Tudásmenedzsment és a felsőoktatási intézmény, mint vállalat = Knowledge Management and the University as a Company

Purpose: ALK rearrangement detection using FISH is the standard test to identify patients with non–small cell lung carcinoma (NSCLC) eligible for treatment with ALK inhibitors. Recently, ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH. Experimental Design: Patients with stage IV NSCLC treated with crizotinib were selected. Tumor response was assessed. ALK rearrangements were detected by FISH (Vysis ALK-break-apart FISH-Probe KIT) and IHC [Ventana ALK (D5F3) CDx assay]. Cohorts of patients with ALK-FISH–positive advanced NSCLC from four other hospitals were used for validation. Results: Twenty-nine consecutive patients with ALK-positive advanced NSCLC diagnosed by FISH and/or IHC on small biopsies or fine-needle aspirations (FNA) were treated with ALK inhibitors. All ALK-IHC–positive patients responded to crizotinib except three with primary resistance. No tumor response was observed in 13 ALK-FISH–positive but ALK-IHC–negative patients. This was confirmed in an external cohort of 16 patients. Receiver operator characteristic (ROC) curves for ALK-IHC and ALK-FISH compared with treatment outcome showed that dichotomous ALK-IHC outperforms ALK-FISH [tumor response area under the curve: (AUC), 0.86 vs. 0.64, P ¼ 0.03; progression-free survival (PFS): AUC 0.86 vs. 0.36, P ¼ 0.005; overall survival (OS): AUC, 0.78 vs. 0.41, P ¼ 0.01, respectively]. Conclusions: Dichotomous ALK-IHC is superior to ALK-FISH on small biopsies and FNA to predict tumor response and survival to crizotinib for patients with advanced NSCLC. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select patients with NSCLC who benefit from ALK-targeting therapy

Systematic investigation of the elastic proton-deuteron differential cross section at intermediate energies

To investigate the importance of three-nucleon forces (3NF) systematically over a broad range of intermediate energies, the differential cross sections of elastic proton-deuteron scattering have been measured at proton bombarding energies of 108, 120, 135, 150, 170 and 190 MeV at center-of-mass angles between $30^\circ$ and $170^\circ$. Comparisons with Faddeev calculations show unambiguously the shortcomings of calculations employing only two-body forces and the necessity of including 3NF. They also show the limitations of the latest few-nucleon calculations at backward angles, especially at higher beam energies. Some of these discrepancies could be partially due to relativistic effects. Data at lowest energy are also compared with a recent calculation based on \chipt

The modelled surface mass balance of the Antarctic Peninsula at 5.5 km horizontal resolution

This study presents a high-resolution (~ 5.5 km) estimate of Surface Mass Balance (SMB) over the period 1979–2014 for the Antarctic Peninsula (AP), generated by the regional atmospheric climate model RACMO2.3 and a Firn Densification Model (FDM). RACMO2.3 is used to force the FDM, which calculates processes in the snowpack, such as meltwater percolation, refreezing and runoff. We evaluate model output with 132 in-situ SMB observations and discharge rates from 6 glacier drainage basins, and find that the model realistically simulates the strong spatial variability in precipitation, but that significant biases remain as a result of the highly complex topography of the AP. It is also clear that the observations significantly underrepresent the high-accumulation regimes. The SMB map reveals large accumulation gradients, with precipitation values above 3000 mm we yr−1 over the western AP (WAP) and below 500 mm we yr−1 on the eastern AP (EAP), not resolved by coarser data-sets such as ERA-Interim. The other SMB components are one order of magnitude smaller, with drifting snow sublimation the largest ablation term removing up to 100 mm we yr−1 of mass. Snowmelt is widespread over the AP, reaching 500 mm we yr−1 towards the northern ice shelves, but the meltwater mostly refreezes. As a result runoff fluxes are low, but still considerable (200 mm we yr−1) over the Larsen (B/C), Wilkins and George VI ice shelves. The average AP ice sheet integrated SMB, including ice shelves (an area of 4.1 × 105 km2), is estimated at 351 Gt yr−1 with an interannual variability of 58 Gt yr−1, which is dominated by precipitation (PR) (365 ± 57 Gt yr−1). The WAP (2.4 × 105 km2) SMB (276 ± 47 Gt yr−1), where PR is large (276 ± 47 Gt yr−1), dominates over the EAP (1.7 × 105 km2) SMB (75 ± 11 Gt yr−1) and PR (84 ± 11 Gt yr−1). Total sublimation is 11 ± 2 Gt yr−1 and meltwater runoff into the ocean is 4 ± 4 Gt yr−1. There are no significant trends in any of the AP SMB components, except for snowmelt that shows a significant decrease over the last 36 years (−0.36 Gt yr−2)

International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

The anisotropic hyperelastic biomechanical response of the vocal ligament and implications for frequency regulation: A case study

