Surveillance for pancreatic cancer in high-risk individuals

Background Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC

Urban Air Mobility Airspace Integration Concepts and Considerations

Urban Air Mobility (UAM) - defined as safe and efficient air traffic operations in a metropolitan area for manned aircraft and unmanned aircraft systems - is being researched and developed by industry, academia, and government. Significant resources have been invested toward cultivating an ecosystem for Urban Air Mobility that includes manufacturers of electric vertical takeoff and landing aircraft, builders of takeoff and landing areas, and researchers of the airspace integration concepts, technologies, and procedures needed to conduct Urban Air Mobility operations safely and efficiently alongside other airspace users. This paper provides high-level descriptions of both emergent and early expanded operational concepts for Urban Air Mobility that NASA is developing. The scope of this work is defined in terms of missions, aircraft, airspace, and hazards. Past and current Urban Air Mobility operations are also reviewed, and the considerations for the data exchange architecture and communication, navigation, and surveillance requirements are also discussed. This paper will serve as a starting point to develop a framework for NASA's Urban Air Mobility airspace integration research and development efforts with partners and stakeholders that could include fast-time simulations, human-in-the-loop (HITL) simulations, and flight demonstrations

Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect - a histopathological and immunohistochemical study

BACKGROUND: Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host reponse. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response. PATIENTS AND METHODS: The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing. RESULTS: Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001). CONCLUSIONS: We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer

On Predicting Mössbauer Parameters of Iron-Containing Molecules with Density-Functional Theory

The performance of six frequently used density functional theory (DFT) methods (RPBE, OLYP, TPSS, B3LYP, B3LYP*, and TPSSh) in the prediction of Mössbauer isomer shifts(δ) and quadrupole splittings (ΔEQ) is studied for an extended and diverse set of Fe complexes. In addition to the influence of the applied density functional and the type of the basis set, the effect of the environment of the molecule, approximated with the conducting-like screening solvation model (COSMO) on the computed Mössbauer parameters, is also investigated. For the isomer shifts the COSMO-B3LYP method is found to provide accurate δ values for all 66 investigated complexes, with a mean absolute error (MAE) of 0.05 mm s–1 and a maximum deviation of 0.12 mm s–1. Obtaining accurate ΔEQ values presents a bigger challenge; however, with the selection of an appropriate DFT method, a reasonable agreement can be achieved between experiment and theory. Identifying the various chemical classes of compounds that need different treatment allowed us to construct a recipe for ΔEQ calculations; the application of this approach yields a MAE of 0.12 mm s–1 (7% error) and a maximum deviation of 0.55 mm s–1 (17% error). This accuracy should be sufficient for most chemical problems that concern Fe complexes. Furthermore, the reliability of the DFT approach is verified by extending the investigation to chemically relevant case studies which include geometric isomerism, phase transitions induced by variations of the electronic structure (e.g., spin crossover and inversion of the orbital ground state), and the description of electronically degenerate triplet and quintet states. Finally, the immense and often unexploited potential of utilizing the sign of the ΔEQ in characterizing distortions or in identifying the appropriate electronic state at the assignment of the spectral lines is also shown

Active symbols and internal models: Towards a cognitive connectionism

In the first section of the article, we examine some recent criticisms of the connectionist enterprise: first, that connectionist models are fundamentally behaviorist in nature (and, therefore, non-cognitive), and second that connectionist models are fundamentally associationist in nature (and, therefore, cognitively weak). We argue that, for a limited class of connectionist models (feed-forward, pattern-associator models), the first criticism is unavoidable. With respect to the second criticism, we propose that connectionist models are fundamentally associationist but that this is appropriate for building models of human cognition. However, we do accept the point that there are cognitive capacities for which any purely associative model cannot provide a satisfactory account. The implication that we draw from is this is not that associationist models and mechanisms should be scrapped, but rather that they should be enhanced.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45877/1/146_2005_Article_BF01889764.pd

Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium

Surgical oncolog