Cardiovascular disease is more common in patients with chronic kidney disease (CKD), and traditional risk factors do not adequately predict those at risk for cardiovascular (CV) events. Recent evidence suggests elevated trimethylamine N-oxide (TMAO), created by gut microflora from dietary L-carnitine and choline, is associated with CV events. We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort, a Canada-wide observational study with prospective 3-year follow-up of adjudicated CV events. Baseline samples were obtained for 2529 CKD patients. TMAO, choline, and L-carnitine levels were measured using tandem mass spectrometry. Baseline median TMAO level was high for the whole cohort (20.41 μM; interquartile range [IQR]: 12.82-32.70 μM). TMAO was independently associated with CV events (hazard ratio 1.23; 95% confidence interval: 1.06-1.42 / 1 SD lnTMAO) after adjusting for all potential CV risk factors. Those in the highest TMAO quartile had significantly higher risk of CV events (adjusted hazard ratio 1.59; 95% confidence interval: 1.04-2.43; P = 0.0351) in the analysis of recurring ischemic events. Among those with stage 3b CKD (hazard ratio 1.45; 95% confidence interval: 1.12-1.87 / 1 SD lnTMAO), independent of kidney function, TMAO levels identified those at highest risk for events. Our results suggest that TMAO may represent a new potentially modifiable CV risk factor for CKD patients. Further studies are needed to determine sources of variability and if lowering of TMAO reduces CV risk in CKD.
Responding to a target's current (probe trial) location is slower when it appears at a former distractor-occupied position (i.e., ignored-repetition [IR] trial), relative to when it arises at a new location (i.e., control trial). This RT(IR) > RT(Control) inequality defines the spatial negative priming (SNP) effect in latency terms. It is uncertain whether the elevated RT(IR) is due to the inhibition of the distractor-occupied location or to the inhibition of this location's assigned manual response (SNP locus issue). The main aim here was to examine the SNP locus issue. Notably, our SNP design used centrally presented visual events and included having two locations share a common response (many:1 location-to-response mapping) and the use of informative (70 % validity) or uninformative probe-trial response cues. The many:1 mapping trials allowed for the detection of location and response inhibition presence. Results showed that the latter, but not the former, causes inhibitory aftereffects (e.g., SNP) following uninformative response cues. Consistent with this finding, when the informative response cue was valid and was assigned to the many:1 probe response that had just served as the prime distractor response, inhibitory aftereffects were eliminated, when the probe target appeared at the prime distractor position (IR trial) or at a new location (distractor-response repeat trial). Blocked retrieval of stored distractor-processing representations was proposed as the mechanism for inhibitory aftereffect prevention.
Younger (M = 21 years) and older (M = 74 years) adults completed a spatial negative priming (SNP) task where (central) events (i.e., target or distractor) are presented in trial pairs: first the prime and then the probe. Free-choice trials were included (1 location: 2 permissible responses), which allowed us to isolate response inhibition and its consequent inhibitory aftereffects (i.e., current inhibition interferes with later related processing-e.g., SNP). The inhibitory aftereffects associated with the suppression of responses activated by distractor-occupied locations were highly comparable for younger and older adults; including similar SNP effect sizes, a significant tendency to select against former distractor (inhibited) responses (within-hand finger options) on free-choice trials, and latency delays attributable solely to the use of self-selected distractor responses. Aftereffects generated by target-occupied prime trials locations were also the same for both age groups; recently executed target responses were selected for and produced faster responding (within hand). Aftereffects were absent on between-hand free-choice trials and, overall, response selection determinants on free-choice trials matched for older and younger adults.
In location-based tasks, responses related to (prime trial) distractor-occupied locations automatically undergo activation, followed by inhibition, which causes these responses to become execution-resistant (ER). Distractor-response ER takes time to override, delaying target reactions that later require this response (e.g., probe, ignored-repetition trials), causing the spatial negative priming (SNP) phenomenon. We learned in this study that distractor-response ER affords this output a degree of error protection. Specifically, when the probe target appeared at a new location, former (prime) distractor responses were used erroneously significantly less often than their control response counterparts, likely due to their ER feature, which discourages their inappropriate selection (i.e., "ER" provides error protection). This error protection also was evident when a previous distractor response was activated by a distractor on the probe (i.e., distractor-repeat trial). Notably, error protection remained effective over extensive practice, as did SNP size (i.e., ER override time) after an initial decline.
We determine all non-edge-to-edge tilings of the sphere by regular spherical polygons of three or more sides.
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