild type Raf-1 in cells treated with epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA) and a constitutively active mutant in which Tyr340/Tyr341 are replaced by 2 aspartic acids, a conserved substitution present in natural B-Raf. The loss of Ser338 phosphorylation in these Raf mutants is not engendered by a mutation-induced conformational change, inasmuch as mutation of another site (Ser471 to Ala) in the activation segment also abolishes Ser338 phosphorylation, whereas both the kinase-dead mutants of Raf-1 are phosphorylated well by active Pak1. Furthermore, our data demonstrate that EGF-stimulated phosphorylation of Ser338 is inhibited by Sorafenib, a Raf kinase inhibitor, but not by the MEK inhibitor U0126. Interestingly, a kinase-dead mutation and Sorafenib also markedly reduce phosphorylation of Ser445 on B-Raf, a site equivalent to Raf-1 Ser338. Finally, our data reveal that Ser338 is phosphorylated on inactive Raf-1 by an active mutant of Raf-1 when they are dimerized in cells and that artificial dimerization of Raf-1 causes Ser338 phosphorylation, accompanied by activation of ERK1/2. Altogether, our data suggest that Ser338 on Raf-1 is autophosphorylated in response to mitogens.