Efficacy and safety of once-monthly Risperidone ISM ® in schizophrenic patients with an acute exacerbation

Funding: This study was funded by Laboratorios Farmacéuticos Rovi, S.A. Madrid, Spain. It was supported also in part by a grant from Center for the Development of Industrial Technology (Expedient No. IDI-20160109).To evaluate the efficacy and safety of Risperidone ISM ® against placebo in patients with acute exacerbation of schizophrenia. A multicenter, randomized, double-blind, placebo-controlled study was conducted between June 2017 and December 2018 (NCT03160521). Eligible patients received once-monthly intramuscular injections of Risperidone ISM ® (75 or 100 mg) or placebo for 12 weeks. The primary efficacy outcome was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 12. The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Altogether, 438 patients were randomized (1:1:1) and 390 included in the modified ITT efficacy set. The PANSS total score (mean difference, 95% CI) improved significantly from baseline to day 85 with Risperidone ISM ® 75 and 100 mg, with placebo-adjusted differences of −13.0 (95% CI, −17.3 to −8.8); (p < 0.0001), and −13.3 (−17.6 to −8.9); (p < 0.0001), respectively. Significantly improved mean changes were also obtained for CGI-S score from baseline to day 85 for both doses of Risperidone ISM ® compared with placebo −0.7 (−1.0 to −0.5); p < 0.0001, for both doses. The statistically significant improvement for both efficacy outcomes were observed as early as 8 days after first injection. The most frequently reported treatment-emergent adverse events were increased blood prolactin (7.8%), headache (7.3%), hyperprolactinemia (5%), and weight increase (4.8%). Neither new nor unexpected relevant safety information was recorded. Risperidone ISM ® provided rapid and progressive reduction of symptoms in patients with acutely exacerbated schizophrenia without need of oral risperidone supplementation or loading doses. Both doses were safe and well tolerated

C-S-H Pore Size Characterization Via a Combined Nuclear Magnetic Resonance (NMR)-Scanning Electron Microscopy (SEM) Surface Relaxivity Calibration.

A new method for the nuclear magnetic resonance (NMR) surface relaxivity calibration in hydrated cement samples is proposed. This method relies on a combined analysis of 28-d hydrated tricalcium silicate samples by scanning electron microscopy (SEM) image analysis and 1H-time-domain (TD)-NMR relaxometry. Pore surface and volume data for interhydrate pores are obtained from high resolution SEM images on surfaces obtained by argon broad ion beam sectioning. These data are combined with T2 relaxation times from 1H-TD-NMR to calculate the systems surface relaxivity according to the fast exchange model of relaxation. This new method is compared to an alternative method that employs sequential drying to calibrate the systems surface relaxivity

The Costs of Paying Overt and Covert Attention Assessed With Pupillometry

Attention can be shifted with or without an accompanying saccade (i.e., overtly or covertly, respectively). Thus far, it is unknown how cognitively costly these shifts are, yet such quantification is necessary to understand how and when attention is deployed overtly or covertly. In our first experiment (N = 24 adults), we used pupillometry to show that shifting attention overtly is more costly than shifting attention covertly, likely because planning saccades is more complex. We pose that these differential costs will, in part, determine whether attention is shifted overtly or covertly in a given context. A subsequent experiment (N = 24 adults) showed that relatively complex oblique saccades are more costly than relatively simple saccades in horizontal or vertical directions. This provides a possible explanation for the cardinal-direction bias of saccades. The utility of a cost perspective as presented here is vital to furthering our understanding of the multitude of decisions involved in processing and interacting with the external world efficiently

The Intensity of Internal and External Attention Assessed with Pupillometry

Not only is visual attention shifted to objects in the external world, attention can also be directed to objects in memory. We have recently shown that pupil size indexes how strongly items are attended externally, which was reflected in more precise encoding into visual working memory. Using a retro-cuing paradigm, we here replicated this finding by showing that stronger pupil constrictions during encoding were reflective of the depth of encoding. Importantly, we extend this previous work by showing that pupil size also revealed the intensity of internal attention toward content stored in visual working memory. Specifically, pupil dilation during the prioritization of one among multiple internally stored representations predicted the precision of the prioritized item. Furthermore, the dynamics of the pupillary responses revealed that the intensity of internal and external attention independently determined the precision of internalized visual representations. Our results show that both internal and external attention are not all-or-none processes, but should rather be thought of as continuous resources that can be deployed at varying intensities. The employed pupillometric approach allows to unravel the intricate interplay between internal and external attention and their effects on visual working memory

Uncovering the (un)attended: Pupil light responses index persistent biases of spatial attention in neglect

Visuospatial neglect is a frequent and disabling disorder, mostly after stroke, that presents in impaired awareness to stimuli on one side of space. Neglect causes disability and functional dependence, even long after the injury. Improving measurements of the core attentional deficit might hold the key for better understanding of the condition and development of treatment. We present a rapid, pupillometry-based method that assesses automatic biases in (covert) attention, without requiring behavioral responses. We exploit the phenomenon that pupil light responses scale with the degree of covert attention to stimuli, and thereby reveal what draws (no) attention. Participants with left-sided neglect after right-sided lesions following stroke (n = 5), participants with hemianopia/quadrantanopia following stroke (n = 11), and controls (n = 22) were presented with two vertical bars, one of which was white and one of which was black, while fixating the center. We varied which brightness was left and right, respectively across trials. In line with the hypotheses, participants with neglect demonstrated biased pupil light responses to the brightness on the right side. Participants with hemianopia showed similar biases to intact parts of the visual field, whilst controls exhibited no bias. Together, this demonstrates that the pupil light response can reveal not only visual, but also attentional deficits. Strikingly, our pupillometry-based bias estimates were not in agreement with neuropsychological paper-and-pencil assessments conducted on the same day, but were with those administered in an earlier phase post-stroke. Potentially, we pick up on persistent biases in the covert attentional system that participants increasingly compensate for in classical neuropsychological tasks and everyday life. The here proposed method may not only find clinical application, but also advance theory and aid the development of successful restoration therapies by introducing a precise, longitudinally valid, and objective measurement that might not be affected by compensation

Differential aspects of attention predict the depth of visual working memory encoding: Evidence from pupillometry

What determines how much one encodes into visual working memory? Traditionally, encoding depth is considered to be indexed by spatiotemporal properties of gaze, such as gaze position and dwell time. Although these properties inform about where and how long one looks, they do not necessarily inform about the current arousal state or how strongly attention is deployed to facilitate encoding. Here, we found that two types of pupillary dynamics predict how much information is encoded during a copy task. The task involved encoding a spatial pattern of multiple items for later reproduction. Results showed that smaller baseline pupil sizes preceding and stronger pupil orienting responses during encoding predicted that more information was encoded into visual working memory. Additionally, we show that pupil size reflects not only how much but also how precisely material is encoded. We argue that a smaller pupil size preceding encoding is related to increased exploitation, whereas larger pupil constrictions signal stronger attentional (re)orienting to the to-be-encoded pattern. Our findings support the notion that the depth of visual working memory encoding is the integrative outcome of differential aspects of attention: how alert one is, how much attention one deploys, and how long it is deployed. Together, these factors determine how much information is encoded into visual working memory