One of the primary mechanisms to vary one's vocal frequency is through vocal fold length changes. As stress and deformation are linked to each other, it is hypothesized that the anisotropy in the biomechanical properties of the vocal fold tissue would affect the phonation characteristics. A biomechanical model of vibrational frequency rise during vocal fold elongation is developed which combines an advanced biomechanical characterization protocol of the vocal fold tissue with continuum beam models. Biomechanical response of the tissue is related to a microstructurally informed, anisotropic, nonlinear hyperelastic constitutive model. A microstructural characteristic (the dispersion of collagen) was represented through a statistical orientation function acquired from a second harmonic generation image of the vocal ligament. Continuum models of vibration were constructed based upon Euler–Bernoulli and Timoshenko beam theories, and applied to the study of the vibration of a vocal ligament specimen. From the natural frequency predictions in dependence of elongation, two competing processes in frequency control emerged, i.e., the applied tension raises the frequency while simultaneously shear deformation lowers the frequency. Shear becomes much more substantial at higher modes of vibration and for highly anisotropic tissues. The analysis was developed as a case study based on a human vocal ligament specimen

Quality of spirometry and related diagnosis in primary care with a focus on clinical use

Contains fulltext : 220998.pdf (publisher's version ) (Open Access

Low-lying GT(+) strength in Co-64 studied via the Ni-64(d,He-2)Co-64 reaction

The Ni-64(d,He-2)Co-64 reaction was studied at the AGOR cyclotron of KVI, Groningen, with the Big-Bite Spectrometer and the EuroSuperNova detector using a 171-MeV deuteron beam. An energy resolution of about 110 keV was achieved. In addition to the J(pi) = 1(+) ground state, several other 1(+) states could be identified in Co-64 and the strengths of the corresponding Gamow-Teller transitions were determined. The obtained strength distribution was compared with theoretical predictions and former (n,p) experimental results and displayed a good agreement. Due to the good energy resolution, detailed spectroscopic information was obtained, which supplements the data base needed for network calculations for supernova scenarios

Comparison of haemodynamic- and electroencephalographic-monitored effects evoked by four combinations of effect-site concentrations of propofol and remifentanil, yielding a predicted tolerance to laryngoscopy of 90%

This prospective study evaluates haemodynamic and electroencephalographic effects observed when administering four combinations of effect-site concentrations of propofol (Ce-PROP) and remifentanil (Ce-REMI), all yielding a single predicted probability of tolerance of laryngoscopy of 90% (P-TOL = 90%) according to the Bouillon interaction model. We aimed to identify combinations of Ce-PROP and Ce-REMI along a single isobole of P-TOL that result in favourable hypnotic and haemodynamic conditions. This knowledge could be of advantage in the development of drug advisory monitoring technology. 80 patients (18-90 years of age, ASA I-III) were randomized into four groups and titrated towards Ce-PROP (Schnider model, ug.ml(-1)) and Ce-REMI (Minto model, ng.ml(-1)) of respectively 8.6 and 1, 5.9 and 2, 3.6 and 4 and 2.0 and 8. After eleven minutes of equilibration, baseline measurements of haemodynamic endpoints and bispectral index were compared with three minutes of responsiveness measurements after laryngoscopy. Before laryngoscopy, bispectral index differed significantly (p < 0.0001) between groups in concordance with Ce-PROP. Heart rate decreased with increasing Ce-REMI (p = 0.001). The haemodynamic and arousal responses evoked by laryngoscopy were not significantly different between groups, but Ce-PROP = 3.6 mu g.ml(-1) and Ce-REMI = 4 ng.ml(-1) evoked the lowest median value for increment HR and increment SAP after laryngoscopy. This study provides clinical insight on the haemodynamic and hypnotic consequences, when a model based predicted P-TOL is used as a target for combined effect-site controlled target- controlled infusion of propofol and remifentanil. Heart rate and bispectral index were significantly different between groups despite a theoretical equipotency for P-TOL, suggesting that each component of the anaesthetic state (immobility, analgesia, and hypnotic drug effect) should be considered as independent neurophysiological and pharmacological phenomena. However, claims of (in)accuracy of the predicted P-TOL must be considered preliminary because larger numbers of observations are required for that goal

Diffusive and ballistic current spin-polarization in magnetron-sputtered L1o-ordered epitaxial FePt

We report on the structural, magnetic, and electron transport properties of a L1o-ordered epitaxial iron-platinum alloy layer fabricated by magnetron-sputtering on a MgO(001) substrate. The film studied displayed a long range chemical order parameter of S~0.90, and hence has a very strong perpendicular magnetic anisotropy. In the diffusive electron transport regime, for temperatures ranging from 2 K to 258 K, we found hysteresis in the magnetoresistance mainly due to electron scattering from magnetic domain walls. At 2 K, we observed an overall domain wall magnetoresistance of about 0.5 %. By evaluating the spin current asymmetry alpha = sigma_up / sigma_down, we were able to estimate the diffusive spin current polarization. At all temperatures ranging from 2 K to 258 K, we found a diffusive spin current polarization of > 80%. To study the ballistic transport regime, we have performed point-contact Andreev-reflection measurements at 4.2 K. We obtained a value for the ballistic current spin polarization of ~42% (which compares very well with that of a polycrystalline thin film of elemental Fe). We attribute the discrepancy to a difference in the characteristic scattering times for oppositely spin-polarized electrons, such scattering times influencing the diffusive but not the ballistic current spin polarization.Comment: 22 pages, 13 figure