74,921 research outputs found
Improvement of the diagnosis and management of cystic tumors of the pancreas
Pancreatic cancer is on its course on becoming the second cause of cancer related mortality. Although improvements have been made in the treatment arsenal, still only a minority of patients are able to receive treatment with curative intention. This can be attributed to the fact that most of the pancreatic cancers are diagnosed at a later stage when curative therapy is no longer possible. Thus, efforts are being made to find pancreatic cancer and its precursor lesions at an earlier stage. Intraductal papillary mucinous neoplasms (IPMN) is the most common type of cystic lesion which has the potential for malignant transformation. Hence, an accurate and early diagnosis of this entity could contribute to reverse the dismal trend of pancreatic cancer.Study I & IIAim: To identify and correlate risk factors for advanced histological findings in IPMN patients. Methods: These were retrospective studies in which patients undergoing resection for IPMN during 2008-2015 (study I) and 2004-2017 (study II) were included. Patients characteristics, radiological and histological data were prospectively collected. Results: One-hundred-fifty-two patients were included in study I and 796 patients in study II. In study I, main pancreatic duct (MPD) dilatation of 6-9.9 mm and >10 mm were associated with an increased risk of advanced IPMN histology, such as high grade dysplasia (HGD) and cancer, at odds of 2.92 (CI 1.38–6.20, p=0.005) and 2.65 (CI 1.12–6.25, p=0.02), respectively. In addition, jaundice and elevated levels of CA 19-9 were also associated with higher risk for HGD/cancer at odds of 15.36 (CI 1.94–121.22, p=0.009) and 4.15 (CI 1.90–9.05, p=0.0003), respectively. These associations remained significant at uni- and multivariable regression analysis. In study II, the results showed MPD-dilatation to be the lone significant variable associated with increased probability of HGD or IPMN-cancer at both uni- and multivariable analysis. MPD dilatation of 5-9.9 mm was associated with odds of 2.74 (CI 1.80–4.16) and 4.42 (CI 2.55–7.66) for HGD and IPMN-cancer respectively. MPD-dilatation over 10 mm was associated with greater odds of 6.57 (CI 3.94–10.98) and 15.07 (CI 8.21–27.65) for HGD and IPMN-cancer, respectively. A 5-7 mm diameter of the MPD was determined as the cut-off value to best discriminate between the lesions with low risk of malignancy to those with a high risk. Conclusions: Even a smaller dilatation of the MPD is associated with increased risk of HGD and IPMN-cancer. Dilatation of the MPD and elevated levels of CA 19-9 are important diagnostic markers of advanced histology, thereby facilitating proper selection of patients most suitable for surgery.Study III & IVAim: To define and validate the metabolic profile of patients with IPMN and serous cystic neoplasm (SCN) and to correlate the metabolite levels to histology and grade of dysplasia. Methods: Plasma and cyst fluid were prospectively collected from patients undergoing resection for IPMN and SCN. Targeted and untargeted analysis of metabolites and lipids species were performed and correlated to histology and clinical parameters. Results: From a cohort of 35 patients in study III and 57 patients in study IV several metabolites and lipids were identified in both cyst fluid and plasma. In study III, the metabolic profile showed significant alterations in the lipid pathways. An integrated metabolomic and lipidomic analysis model was able to discriminate IPMN from SCN up to 100% accuracy. The results in study IV not only validated the results from study III but also found novel metabolites able to discriminate non-cancerous lesions (low-grade IPMN and SCN) from malignant (HGD and cancer). Furthermore, specific metabolites correlated to presence of bacteria sequences in the cyst fluid. Conclusion: Analysis of the metabolic profile in cyst fluid and plasma from IPMN patients has been able to discriminate IPMN from SCN with high accuracy and also to predict the degree of dysplasia within IPMN. This method has shown potential of clinical application which in turn could improve the diagnosis of pancreatic cystic lesions.Study VAim: To investigate the rate of new recurrence and progression of known IPMNs in the remnant pancreas after pancreatic surgery and to investigate if the grade of dysplasia at first histology affects the risk of recurrence. Methods: This was a retrospective study in which patients undergoing an elective partial pancreatic resection between 2008 and 2017 were included. Patients who underwent total pancreatectomy and/or had less than 2 years of follow-up were excluded. Patient characteristics and data of radiology, histology and recurrence was collected prospectively. Clinical significant recurrence was defined as findings resulting in a change in the management of the lesion. Results: Overall 224 patients were included in the study. The overall recurrence rate was 44.6% (100/224), whereas the clinical significant recurrence rate was 30.8% (69/224). Patients older than 65 years presented 4.4 odds (CI 1.5-13.1) of recurrence and patients with “known IPMN left in remnant” had 2.6 odds (CI 1.12-5.9) of recurrence. Patients with LGD and HGD at first histology without concomitant PDAC had a clinical significant recurrence rate of 11.1% (15/135). No differences regarding risk of recurrence could be found when comparing patients with LGD to HGD (HR 1.1 [CI 0.5-2.2]). Conclusion: Patients with LGD and HGD at first histology