Dynamic in-flight shifts of working memory resources across saccades

Little is known about how memory resources are allocated in natural vision across sequential eye movements and fixations, as people actively extract information from the visual environment. Here, we used gaze-contingent eye tracking to examine how such resources are dynamically reallocated from old to new information entering working memory. As participants looked sequentially at items, we interrupted the process at different times by extinguishing the display as a saccade was initiated. After a brief interval, participants were probed on one of the items that had been presented. Paradoxically, across all experiments, the final (unfixated) saccade target was recalled more precisely when more items had previously been fixated, that is, with longer rather than shorter saccade sequences. This result is difficult to explain on current models of working memory because recall error, even for the final item, is typically higher as memory load increases. The findings could however be accounted for by a model that describes how resources are dynamically reallocated on a moment-by-moment basis. During each saccade, the target is encoded by consuming a proportion of currently available resources from a limited working memory, as well as by reallocating resources away from previously encoded items. These findings reveal how working memory resources are shifted across memoranda in active vision. Public Significance Statement We continuously make rapid eye movements called saccades to inspect the world around us. A short-term store is needed to hold this information temporarily, to build an internal representation of the visual scene, or guide our actions within the visual environment. It is well established that visual short-term memory is highly limited in capacity, which confronts us with a challenge: When storing information across saccade sequences, how do we reallocate memory resources to new incoming information? Here, we show that resources are dynamically reallocated away from previously fixated items stored in memory to make room for the new saccade target. A large amount of information is stored about this target, even before the saccade is made. Our results suggest a mechanism of how limited memory resources are dynamically allocated in order to support our ability to remember information from the visual scene

Adaptive working memory training does not produce transfer effects in cognition and neuroimaging

Despite growing interest in cognitive interventions from academia and industry, it remains unclear if working memory (WM) training, one of the most popular cognitive interventions, produces transfer effects. Transfer effects are training-induced gains in performance in untrained cognitive tasks, while practice effects are improvements in trained task. The goal of this study was to evaluate potential transfer effects by comprehensive cognitive testing and neuroimaging. In this prospective, randomized-controlled, and single-blind study, we administered an 8-week n-back training to 55 healthy middle-aged (50–64 years) participants. State-of-the-art multimodal neuroimaging was used to examine potential anatomic and functional changes. Relative to control subjects, who performed non-adaptive WM training, no near or far transfer effects were detected in experimental subjects, who performed adaptive WM training. Equivalently, no training-related changes were observed in white matter integrity, amplitude of low frequency fluctuations, glucose metabolism, functional and metabolic connectivity. Exploratory within-group comparisons revealed some gains in transfer tasks, which, however, cannot be attributed to an increased WM capacity. In conclusion, WM training produces transfer effects neither at the cognitive level nor in terms of neural structure or function. These results speak against a common view that training-related gains reflect an increase in underlying WM capacity. Instead, the presently observed practice effects may be a result of optimized task processing strategies, which do not necessarily engage neural plasticity

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. Funding Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Sustainability criteria for the design of stormwater drainage systems for the 21st century

This paper proposes a new approach to the design of stormwater drainage using sustainability indicators to provide a total measure of system performance rather than looking only at design criteria to meet a minimum level of service. This methodology can apply to all aspects of sustainability, but this paper focuses on indicators to measure the hydraulic performance and treatment effectiveness of stormwater drainage systems. The paper outlines the methodology, the relevance of the indicators and the tools developed. The paper then discusses the application of the methodology and results for the Elvetham Heath drainage system. This work was carried out as part of the EPSRC funded WaND (Water cycle management for New Developments) project, which completed in December 2007

Sustainability measures applied to an urban stormwater drainage system

This paper describes the application of sustainability measures of hydraulic performance and water quality protection to a real-life urban stormwater drainage system. This includes details of the practicalities of applying sustainability measures to drainage designs, a summary of the InfoWorks CS hydraulic model results, and a discussion of how these results were applied using tools developed as part of the WaND project

