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In a pattern of horizontal lines containing ± 45° zigzagging phase-shifted strips, vivid illusory motion is perceived when the pattern is translated up or down at a moderate speed. Two forms of illusory motion are seen: [i] a motion “racing” along the diagonal interface between the strips and [ii] lateral (sideways) motion of the strip sections. We found the relative salience of these two illusory motions to be strongly influenced by the vertical spacing and length of the line gratings, and the period length of the zigzag strips. Both illusory motions are abolished when the abutting strips are interleaved, separated by a gap or when a real line is superimposed at the interface. Illusory motion is also severely weakened when equiluminant colored grating lines are used. Illusory motion perception is fully restored at < 20% luminance contrast. Using adaptation, we find that line-ends alone are insufficient for illusory motion perception, and that both physical carrier motion and line orientation are required. We finally test a classical spatiotemporal energy model of V1 cells that exhibit direction tuning changes that are consistent with the direction of illusory motion. Taking this data together, we constructed a new visual illusion and surmise its origin to interactions of spatial and temporal energy of the lines and line-ends preferentially driving the magnocellular pathway.

The precise risk/benefit of thienopyridine pretreatment and the optimal dosage and timing of a thienopyridine loading dose (LD) for patients presenting with non–ST-segment elevation (NSTE) acute coronary syndromes are still being debated. Prasugrel, a novel thienopyridine, is an appropriate drug to address this issue as it provides predictably high and rapid inhibition of platelet aggregation. ACCOAST is a phase 3, multicenter, parallel-group, double-blind, and event-driven study designed to compare 2 prasugrel LD schedules in patients with NSTE myocardial infarction who are scheduled for coronary angiography/percutaneous coronary intervention (PCI). Approximately 4,100 patients will be randomly assigned to an initial LD of 30 mg of prasugrel after the diagnosis followed by coronary angiography with an additional dose of 30 mg of prasugrel given at the time of PCI (pretreatment) or an LD of 60 mg of prasugrel given to patients undergoing PCI at the time of the procedure (non-pretreatment). All patients undergoing PCI will receive 5 or 10 mg of prasugrel daily. The primary objective is to test the hypothesis that prasugrel pretreatment is superior to prasugrel non-pretreatment as measured by a reduction in the composite end point of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor bailout through 7 days from randomization. Key safety end points include TIMI (Thrombolysis In Myocardial Infarction) major and minor bleeding risks. The ACCOAST study will provide important evidence with regard to the benefits and risks of prasugrel pretreatment compared with administration of prasugrel at the time of PCI in patients with NSTE myocardial infarction.

Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or β (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period. Interim data from a clinical trial of mRNA-3927—an mRNA therapeutic for propionic acidaemia—provide early indications of the safety and efficacy of the treatment, and suggest that this approach might be applicable to other rare diseases.

The physiological blind spot, corresponding to the optic disk in the retina, is a relatively large (6 × 8°) area in the visual field that receives no retinal input. However, we rarely notice the existence of it in daily life. This is because the blind spot fills in with the brightness, color, texture, and motion of the surround. The study of filling-in enables us to better understand the creative nature of the visual system, which generates perceptual information where there is none. Is there any retinotopic rule in the color filling-in of the blind spot? To find out, we used mono-colored and bi-colored annuli hugging the boundary of the blind spot. We found that mono-colored annuli filled in the blind spot uniformly. By contrast, bi-colored annuli, where one half had a given color, while the other half had a different one, filled in the blind spot asymmetrically. Specifically, the color surrounding the nasal half typically filled in about 75% of the blind spot area, whereas the color surrounding the temporal half filled in only about 25%. This asymmetry was dependent on the relative size of the half rings, but not the two colors used, and was absent when the bi-colored annulus was rotated by 90°. Here, the two colors on the upper and lower sides of the blind spot filled in the enclosed area equally. These results suggest that the strength of filling-in decreases with distance from the fovea consistent with the decrease of the cortical magnification factor.

Numerals, i.e., semantic expressions of numbers, enable us to have an exact representation of the amount of things. Visual processing of numerals plays an indispensable role in the recognition and interpretation of numbers. Here, we investigate how visual information from numerals is processed to achieve semantic understanding. We first found that partial occlusion of some digital numerals introduces bistable interpretations. Next, by using the visual adaptation method, we investigated the origin of this bistability in human participants. We showed that adaptation to digital and normal Arabic numerals, as well as homologous shapes, but not Chinese numerals, biases the interpretation of a partially occluded digital numeral. We suggest that this bistable interpretation is driven by intermediate shape processing stages of vision, i.e., by features more complex than local visual orientations but more basic than the abstract concepts of numerals.

Randomized controlled trials are considered the gold standard to evaluate the treatment effect (estimand) for efficacy and safety. According to the recent International Council on Harmonisation (ICH)-E9 addendum (R1), intercurrent events (ICEs) need to be considered when defining an estimand, and principal stratum is one of the five strategies to handle ICEs. Qu et al. (2020, Statistics in Biopharmaceutical Research 12:1-18) proposed estimators for the adherer average causal effect (AdACE) for estimating the treatment difference for those who adhere to one or both treatments based on the causal-inference framework, and demonstrated the consistency of those estimators; however, this method requires complex custom programming related to high-dimensional numeric integrations. In this article, we implemented the AdACE estimators using multiple imputation (MI) and constructs CI through bootstrapping. A simulation study showed that the MI-based estimators provided consistent estimators with the nominal coverage probabilities of CIs for the treatment difference for the adherent populations of interest. As an illustrative example, the new method was applied to data from a real clinical trial comparing 2 types of basal insulin for patients with type 1 diabetes.

Chapter I. In 1994, generalized estimating equations approach (GEE) was extended by Lipsitz, Kim and Zhao to fit the proportional odds model for analyzing repeated (or clustered) ordinal categorical data. However, few methods exist to assess the goodness of fit (GOF) of the fitted models. Four U statistics were proposed in this study to do the GOF test and their performances were evaluated with respect to type I error rates and powers for detecting various model departures by simulation studies and an example illustration. We also compared the proposed U statistics with a Kappa-like classification statistic. Simulation studies show that the proposed U statistics have no obvious difference with each other and perform better than Kappa like classification statistic. All of U statistics provide correct type I error rates very close to the nominal alpha levels and appropriate powers to detect the omission of a quadratic term or an interaction, or the violation of proportional odds assumption. Chapter II. A time series model was fitted to the pollen concentration data collected at Greater Cincinnati area for Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). A traditional time series analysis and temporal variogram approach were applied to the regularly spaced databases (collected in 2003) and irregularly spaced ones (collected in 2002), respectively. The aim was to evaluate the effect of the sampling frequency on the sampling precision in terms of inverse of standard error of the overall level of mean value across time. The presence of high autocorrelation in the data was confirmed and indicated some degree of temporal redundancy in the pollen concentration data. Therefore, it was suggested that sampling frequency could be reduced from once a day to once every several days without a major loss of sampling precision of the grand mean over time. Considering the trade-offs between sampling frequency and the possibility of sampling bias increasing with larger sampling interval, we recommend that the sampling interval should take values from 3 to 5 days for the pollen monitoring program, if the goal is to track the long-term average.