harbor a not negligible risk of future malignant transformation and should not be overlooked. The risk is further increased if the patient is older and/or have a previously known IPMN in the remnant.The overall conclusion of the thesis is that the included studies have increased the knowledge on several aspects in the diagnosis and management of cystic tumors of the pancreas. A known radiological diagnostic marker, the dilatation of the main pancreatic duct, has been studied where the results show that even smaller dilatations over 5 mm may indicate malignancy. An upcoming field in metabolomics has been applied on pancreatic cystic neoplasms and has shown great potential as a future diagnostic method. Lastly, the post-operative management of IPMN patients has been studied where the results highlight the need for continued clinical surveillance due the risk of recurrence even after surgery.List of scientific papersI. Main pancreatic duct dilation greater than 6 mm is associated with an increased risk of high-grade dysplasia and cancer in IPMN patients. Ateeb Z*, Valente R*, Pozzi-Mucelli RM, Malgerud L, Schlieper Y, Rangelova E, Fernandez-Moro C, Löhr JM, Arnelo U, Del Chiaro M. Langenbecks Arch Surg. 2019 Feb;404(1):31-37. *Equal contribution. https://doi.org/10.1007/s00423-018-1740-8 II. Main Duct Dilatation Is the Best Predictor of High-grade Dysplasia or Invasion in Intraductal Papillary Mucinous Neoplasms of the Pancreas. Del Chiaro M*, Beckman R*, Ateeb Z, Orsini N, Rezaee N, Manos L, Valente R, Yuan C, Ding D, Margonis GA, Yin L, Cameron JL, Makary MA, Burkhart RA, Weiss MJ, He J, Arnelo U, Yu J, Wolfgang CL. Ann Surg. 2020 Dec;272(6):1118-1124. *Equal contribution. https://doi.org/10.1097/SLA.0000000000003174 III. Integrated targeted metabolomic and lipidomic analysis: A novel approach to classifying early cystic precursors to invasive pancreatic cancer. Gaiser RA*, Pessia A*, Ateeb Z*, Davanian H, Fernández Moro C, Alkharaan H, Healy K, Ghazi S, Arnelo U, Valente R, Velagapudi V, Sällberg Chen M, Del Chiaro M. Sci Rep. 2019 Jul 15;9(1):10208. *Equal contribution. https://doi.org/10.1038/s41598-019-46634-6 IV. Metabolic Characterization of Plasma and Cyst Fluid from Cystic Precursors to Pancreatic Cancer Patients Reveal Metabolic Signatures of Bacterial Infection. Morgell A*, Reisz JA*, Ateeb Z, Davanian H, Reinsbach SE, Halimi A, Gaiser R, Valente R, Arnelo U, Del Chiaro M, Chen MS, D'Alessandro A. J Proteome Res. 2021 May 7;20(5):2725-2738. *Equal contribution. https://doi.org/10.1021/acs.jproteome.1c00018 V. Recurrence and progress of IPMN in the remnant pancreas after partial resections. Ateeb Z, Franco SR, Valente R, Ghorbani P, Sparrelid E, Gilg S, Del Chiaro M, Arnelo U. [Manuscript]</p
The Benefits of Being Economics Professor A (and not Z)
Alphabetic name ordering on multi-authored academic papers, which is the convention in the economics discipline and various other disciplines, is to the advantage of people whose last name initials are placed early in the alphabet. As it turns out, Professor A, who has been a first author more often than Professor Z, will have published more articles and experienced afaster growth rate over the course of her career as a result of reputation and visibility. Moreover, authors know that name ordering matters and indeed take ordering seriously: Several characteristics of an author group composition determine the decision to deviate from the default alphabetic name order to a significant extent.performance measurement, incentives, economists, name ordering
Final word on Jersey Dutch
In this article, William Z. Shetter compares and contrasts the dialects that developed between different Dutch colonies in the New World. He explores in-depth the nuances of Jersey Dutch, and provides theories to explain how Dutch and colonial languages blended. The article is reprinted from American Speech, December 1958, Volum XXXIII, No. 4
Logarithmic variance profiles and the corresponding f-1 spectra of temperature fluctuations in turbulent Rayleigh-Bénard convection
We report experimental results for the temperature variance 2(z) and the corresponding frequency spectra P(f) in turbulent Rayleigh-Bénard convection (RBC) in a cylindrical sample of aspect ratioT= D/L = 1:00 (D = 1:12 m is the diameter and L = 1:12 m the height). The measurements were conducted in the Rayleigh-number range 1011 < Ra < 1:35 1014 and Pr ' 0:8. For Ra = 1:35x1014, 2(z) could be described well by a logarithmic dependence on the vertical position z in a range of z 1 < z < z 2 with z 1 ' 70 and z 2 = 0:1L. Here L=(2Nu) is the thickness of a thin thermal sublayer adjacent to the horizontal plate where the heat flux (denoted by the Nusselt number Nu) is carried mostly by thermal diffusion. In the log layer, we found that the temperature spectra had a significant frequency range over which P(f) f with close to 1. As Ra decreased, increased so that the log layer became thinner. At Ra = 2:05 1011, z 2 < z 1 and therefore there was no range for a log layer. Correspondingly, the temperature spectrum near the horizontal plate did not have the f1 scaling form either
Statistics of the subgrid scales after the shock-turbulence interaction
