Finite Element Flow Simulations of the EUROLIFT DLR-F11 High Lift Configuration

This paper presents flow simulation results of the EUROLIFT DLR-F11 multi-element wing configuration, obtained with a highly scalable finite element solver, PHASTA. This work was accomplished as a part of the 2nd high lift prediction workshop. In-house meshes were constructed with increasing mesh density for analysis. A solution adaptive approach was used as an alternative and its effectiveness was studied by comparing its results with the ones obtained with other meshes. Comparisons between the numerical solution obtained with unsteady RANS turbulence model and available experimental results are provided for verification and discussion. Based on the observations, future direction for adaptive research and simulations with higher fidelity turbulence models is outlined.Comment: 52nd Aerospace Sciences Meetin

An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors.

To address the biological heterogeneity of lung cancer, we studied 199 lung adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for major known somatic mutations in this cancer. This showed non-random patterns of copy number alterations significantly linked to EGFR and KRAS mutation status and to distinct clinical outcomes, and led to the discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p. DUSP4 is involved in negative feedback control of EGFR signaling, and we provide functional validation for its role as a growth suppressor in EGFR-mutant lung adenocarcinoma. DUSP4 loss also associates with p16/CDKN2A deletion and defines a distinct clinical subset of lung cancer patients. Another novel observation is that of a reciprocal relationship between EGFR and LKB1 mutations. These results highlight the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers

Bioenergetic Adaptations in Chemoresistant Ovarian Cancer Cells.

Earlier investigations have revealed that tumor cells undergo metabolic reprogramming and mainly derive their cellular energy from aerobic glycolysis rather than oxidative phosphorylation even in the presence of oxygen. However, recent studies have shown that certain cancer cells display increased oxidative phosphorylation or high metabolically active phenotype. Cellular bioenergetic profiling of 13 established and 12 patient derived ovarian cancer cell lines revealed significant bioenergetics diversity. The bioenergetics phenotype of ovarian cancer cell lines correlated with functional phenotypes of doubling time and oxidative stress. Interestingly, chemosensitive cancer cell lines (A2780 and PEO1) displayed a glycolytic phenotype while their chemoresistant counterparts (C200 and PEO4) exhibited a high metabolically active phenotype with the ability to switch between oxidative phosphorylation or glycolysis. The chemosensitive cancer cells could not survive glucose deprivation, while the chemoresistant cells displayed adaptability. In the patient derived ovarian cancer cells, a similar correlation was observed between a high metabolically active phenotype and chemoresistance. Thus, ovarian cancer cells seem to display heterogeneity in using glycolysis or oxidative phosphorylation as an energy source. The flexibility in using different energy pathways may indicate a survival adaptation to achieve a higher \u27cellular fitness\u27 that may be also associated with chemoresistance

The interplay of growth differentiation factor 15 (GDF15) expression and M2 macrophages during prostate carcinogenesis

M2 (tumor-supportive) macrophages may upregulate growth differentiation factor 15 (GDF15), which is highly expressed in prostate tumors, but the combined utility of these markers as prognostic biomarkers are unclear. We retrospectively studied 90 prostate cancer cases that underwent radical prostatectomy as their primary treatment and were followed for biochemical recurrence (BCR). These cases also had a benign prostate biopsy at least 1 year or more before their prostate cancer surgery. Using computer algorithms to analyze digitalized immunohistochemically stained slides, GDF15 expression and the presence of M2 macrophages based on the relative density of CD204- and CD68-positive macrophages were measured in prostate: (i) benign biopsy, (ii) cancer and (iii) tumor-adjacent benign (TAB) tissue. Both M2 macrophages (P = 0.0004) and GDF15 (P \u3c 0.0001) showed significant inter-region expression differences. Based on a Cox proportional hazards model, GDF15 expression was not associated with BCR but, in men where GDF15 expression differences between cancer and TAB were highest, the risk of BCR was significantly reduced (hazard ratio = 0.26; 95% confidence interval = 0.09-0.94). In addition, cases with high levels of M2 macrophages in prostate cancer had almost a 5-fold increased risk of BCR (P = 0.01). Expression of GDF15 in prostate TAB was associated with M2 macrophage levels in both prostate cancer and TAB and appeared to moderate M2-macrophage-associated BCR risk. In summary, the relationship of GDF15 expression and CD204-positive M2 macrophage levels is different in a prostate tumor environment compared with an earlier benign biopsy and, collectively, these markers may predict aggressive disease

