Longitudinal Network Changes and Conversion to Cognitive Impairment in Multiple Sclerosis

OBJECTIVE: To characterize functional network changes related to conversion to cognitive impairment in a large sample of MS patients over a period of 5 years. METHODS: 227 MS patients and 59 healthy controls (HCs) of the Amsterdam MS cohort underwent neuropsychological testing and resting-state fMRI at two time points (time-interval 4.9±0.9 years). At both baseline and follow-up, patients were categorized as cognitively preserved (CP, N=123), mildly impaired (MCI, Z<-1.5 on ≥2 cognitive tests, N=32) or impaired (CI, Z<-2 on ≥2 tests, N=72) and longitudinal conversion between groups was determined. Network function was quantified using eigenvector centrality, a measure of regional network importance, which was computed for individual resting-state networks at both time-points. RESULTS: Over time, 18.9% of patients converted to a worse phenotype; 22/123 CP patients (17.9%) converted from CP to MCI, 10/123 from CP to CI (8.1%) and 12/32 MCI patients converted to CI (37.5%). At baseline, DMN centrality was higher in CI compared to controls (P=.05). Longitudinally, ventral attention network (VAN) importance increased in CP, driven by stable CP and CP-to-MCI converters (P<.05). CONCLUSIONS: Of all patients, 19% worsened in their cognitive status over five years. Conversion from intact cognition to impairment is related to an initial disturbed functioning of the VAN, then shifting towards DMN dysfunction in CI. As the VAN normally relays information to the DMN, these results could indicate that in MS, normal processes crucial for maintaining overall network stability are progressively disrupted as patients clinically progress

Performance of non-uniform tidal turbine arrays in uniform flow

Theoretical models suggest that in order to maximise their collective power out put, tidal turbines should be arranged in a single cross-stream row and optimally spaced to exploit local blockage effects. However, because it is assumed that the turbines within these arrays are identical, such models do not consider the possibility of enhanced power production through the exploitation of spanwise variations in local blockage and resistance. In this paper, we use depth-averaged numerical simulations to investigate whether the performance of a tidal turbine array can be further enhanced by varying solely the local blockage, solely the local resistance, or both local blockage and resistance together, across the array width. Our results suggest that for an initially uniform flow field, the optimal tidal turbine array is also uniform, that is to say that it comprises turbines of equal size, spacing, and resistance. This finding is encouraging because it is more cost-effective and much simpler to design each turbine to be the same and to operate in the same way. Together with earlier findings, these results also suggest a more general, and perhaps unsurprising, conclusion that tidal turbine arrays perform best when designed to match site-specific natural flow conditions

Eta Carinae -- Physics of the Inner Ejecta

Eta Carinae's inner ejecta are dominated observationally by the bright Weigelt blobs and their famously rich spectra of nebular emission and absorption lines. They are dense (n_e ~ 10^7 to 10^8 cm^-3), warm (T_e ~ 6000 to 7000 K) and slow moving (~40 km/s) condensations of mostly neutral (H^0) gas. Located within 1000 AU of the central star, they contain heavily CNO-processed material that was ejected from the star about a century ago. Outside the blobs, the inner ejecta include absorption-line clouds with similar conditions, plus emission-line gas that has generally lower densities and a wider range of speeds (reaching a few hundred km/s) compared to the blobs. The blobs appear to contain a negligible amount of dust and have a nearly dust-free view of the central source, but our view across the inner ejecta is severely affected by uncertain amounts of dust having a patchy distribution in the foreground. Emission lines from the inner ejecta are powered by photoionization and fluorescent processes. The variable nature of this emission, occurring in a 5.54 yr event cycle, requires specific changes to the incident flux that hold important clues to the nature of the central object.Comment: This is Chapter 5 in a book entitled: Eta Carinae and the Supernova Impostors, Kris Davidson and Roberta M. Humphreys, editors Springe

Higher-Order optimality conditions for set-valued optimization

2007-2008 > Academic research: refereed > Publication in refereed journa

Methods designed for the identification and characterization of in vitro and in vivo chromatin assembly mutants in Saccharomyces cerevisiae

Assembly of DNA into chromatin allows for the formation of a barrier that protects naked DNA from protein and chemical agents geared to degrade or metabolize DNA. Chromatin assembly occurs whenever a length of DNA becomes exposed to the cellular elements, whether during DNA synthesis or repair. This report describes tools to study chromatin assembly in the model system Saccharomyces cerevisiae. Modifications to an in vitro chromatin assembly assay are described that allowed a brute force screen of temperature sensitive (ts) yeast strains in order to identify chromatin assembly defective extracts. This screen yielded mutations in genes encoding two ubiquitin protein ligases (E3s): RSP5, and a subunit of the Anaphase Promoting Complex (APC), APC5. Additional modifications are described that allow for a rapid analysis and an in vivo characterization of yeast chromatin assembly mutants, as well as any other mutant of interest. Our analysis suggests that the in vitro and in vivo chromatin assembly assays are responsive to different cellular signals, including cell cycle cues that involve different molecular networks

Impact of Antioxidant Therapy on Natural Pregnancy Outcomes and Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS. Materials and methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines. Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair. Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful

Understanding Social Resilience in the Maine Lobster Industry

The Maine lobster Homarus americanus fishery is considered one of the most successful fisheries in the world due in part to its unique comanagement system, the conservation ethic of the harvesters, and the ability of the industry to respond to crises and solve collective-action problems. However, recent threats raise the question whether the industry will be able to respond to future threats as successfully as it has to ones in the past or whether it is now less resilient and can no longer adequately respond to threats. Through ethnographic research and oral histories with fishermen, we examined the current level of social resilience in the lobster fishery. We concentrated on recent threats to the industry and the ways in which it has responded to them, focusing on three situations: a price drop beginning in 2008, a recovery in 2010–2011, and a second collapse of prices in 2012. In addition, we considered other environmental and regulatory concerns identified by fishermen. We found that the industry is not responding effectively to recent threats and identified factors that might explain the level of social resilience in the fishery