The interaction of a normal shock with isotropic turbulence (IT) represents a basic problem for studying some of the phenomena associated with high speed flows, such as hypersonic flight, supersonic combustion and Inertial Confinement Fusion (ICF). In general, in practical applications, the shock width is much smaller than the turbulence scales and the upstream turbulent Mach number is modest. In this case, recent high resolution shock-resolved Direct Numerical Simulations (DNS) (Ryu and Livescu, J. Fluid Mech., 756, R1, 2014) show that the interaction can be described by the Linear Interaction Approximation (LIA). By using LIA to alleviate the need to solve the shock, DNS post-shock data can be generated at much higher Reynolds numbers than previously possible. Here, such results with Taylor Reynolds number around are used to investigate the properties of the subgrid scales (SGS). In particular, it is shown that the shock interaction decreases the asymmetry of the SGS dissipation PDF as the shock Mach number increases, with a significant enhancement in size of the regions and magnitude of backscatter
Transition to turbulence in a qblique shock-wave/boundary-layer interaction at M=15
Direct numerical simulations are carried out for different forcing techniques to trigger transition during the interaction between an oblique shock-wave and a laminar boundary-layer at M = 1.5. Three forcing methods are used: a) forcing of oblique unstable modes, whose shape and behaviour are determined by the local linear stability theory, b) broadband free-stream acoustic disturbances, and c) a cold plasma flow control device. While the oblique-mode breakdown is dominant for low-amplitude forcing, long streaky structures drive the transition process in a high-amplitude disturbance environment. LES are also performed on the experimental setup by the Institute of Theoretical and Applied Mechanics (ITAM) from Novosibirsk State University with cold plasma actuation. As well as the disturbance type, the effect of Reynolds number and forcing amplitude will be investigated
Triangular Constellations in Flows
Particles advected on the surface of a fluid can exhibit fractal clustering. The local structure of a fractal set is described by its dimension , which is the exponent of a power-law relating the mass in a ball to its radius : . It is desirable to characterise the {\em shapes} of constellations of points sampling a fractal measure, as well as their masses. The simplest example is the distribution of shapes of triangles formed by triplets of points, which we investigate for fractals generated by chaotic dynamical systems. The most significant parameter describing the triangle shape is the ratio of its area to the radius of gyration squared. We show that the probability density of has a phase transition: is independent of and approximately uniform below a critical flow compressibility , which we estimate. For the distribution appears to be described by two power laws: when , and when
Preferential concentration of particles in compressible turbulence
The behavior of particles in compressible turbulence has been seldom investigated to date despite its importance in many natural and industrial flows. Direct numerical simulations of particle-laden compressible isotropic turbulence are performed to study the preferential concentration of particles and the underling mechanisms. It turns out that heavy particles tend to concentrate in regions of low enstrophy and high fluid density (i.e, strain regions between vortex rings), especially the particles of Kolmogorov scale, which show the largest number density. Due to the compressibility, fluid particles do not distribute uniformly as in incompressible case, but show a tendency to bunch up in high density zones. The preliminary result might give some insights into compressible turbulent transport, dispersion and mixing as well as the subgrid-scale modeling for large-eddy simulation of particle-laden compressible flows
Turbulent structures in unsteady wall-bounded flow subject to temporal acceleration
Direct numerical simulations (DNS) of a transient turbulent channel flow subject to constant temporal acceleration have been performed with a final Reynolds number of \Retau=800. The response of turbulent structures to the temporal acceleration is investigated. A significant delay in the response of turbulent flow is observed in various turbulent properties. It is found that the response of turbulent flow to temporal acceleration consists of two stages: the destruction of the initial \emph{old} turbulence, followed by the generation of \emph{new} turbulence associated with a higher number. The \emph{new} turbulence is much stronger than the \emph{old} turbulence
Incorporation of acceleration effects into the one-dimensional-turbulence model, with application to turbulent combustion and shock-turbulence interactions
One-dimensional turbulence (ODT) is a stochastic simulation in which 3D turbulence effects are captured on a notional 1D line of sight by introducing instantaneous spatial re-arrangements (maps) that represent advection by notional turbulent eddies. These eddy events incorporate the possibility of kinetic-energy changes that are equal and opposite to changes of other forms of energy such as the gravitational potential energy change due to a re-arrangement of a vertical density profile. This illustrates that motion aligned with an applied force, in this case gravitation , can be associated with energy change. Using this principle, we 1) present a model of turbulence interaction with the dilatational acceleration caused by thermal expansion in flames and show results for a turbulent counterflow flame with comparison to DNS and 2) present a model for shock-induced turbulence and show results for mixing width growth in a shock tube with comparison to experiments
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