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Funder: Unitaid, Repurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase I trial in healthy adult participants was undertaken with high-dose nitazoxanide. Participants received 1,500 mg nitazoxanide orally twice-daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose, and schedule. Intensive pharmacokinetic (PK) sampling was undertaken day 1 and 5 with minimum concentration (Cmin ) sampling on days 3 and 7. Fourteen healthy participants were enrolled between February 18 and May 11, 2021. All 14 doses were completed by 10 of 14 participants. Nitazoxanide was safe and with no significant adverse events. Moderate gastrointestinal disturbance (loose stools or diarrhea) occurred in 8 participants (57.1%), with urine and sclera discoloration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self-limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on the first dose and maintained throughout. Nitazoxanide administered at 1,500 mg b.i.d. with food was safe with acceptable tolerability a phase Ib/IIa study is now being initiated in patients with COVID-19.

Introduction Technological advances have introduced three-dimensional (3-D) printing as an option for creating tactile maps for people with visual impairments (that is, those who are blind or have low vision), diversifying the types of map products that are available. At the same time, it presents a challenge to map makers to implement designs across multiple production methods. We evaluated map symbols to determine their discriminability across three different materials: microcapsule paper, 3-D printer plastic, and embossed paper. Methods In a single session lasting less than 90 minutes, participants completed a matching task and provided informal feedback regarding their preferences. We measured speed and accuracy to establish discriminability of map symbols on each of the materials. Eighteen participants were recruited from a referred sample among attendees at the American Council of the Blind annual convention in 2013. Results Response times were significantly different across the three materials (p < 0.001). Without sacrificing accuracy, response times were faster for the 3-D printed graphics than for either the microcapsule paper (p < 0.001) or the embossed paper (p < 0.001). User preference was divided across the three materials. Some people disliked the “sharp” corners of the 3-D printed symbols, while others preferred their “crisp” edges. Discussion Our results demonstrate faster discriminability of a set of tactile symbols produced on a 3-D printer compared to those same symbols printed on microcapsule paper, the material for which the symbols were originally designed. Participant feedback reflected preferences both in favor of and against reading symbols produced on the 3-D printer. Implications for practitioners This article discusses the functional equivalence of tactile symbols produced across multiple production technologies. It addresses two considerations when using 3-D printing to make tactile maps: preparing digital files for printing and the printing work flow. Digital files ready for printing on each of the three materials are available for download (Brittell, Lobben, & Lawrence 2016).

There is a long-standing debate on the influence of physiological signals on social behavior. Recent studies suggested that heart rate variability (HRV) may be a marker of social cognitive processes. However, this evidence is preliminary and limited to laboratory studies. In this study, 25 participants were assessed with a social cognition battery and asked to wear a wearable device measuring HRV for 6 consecutive days. The results showed that reduced HRV correlated with higher hostility attribution bias. However, no relationship was found between HRV and other social cognitive measures including facial emotion recognition, theory of mind or emotional intelligence. These results suggest that HRV may be linked to specific social cognitive processes requiring online emotional processing, in particular those related to social threat. These findings are discussed in the context of the neurovisceral integration model.

Introduction: Research suggests that people with schizophrenia have autonomic dysfunctions. These have been linked to functioning problems, symptoms and considered a risk factor for illness chronicity. The aim of this study is to introduce a new Mobile Health (mHealth) method using wearable technology to assessing autonomic activity in people's everyday life. We aim to evaluate the new method acceptability and characterise the association between schizophrenia illness features and autonomic abnormalities. Method: Thirty participants with schizophrenia and 25 controls were asked to wear a mHealth device measuring autonomic activity and movements during their normal everyday life. Measures of device use acceptability were collected from all participants. Participants with schizophrenia were also assessed for symptoms and functioning levels. Measures of heart rate variability (HRV), electrodermal activity (EDA) and movement were collected by the device and groups were compared. Correlation between physiological measures, functioning, symptoms and medication levels were assessed in people with schizophrenia. Results: The mHealth device method proved to be acceptable and produced reliable measures of autonomic activity and behaviour. Compared to controls, people with schizophrenia showed lower levels of HRV, movement and functioning. In people with schizophrenia illness severity, particularly positive symptoms, was associated with parasympathetic deregulation. Conclusions: Autonomic abnormalities can be detected using wearable technology from people's everyday life. These are in line with previous research and support the notion that autonomic deregulation are relevant illness features for mental and physical health in schizophrenia. This method may be developed as a monitoring system for well-being and relapse prevention.

Background: People with a diagnosis of schizophrenia have significant social and functional difficulties. Social cognition was found to influences these outcomes and in recent years interventions targeting this domain were developed. This paper reviews the existing literature on social cognition interventions for people with a diagnosis of schizophrenia focussing on: i) comparing focussed (i.e. targeting only one social cognitive domain) and global interventions and ii) studies methodological quality. Method: Systematic search was conducted on PubMed and PsycInfo. Studies were included if they were randomised control trials, participants had a diagnosis of schizophrenia or schizoaffective disorder, and the intervention targeted at least one out of four social cognition domains (i.e. theory of mind, affect recognition, social perception and attribution bias). All papers were assessed for methodological quality. Information on the intervention, control condition, study methodology and the main findings from each study were extracted and critically summarised. Results: Data from 32 studies fulfilled the inclusion criteria, considering a total of 1440 participants. Taking part in social cognition interventions produced significant improvements in theory of mind and affect recognition compared to both passive and active control conditions. Results were less clear for social perception and attributional bias. Focussed and global interventions had similar results on outcomes. Overall study methodological quality was modest. There was very limited evidence showing that social cognitive intervention result in functional outcome improvement. Conclusions: The evidence considered suggests that social cognition interventions may be a valuable approach for people with a diagnosis of schizophrenia. However, evidence quality is limited by measure heterogeneity, modest study methodology and short follow-up periods. The findings point to a number of recommendations for future research, including measurement standardisation, appropriately powered studies and investigation of the impact of social cognition improvements on functioning problems.

In the past decade, the use of functional magnetic resonance imaging (fMRI) has grown, both in the number of studies published and in the number of disciplines finding application for functional brain research facilitated by this data-gathering method. A review of fMRI research in perceptual grouping and figure/ground and in visual search and attention is of interest in the effort to understand the human use of maps. These studies provide physiological evidence that can at least tentatively be interpreted as supporting principles in map design. Although they are not specifically cartographic, these studies dovetail with some of the human-user research in cartography. The question of how these studies of very specific phenomena, using very limited graphics, fit the overall picture of map use is an open one. At the very least, they provide an additional window into the processes of map use.