International approaches to the hydraulic control of surface water runoff in mitigating flood and environmental risks

This paper compares and contrasts a number of international approaches to the hydraulic control of surface water runoff from new development and redevelopment, known as sustainable drainage systems (SuDS) or low impact development (LID). The paper provides a commentary on the progress and current status of national standards for SuDS in the UK to control the frequency, flow rate and volume of runoff from both frequent and extreme rainfall events, and the best practice design criteria presented in the revised UK CIRIA SuDS Manual, published in November 2015. The paper then compares these design criteria and standards with those developed and applied in China, USA, France and Germany and also looks at the drivers behind their development. The benefits of these different approaches are assessed in the context of flood risk mitigation, climate resilience and wider environmental protection objectives, including water quality, morphology and ecology. The paper also reviews the design approaches promoted by the new SuDS Manual and internationally for delivering additional benefits for urban spaces (such as recreation, visual character, education and economic growth) through multi-functional urban design

Movement cues aid face recognition in developmental prosopagnosia

Objective: Seeing a face in motion can improve face recognition in the general population, and studies of face matching indicate that people with face recognition difficulties (developmental prosopagnosia; DP) may be able to use movement cues as a supplementary strategy to help them process faces. However, the use of facial movement cues in DP has not been examined in the context of familiar face recognition. This study examined whether people with DP were better at recognizing famous faces presented in motion, compared to static. Methods: Nine participants with DP and 14 age-matched controls completed a famous face recognition task. Each face was presented twice across 2 blocks: once in motion and once as a still image. Discriminability (A) was calculated for each block. Results: Participants with DP showed a significant movement advantage overall. This was driven by a movement advantage in the first block, but not in the second block. Participants with DP were significantly worse than controls at identifying faces from static images, but there was no difference between those with DP and controls for moving images. Conclusions: Seeing a familiar face in motion can improve face recognition in people with DP, at least in some circumstances. The mechanisms behind this effect are unclear, but these results suggest that some people with DP are able to learn and recognize patterns of facial motion, and movement can act as a useful cue when face recognition is impaired

Oxytocin increases bias, but not accuracy, in face recognition line-ups

© The Author (2014). Previous work indicates that intranasal inhalation of oxytocin improves face recognition skills, raising the possibility that it may be used in security settings. However, it is unclear whether oxytocin directly acts upon the core face-processing system itself or indirectly improves face recognition via affective or social salience mechanisms. In a double-blind procedure, 60 participants received either an oxytocin or placebo nasal spray before completing the One-in-Ten task-a standardized test of unfamiliar face recognition containing target-present and target-absent line-ups. Participants in the oxytocin condition outperformed those in the placebo condition on target-present trials, yet were more likely to make false-positive errors on target-absent trials. Signal detection analyses indicated that oxytocin induced a more liberal response bias, rather than increasing accuracy per se. These findings support a social salience account of the effects of oxytocin on face recognition and indicate that oxytocin may impede face recognition in certain scenarios

Development and application of a framework to understand the available capacity in the UK’s drainage systems

The vision of the 21st Century Drainage Programme is to enable the UK water industry, in partnership with the UK’s governments and regulators, to take action now that will ensure the resilience and sustainability of our drainage infrastructure in the future. As part of this Programme, Workstream 2 has been focused on understanding the available capacity in the UK’s foul and combined drainage systems to accommodate present-day flows and flows expected in the future. The first phase of this work resulted in The 21st Century Drainage Programme Capacity Assessment Framework - a consistent, transparent and high-level approach to assessing available capacity and investment needed in the long term. This paper describes the approach adopted by the Framework (completed in April 2017) for assessing performance and investment (present day, future and future with intervention), the metrics used by the assessment and how this information is to be visualised. This paper also introduces the second phase of work, which is currently underway, supporting all 12 of the UK’s sewerage undertakers as they embed the Framework into their organisations. This includes the development of a first draft National Picture of present day drainage capacity, due for publication in late November 2017