Racial differences in the systemic inflammatory response to prostate cancer

Systemic inflammation may increase risk for prostate cancer progression, but the role it plays in prostate cancer susceptibility is unknown. From a cohort of over 10,000 men who had either a prostate biopsy or transurethral resection that yielded a benign finding, we analyzed 517 incident prostate cancer cases identified during follow-up and 373 controls with one or more white blood cell tests during a follow-up period between one and 18 years. Multilevel, multivariable longitudinal models were fit to two measures of systemic inflammation, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR), to determine NLR and MLR trajectories associated with increased risk for prostate cancer. For both measures, we found no significant differences in the trajectories by case/control status, however in modeling NLR trajectories there was a significant interaction between race (white or Black and case-control status. In race specific models, NLR and MLR values were consistently higher over time among white controls than white cases while case-control differences in NLR and MLR trajectories were not apparent among Black men. When cases were classified as aggressive as compared to non-aggressive, the case-control differences in NLR and MLR values over time among white men were most apparent for non-aggressive cases. For NLR among white men, significant case-control differences were observed for the entire duration of observation for men who had inflammation in their initial prostate specimen. It is possible that, among white men, monitoring of NLR and MLR trajectories after an initial negative biopsy may be useful in monitoring prostate cancer risk

Evaluating initial spine trauma response: injury time to trauma center in PA, USA.

Historical perceptions regarding the severity of traumatic spinal cord injury has led to considerable disparity in triage to tertiary care centers. This article retrospectively reviews a large regional trauma database to analyze whether the diagnosis of spinal trauma affected patient transfer timing and patterns. The Pennsylvania Trauma database was retrospectively reviewed. All acute trauma patient entries for level I and II centers were categorized for diagnosis, mechanism, and location of injury, analyzing transportation modality and its influence on time of arrival. A total of 1162 trauma patients were identified (1014 blunt injuries, 135 penetrating injuries and 12 other) with a mean transport time of 3.9 hours and a majority of patients arriving within 7 hours (\u3e75%). Spine trauma patients had the longest mean arrival time (5.2 hours) compared to blunt trauma (4.2 hours), cranial neurologic injuries (4.35 hours), and penetrating injuries (2.13 hours,

Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145266/1/his13526_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145266/2/his13526.pd

Growth and differentiation factor 15 and NF-κB expression in benign prostatic biopsies and risk of subsequent prostate cancer detection

Growth and differentiation factor 15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1), may act as both a tumor suppressor and promotor and, by regulating NF-κB and macrophage signaling, promote early prostate carcinogenesis. To determine whether expression of these two inflammation-related proteins affect prostate cancer susceptibility, dual immunostaining of benign prostate biopsies for GDF-15 and NF-κB was done in a study of 503 case-control pairs matched on date, age, and race, nested within a historical cohort of 10,478 men. GDF-15 and NF-κB expression levels were positively correlated (r = 0.39; p \u3c 0.0001), and both were significantly lower in African American (AA) compared with White men. In adjusted models that included both markers, the odds ratio (OR) for NF-κB expression was statistically significant, OR =0.87; p = 0.03; 95% confidence interval (CI) =0.77-0.99, while GDF-15 expression was associated with a nominally increased risk, OR =1.06; p = 0.27; 95% CI =0.96-1.17. When modeling expression levels by quartiles, the highest quartile of NF-κB expression was associated with almost a fifty percent reduction in prostate cancer risk (OR =0.51; p = 0.03; 95% CI =0.29-0.92). In stratified models, NF-κB had the strongest negative association with prostate cancer in non-aggressive cases (p = 0.03), older men (p = 0.03), and in case-control pairs with longer follow-up (p = 0.02). Risk associated with GDF-15 expression was best fit using nonlinear regression modeling where both first (p = 0.02) and second (p = 0.03) order GDF-15 risk terms were associated with significantly increased risk. This modeling approach also revealed significantly increased risk associated with GDF-15 expression for subsamples defined by AA race, aggressive disease, younger age, and in case-control pairs with longer follow-up. Therefore, although positively correlated in benign prostatic biopsies, NF-κB and GDF-15 expression appear to exert opposite effects on risk of prostate tumor development

