Naar een geïntegreerde interventie in de organisatie van de informatievoorziening

Binnen het managementdomein van informatievoorziening is een aantal disciplines ontstaan, allen gericht op een optimale inzet van ICT in organisaties. Zo tref je ook binnen het Ngi de afdelingen Informatiemanagement, Architectuur en Governance aan, die elkaar inhoudelijk lijken te overlappen. Deze disciplines kunnen elkaar echter ook versterken als ze tot een geïntegreerde interventie leiden in de werkpraktijk van organisatie en informatie. In onderstaande, overigens fictieve casus laten de auteurs zien dat de disciplines weliswaar een specifiek perspectief hanteren, maar ook complementair zijn en daarmee een sterk interventiemiddel vormen bij ICT-problemen in organisaties

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Motor function impairment is an early sign of CLN3 disease

Objective To delineate timing of motor decline in CLN3 disease. Methods Motor function, assessed by the 6-Minute Walk Test (6MWT), was evaluated repeatedly in 15 patients with CLN3 disease, resulting in 65 test results and during one occasion in 2 control cohorts. One control cohort (n = 14) had isolated visual impairment; a second cohort (n = 12) exhibited visual impairment in combination with neurologic impairments. Based on 6MWT reference values in healthy sighted children, z scores of 6MWT results in patients with CLN3 disease and control cohort individuals were calculated. 6MWT results were correlated with age-including multilevel modeling analysis allowing assessment of imbalanced repeated measurements-and with Unified Batten Disease Rating Scale (UBDRS) scores. Results In CLN3 disease, 6MWT scores were already impaired from first testing near diagnosis (mean z scores of -3.6 and -4.7 at 7 and 8 years of age, respectively). Afterwards, 6MWT scores continuously declined with age (r = -0.64, p <0.0001) and with increasing UBDRS scores (r = -0.60, p = 0.0001), confirming correlation with disease progression. The decrease was more pronounced at a later age, as shown by the nonlinear multilevel model for 6MWT results in CLN3 disease (y = 409.18 - [0.52 x age(2)]). In contrast, an upward trend of 6MWT scores with age was observed in the control cohort with isolated visual impairment (r = 0.56; p = 0.04) similar to healthy, sighted children. The control cohort with additional neurologic impairments displayed a slightly decreased 6MWT walking distance independent of age. Conclusions The 6MWT unveils early onset of motor decline in CLN3 disease

HDL Particle Size Is a Critical Determinant of ABCA1-Mediated Macrophage Cellular Cholesterol Export

International audienceRationale: High-density lipoprotein (HDL) is a heterogeneous population of particles. Differences in the capacities of HDL subfractions to remove cellular cholesterol may explain variable correlations between HDL-cholesterol and cardiovascular risk and inform future targets for HDL-related therapies. The ATP binding cassette transporter A1 (ABCA1) facilitates cholesterol efflux to lipid-free apolipoprotein A-I, but the majority of apolipoprotein A-I in the circulation is transported in a lipidated state and ABCA1-dependent efflux to individual HDL subfractions has not been systematically studied. Objective: Our aims were to determine which HDL particle subfractions are most efficient in mediating cellular cholesterol efflux from foam cell macrophages and to identify the cellular cholesterol transporters involved in this process. Methods and Results: We used reconstituted HDL particles of defined size and composition, isolated subfractions of human plasma HDL, cell lines stably expressing ABCA1 or ABCG1, and both mouse and human macrophages in which ABCA1 or ABCG1 expression was deleted. We show that ABCA1 is the major mediator of macrophage cholesterol efflux to HDL, demonstrating most marked efficiency with small, dense HDL subfractions (HDL3b and HDL3c). ABCG1 has a lesser role in cholesterol efflux and a negligible role in efflux to HDL3b and HDL3c subfractions. Conclusions: Small, dense HDL subfractions are the most efficient mediators of cholesterol efflux, and ABCA1 mediates cholesterol efflux to small dense HDL and to lipid-free apolipoprotein A-I. HDL-directed therapies should target increasing the concentrations or the cholesterol efflux capacity of small, dense HDL species in vivo