Contribution of routine brain MRI to the differential diagnosis of parkinsonism: a 3-year prospective follow-up study

Various signs on routine brain MRI can help differentiate between Parkinson’s disease (PD) and the various forms of atypical parkinsonism (AP). Here, we evaluate what routine brain MRI contributes to the clinical diagnosis, in both early and advanced disease stages. We performed a prospective observational study in 113 patients with parkinsonism, but without definite diagnosis upon inclusion. At baseline, patients received a structured interview, comprehensive and standardized neurological assessment, and brain MRI. The silver standard diagnosis was made after 3 years of follow-up (PD n = 43, AP n = 57), which was based on disease progression, repeat standardized neurological examination and response to treatment. The clinical diagnosis was classified as having either ‘low certainty’ (lower than 80%) or ‘high certainty’ (80% or higher). The added diagnostic yield of baseline MRI results were then studied relative to clinical neurological evaluation at presentation, and at follow-up. Sensitivity and specificity for separating AP from PD were calculated for all potentially distinguishing MRI abnormalities described previously in the literature. MRI abnormalities showed moderate to high specificity but limited sensitivity for the diagnosis of AP. These MRI abnormalities contributed little over and above the clinically based diagnosis, except when the clinical diagnosis was uncertain. For these patients, presence of putaminal or cerebellar atrophy was particularly indicative of AP. Routine brain MRI has limited added value for differentiating between PD and AP when clinical certainty is already high, but has some diagnostic value when the clinical diagnosis is still uncertain

Proof of concept study for fuselage boundary layer ingesting propulsion

Key results from the EU H2020 project CENTRELINE are presented. The research activities undertaken to demonstrate the proof of concept (technology readiness level—TRL 3) for the so-called propulsive fuselage concept (PFC) for fuselage wake-filling propulsion integration are discussed. The technology application case in the wide-body market segment is motivated. The developed performance bookkeeping scheme for fuselage boundary layer ingestion (BLI) propulsion integration is reviewed. The results of the 2D aerodynamic shape optimization for the bare PFC configuration are presented. Key findings from the high-fidelity aero-numerical simulation and aerodynamic validation testing, i.e., the overall aircraft wind tunnel and the BLI fan rig test campaigns, are discussed. The design results for the architectural concept, systems integration and electric machinery pre-design for the fuselage fan turbo-electric power train are summarized. The design and performance implications on the main power plants are analyzed. Conceptual design solutions for the mechanical and aero-structural integration of the BLI propulsive device are introduced. Key heuristics deduced for PFC conceptual aircraft design are presented. Assessments of fuel burn, NOx emissions, and noise are presented for the PFC aircraft and benchmarked against advanced conventional technology for an entry-into-service in 2035. The PFC design mission fuel benefit based on 2D optimized PFC aero-shaping is 4.7%.European Union’s Horizon 2020 research and innovation programme. Grant agreement no. 72324

Contribution of routine brain MRI to the differential diagnosis of parkinsonism: a 3-year prospective follow-up study

Abstract Various signs on routine brain MRI can help differentiate between Parkinson's disease (PD) and the various forms of atypical parkinsonism (AP). Here, we evaluate what routine brain MRI contributes to the clinical diagnosis, in both early and advanced disease stages. We performed a prospective observational study in 113 patients with parkinsonism, but without definite diagnosis upon inclusion. At baseline, patients received a structured interview, comprehensive and standardized neurological assessment, and brain MRI. The silver standard diagnosis was made after 3 years of follow-up (PD n = 43, AP n = 57), which was based on disease progression, repeat standardized neurological examination and response to treatment. The clinical diagnosis was classified as having either 'low certainty' (lower than 80%) or 'high certainty' (80% or higher). The added diagnostic yield of baseline MRI results were then studied relative to clinical neurological evaluation at presentation, and at follow-up. Sensitivity and specificity for separating AP from PD were calculated for all potentially distinguishing MRI abnormalities described previously in the literature. MRI abnormalities showed moderate to high specificity but limited sensitivity for the diagnosis of AP. These MRI abnormalities contributed little over and above the clinically based diagnosis, except when the clinical diagnosis was uncertain. For these patients, presence of putaminal or cerebellar atrophy was particularly indicative of AP. Routine brain MRI has limited added value for differentiating between PD and AP when clinical certainty is already high, but has some diagnostic value when the clinical diagnosis is still uncertain

<i>De novo</i> design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy

Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of 4-fold symmetrical (β/α)(8)-barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of sidechain-backbone hydrogen bonding for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical with the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has only sampled a subset of the sequence space available to the TIM-barrel fold. The ability to de novo design TIM-barrels opens new possibilities for custom-made enzymes

Discrimination between Metastases and Glioblastomas multiforme based on morphometrical analysis of MR images

Contains fulltext : 84443.pdf (publisher's version ) (Open Access)7 p

Niektóre przyczyny wzrostu szybkości katalitycznego uwodornienia tłuszczów wskutek oddziaływania aktywnej ziemi bielącej w układzie reakcyjnym

The increase of hydrogenation rate of oils after the addition of bleaching earth to the reaction system is due to the adsorption of poisons present in oils, and may be also due to the adsorption of these inhibitors, which are formed or undergo the transformation during the progress of the hydrogenation in the presence of catalyst. The direct interaction of bleaching earth with the catalyst is also possible.Badano wpływ ziemi bielącej użytej w procesie odbarwiania i „traktowania" oleju rzepakowego na kinetykę uwodornienia otrzymanych olejów w obecności katalizatora beznośnikowego oraz na nośniku. Wyniki porównano z szybkością uwodornienia w obecności ziemi bielącej wprowadzonej do reaktora. Analogiczne badania wykonano w układzie modelowym, zawierającym wprowadzone mydła sodowe, fosfolipidy oraz ITC-allilu. W tym układzie oceniono również kinetykę uwodornienia w obecności ziemi bielącej o podwyższonej kwasowości. Procesy prowadzono w reaktorze typu "dead end" z automatyczną rejestracją ilości pochłoniętego wodoru. Stwierdzono największą szybkość uwodornienia, kiedy ziemia bieląca była składnikiem zarówno układu reakcyjnego zawierającego olej rzepakowy, jak też układu modelowego. Wzrost szybkości reakcji wywołany był więc nie tylko adsorpcją trucizn z oleju, ale prawdopodobnie również sorpcją tych substancji toksycznych, które powstają lub ulegają transformacji w warunkach prowadzenia reakcji uwodornienia (w obecności katalizatora). Możliwe było również oddziaływanie ziemi bielącej jako promotora na katalizator. Wzrost kwasowości adsorbenta znacznie zwiększa szybkość uwodornienia oleju zawierającego mydła sodowe na skutek rozkładu ich do mniej toksycznych kwasów tłuszczowych. W obecności pozostałych trucizn szybkość procesu wzrastała, kiedy prowadzono go z udziałem katalizatora beznośnikowego lub malała dla katalizatora na nośniku