A systematic review of participatory scenario planning to envision mountain social-ecological systems futures

Mountain social-ecological systems (MtSES) provide crucial ecosystem services to over half of humanity. However, populations living in these highly varied regions are now confronted by global change. It is critical that they are able to anticipate change to strategically manage resources and avoid potential conflict. Yet, planning for sustainable, equitable transitions for the future is a daunting task, considering the range of uncertainties and the unique character of MtSES. Participatory scenario planning (PSP) can help MtSES communities by critically reflecting on a wider array of innovative pathways for adaptive transformation. Although the design of effective approaches has been widely discussed, how PSP has been employed in MtSES has yet to be examined. Here, we present the first systematic global review of single- and multiscalar, multisectoral PSP undertaken in MtSES, in which we characterize the process, identify strengths and gaps, and suggest effective ways to apply PSP in MtSES. We used a nine-step process to help guide the analysis of 42 studies from 1989 screened articles. Our results indicate a steady increase in relevant studies since 2006, with 43% published between 2015 and 2017. These studies encompass 39 countries, with over 50% in Europe. PSP in MtSES is used predominantly to build cooperation, social learning, collaboration, and decision support, yet meeting these objectives is hindered by insufficient engagement with intended end users. MtSES PSP has focused largely on envisioning themes of governance, economy, land use change, and biodiversity, but has overlooked themes such as gender equality, public health, and sanitation. There are many avenues to expand and improve PSP in MtSES: to other regions, sectors, across a greater diversity of stakeholders, and with a specific focus on MtSES paradoxes. Communicating uncertainty, monitoring and evaluating impacts, and engendering more comparative approaches can further increase the utility of PSP for addressing MtSES challenges, with lessons for other complex social-ecological systems. © 2020 by the author(s)

Low Levels of Low-Density Lipoprotein Cholesterol Increase the Risk of Post-Thrombectomy Delayed Parenchymal Hematoma

Purpose Low levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to increase the risk of hemorrhagic transformation (HT) following acute ischemic stroke. However, the literature on the relationship between LDL-C levels and post-thrombectomy HT is sparse. The aim of our study is to investigate the association between LDL-C and delayed parenchymal hematoma (PH) that was not seen on immediate post-thrombectomy dual-energy computed tomography (DECT). Materials and Methods A retrospective analysis was conducted on all patients with anterior circulation large vessel occlusion who underwent thrombectomy at a comprehensive stroke center from 2018–2021. Per institutional protocol, all patients received DECT immediately post-thrombectomy and magnetic resonance imaging or CT at 24 hours. The presence of immediate hemorrhage was assessed by DECT, while delayed PH was assessed by 24-hour imaging. Multivariable analysis was performed to identify predictors of delayed PH. Patients with hemorrhage on immediate post-thrombectomy DECT were excluded to select only those with delayed PH. Results Of 159 patients without hemorrhage on immediate post-thrombectomy DECT, 18 (11%) developed delayed PH on 24-hour imaging. In multivariable analysis, LDL-C (odds ratio [OR], 0.76; P=0.038; 95% confidence interval [CI], 0.59–0.99; per 10 mg/dL increase) independently predicted delayed PH. High-density lipoprotein cholesterol, triglyceride, and statin use were not associated. After adjusting for potential confounders, LDL-C ≤50 mg/dL was associated with an increased risk of delayed PH (OR, 5.38; P=0.004; 95% CI, 1.70–17.04), while LDL-C >100 mg/dL was protective (OR, 0.26; P=0.041; 95% CI, 0.07–0.96). Conclusion LDL-C ≤50 mg/dL independently predicted delayed PH following thrombectomy and LDL-C >100 mg/dL was protective, irrespective of statin. Thus, patients with low LDL-C levels may warrant vigilant monitoring and necessary interventions, such as blood pressure control or anticoagulation management, following thrombectomy even in the absence of hemorrhage on immediate post-thrombectomy DECT