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- Rider, Jennifer R., et al.
(author)
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iNOS expression and lethal prostate cancer in patients with localized disease
- 2017
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In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; :22S
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Journal article (peer-reviewed)abstract
- Inducible nitric oxide synthase (iNOS) has demonstrated both tumor-promoting and tumor-inhibiting effects in prostate cancer. However, the relationship between iNOS protein expression and long-term prostate cancer outcomes is unclear. We evaluated iNOS expression in tumor epithelia and stroma in 300 men with localized tumors diagnosed incidentally by transurethral resection of the prostate (TURP) in Sweden. In this extreme case-control design, cases (N=132) died of prostate cancer and controls (N=168) survived at least 8 years following diagnosis without death from prostate cancer or a competing cause. Immunohistochemistry was undertaken with a polyclonal rabbit anti-human NOS2 antibody (Abcam) and the Ventana (Roche) semi-automated staining system. Two observers individually scored the staining according to intensity and number of positive cells from 0-3. The median value across cores in each patient were then categorized as <1, >1-<2, and >2, separately for epithelial and stromal compartments. Odds ratios for lethal prostate cancer were estimated with logistic regression controlling for the matching factors (age, calendar year of diagnosis), as well as tumor stage, Gleason score, and percent tumor. iNOS was expressed by stromal-associated M1 macrophages and fibroblasts, as well as tumor cells. Gleason score was positively associated with both stromal and epithelial iNOS staining. In the stroma, there was no statistically significant association between iNOS expression and lethal prostate cancer after adjustment for clinical covariates. However, the odds of lethal prostate cancer increased with tumor expression of iNOS in the fully adjusted model. Compared to patients with the lowest category of iNOS expression, the odds ratios for lethal prostate cancer were 2.96 (95% CI: 1.26-6.96) for patients in the second category and 3.80 (95% CI: 1.45-9.97) for patients in the top category. These results suggest that iNOS may help to identify patients with aggressive prostate cancer at the time of diagnosis, or may be a therapeutic target. Given previously reported in vitro data suggesting that iNOS promotes proliferation of androgen-independent prostate tumors, future analyses will investigate association between iNOS expression and time to castration-resistant prostate cancer in this patient population.
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| 4. |
- Dán, György, et al.
(author)
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Stealth attacks and protection schemes for state estimators in power systems
- 2010
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In: 2010 1st IEEE International Conference on Smart Grid Communications, SmartGridComm 2010. - : IEEE. - 9781424465125 ; , s. 214-219
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Conference paper (peer-reviewed)abstract
- State estimators in power systems are currently used to, for example, detect faulty equipment and to route power flows. It is believed that state estimators will also play an increasingly important role in future smart power grids, as a tool to optimally and more dynamically route power flows. Therefore security of the estimator becomes an important issue. The estimators are currently located in control centers, and large numbers of measurements are sent over unencrypted communication channels to the centers. We here study stealthy false-data attacks against these estimators. We define a security measure tailored to quantify how hard attacks are to perform, and describe an efficient algorithm to compute it. Since there are so many measurement devices in these systems, it is not reasonable to assume that all devices can be made encrypted overnight in the future. Therefore we propose two algorithms to place encrypted devices in the system such as to maximize their utility in terms of increased system security. We illustrate the effectiveness of our algorithms on two IEEE benchmark power networks under two attack and protection cost models.
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| 6. |
- McLachlan, Robert, et al.
(author)
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Collective symplectic integrators
- 2014
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In: Nonlinearity. - : Institute of Physics Publishing (IOPP). - 0951-7715 .- 1361-6544. ; 27:6, s. 1525-1542
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Journal article (peer-reviewed)abstract
- We construct symplectic integrators for Lie-Poisson systems. The integrators are standard symplectic (partitioned) Runge-Kutta methods. Their phase space is a symplectic vector space equipped with a Hamiltonian action with momentum map J whose range is the target Lie-Poisson manifold, and their Hamiltonian is collective, that is, it is the target Hamiltonian pulled back by J. The method yields, for example, a symplectic midpoint rule expressed in 4 variables for arbitrary Hamiltonians on so(3)*. The method specializes in the case that a sufficiently large symmetry group acts on the fibres of J, and generalizes to the case that the vector space carries a bifoliation. Examples involving many classical groups are presented.
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| 7. |
- Ahmad, Yousif, et al.
(author)
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Coronary Hemodynamics in Patients With Severe Aortic Stenosis and Coronary Artery Disease Undergoing Transcatheter Aortic Valve Replacement : Implications for Clinical Indices of Coronary Stenosis Severity
- 2018
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In: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1876-7605 .- 1936-8798. ; 11:20, s. 2019-2031
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Journal article (peer-reviewed)abstract
- OBJECTIVES: In this study, a systematic analysis was conducted of phasic intracoronary pressure and flow velocity in patients with severe aortic stenosis (AS) and coronary artery disease, undergoing transcatheter aortic valve replacement (TAVR), to determine how AS affects: 1) phasic coronary flow; 2) hyperemic coronary flow; and 3) the most common clinically used indices of coronary stenosis severity, instantaneous wave-free ratio and fractional flow reserve.BACKGROUND: A significant proportion of patients with severe aortic stenosis (AS) have concomitant coronary artery disease. The effect of the valve on coronary pressure, flow, and the established invasive clinical indices of stenosis severity have not been studied.METHODS: Twenty-eight patients (30 lesions, 50.0% men, mean age 82.1 ± 6.5 years) with severe AS and coronary artery disease were included. Intracoronary pressure and flow assessments were performed at rest and during hyperemia immediately before and after TAVR.RESULTS: Flow during the wave-free period of diastole did not change post-TAVR (29.78 ± 14.9 cm/s vs. 30.81 ± 19.6 cm/s; p = 0.64). Whole-cycle hyperemic flow increased significantly post-TAVR (33.44 ± 13.4 cm/s pre-TAVR vs. 40.33 ± 17.4 cm/s post-TAVR; p = 0.006); this was secondary to significant increases in systolic hyperemic flow post-TAVR (27.67 ± 12.1 cm/s pre-TAVR vs. 34.15 ± 17.5 cm/s post-TAVR; p = 0.02). Instantaneous wave-free ratio values did not change post-TAVR (0.88 ± 0.09 pre-TAVR vs. 0.88 ± 0.09 post-TAVR; p = 0.73), whereas fractional flow reserve decreased significantly post-TAVR (0.87 ± 0.08 pre-TAVR vs. 0.85 ± 0.09 post-TAVR; p = 0.001).CONCLUSIONS: Systolic and hyperemic coronary flow increased significantly post-TAVR; consequently, hyperemic indices that include systole underestimated coronary stenosis severity in patients with severe AS. Flow during the wave-free period of diastole did not change post-TAVR, suggesting that indices calculated during this period are not vulnerable to the confounding effect of the stenotic aortic valve.
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- Escala-Garcia, M, et al.
(author)
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Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19787-
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Journal article (peer-reviewed)abstract
- Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
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