20 years of crystal hits: progress and promise in ultrahigh-throughput crystallization screening.

Diffraction-based structural methods contribute a large fraction of the biomolecular structural models available, providing a critical understanding of macromolecular architecture. These methods require crystallization of the target molecule, which remains a primary bottleneck in crystal-based structure determination. The National High-Throughput Crystallization Center at Hauptman-Woodward Medical Research Institute has focused on overcoming obstacles to crystallization through a combination of robotics-enabled high-throughput screening and advanced imaging to increase the success of finding crystallization conditions. This paper will describe the lessons learned from over 20 years of operation of our high-throughput crystallization services. The current experimental pipelines, instrumentation, imaging capabilities and software for image viewing and crystal scoring are detailed. New developments in the field and opportunities for further improvements in biomolecular crystallization are reflected on.

The efficacy of the Dyson air purifier on asthma control: A single-center, investigator-led, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Air pollution is associated with poor asthma outcomes. High-efficiency particulate air air purifiers may reduce air pollution and thus improve asthma outcomes. However, the efficacy of such devices for this purpose remains inconclusive. OBJECTIVE: To investigate the effects of reducing the levels of pollutants on asthma outcomes in adults, using a novel Dyson high-efficiency particulate air air purifier. METHODS: In a single-center, double-blinded, randomized controlled trial, participants (N = 50) were randomized at a 1:1 ratio to active filters (intervention) or to dummy filters (placebo) for a total of 78 weeks. The primary outcomes were the changes in Asthma Control Questionnaire 6 (ACQ6) and Asthma-specific Quality of Life Questionnaire (AQLQ) scores from baseline. The secondary outcomes were changes in indoor air pollution and lung function measurements. The coronavirus disease 2019 pandemic limited spirometry measurements to 2 time points and assessment of fractional exhaled nitric oxide and bronchial hyperresponsiveness to baseline only. RESULTS: Air pollutant levels were significantly lower in the intervention group compared with the placebo group (P = .0003). Both groups had a significant improvement in their ACQ6 and AQLQ. However, there were no significant between-group differences in ACQ6, AQLQ, or spirometry, compared with baseline in multivariable repeated measures models. CONCLUSION: The Dyson air purifier significantly improved air quality. However, there were no significant improvements in asthma control, quality of life, or measures of lung function in the intervention group compared with the control group despite improvements in indoor air quality. Larger, extended studies are required to confirm or refute these findings, especially given that the coronavirus disease 2019 pandemic prevented the procurement of detailed objective data. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04729530; ttps://clinicaltrials.gov/ct2/show/NCT04729530.

Improving Inclusivity in Robotics Design: An Exploration of Methods for Upstream Co-Creation.

Disabled people are often involved in robotics research as potential users of technologies which address specific needs. However, their more generalised lived expertise is not usually included when planning the overall design trajectory of robots for health and social care purposes. This risks losing valuable insight into the lived experience of disabled people, and impinges on their right to be involved in the shaping of their future care. This project draws upon the expertise of an interdisciplinary team to explore methodologies for involving people with disabilities in the early design of care robots in a way that enables incorporation of their broader values, experiences and expectations. We developed a comparative set of focus group workshops using Community Philosophy, LEGO® Serious Play® and Design Thinking to explore how people with a range of different physical impairments used these techniques to envision a "useful robot". The outputs were then workshopped with a group of roboticists and designers to explore how they interacted with the thematic map produced. Through this process, we aimed to understand how people living with disability think robots might improve their lives and consider new ways of bringing the fullness of lived experience into earlier stages of robot design. Secondary aims were to assess whether and how co-creative methodologies might produce actionable information for designers (or why not), and to deepen the exchange of social scientific and technical knowledge about feasible trajectories for robotics in health-social care. Our analysis indicated that using these methods in a sequential process of workshops with disabled people and incorporating engineers and other stakeholders at the Design Thinking stage could potentially produce technologically actionable results to inform follow-on proposals.

Development of advanced oil/water separation technologies to enhance the effectiveness of mechanical oil recovery operations at sea: Potential and challenges.

Mechanical oil recovery (i.e., booming and skimming) is the most common tool for oil spill response. The recovered fluid generated from skimming processes may contain a considerable proportion of water (10 % ~ 70 %). As a result of regulatory prohibition on the discharge of contaminated waters at sea, vessels and/or storage barges must make frequent trips to shore for oil-water waste disposal. This practice can be time- consuming thus reduces the overall efficiency and capacity of oil recovery. One potential solution is on-site oil-water separation and disposal of water fraction at sea. However, currently available decanting processes may have limited oil/water separation capabilities, especially in the presence of oil-water emulsion, which is inevitable in mechanical oil recovery. The decanted water may not meet the discharge standards and cause severe ecotoxicological impacts. This paper therefore comprehensively reviews the principles and progress in oil/water separation, demulsification, and on-site treatment technologies, investigates their applicability on decanting at sea, and discusses the ecotoxicity of decanted water in the marine environment. The outputs provide the fundamental and practical knowledge on decanting and help enhance response effectiveness and consequently reducing the environmental impacts of oil spills.

The Efficacy of the Dyson Air Purifier in Improving Asthma Control: Protocol for a Single-Center, Investigator-Led, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Indoor air quality has been shown to influence asthma control and outcomes. Air purifiers and high-efficiency particulate air filtration devices can improve indoor air quality by reducing the indoor levels of air pollution and allergens. However, the influence of this improved indoor air quality on asthma control remains unclear; hence, randomized controlled trials are needed to further elucidate this phenomenon. OBJECTIVE: This study aims to investigate the effect of reducing the levels of allergens and pollutants in the bedroom and living room through the use of Dyson air purifiers (Dyson Pure Cool) on asthma control. METHODS: This is an 18-month long, investigator-led, randomized, double-blinded, placebo-controlled, single-center trial. Subjects will be randomized in a 1:1 ratio to active or placebo Dyson filters. The primary outcome is the change in the scores of Asthma Control Questionnaire 6 and Asthma-specific Quality of Life Questionnaire from baseline. Secondary outcomes include changes in lung function (forced expiratory volume in one second, forced expiratory volume in one second/forced vital capacity ratio, and midexpiratory flows), peak expiratory flow measurements, airway hyperresponsiveness (assessed by methacholine bronchial challenge), fractional exhaled nitric oxide, and indoor air pollutant levels. The sample size will be 50 subjects, and all subjects will have a confirmed diagnosis of mild persistent to moderate persistent asthma along with an Asthma Control Questionnaire 6 score of >1.5. RESULTS: This study was approved by the West Midlands Research Ethics Committee (18/WM/0277). The study results will be published in peer-reviewed scientific journals; presented at relevant scientific conferences; and shared in plain English with participants in our newsletters, in our clinics, and via the David Hide Asthma and Allergy Research Centre website. Our trial began in September 2019 and is expected to end in August 2021. CONCLUSIONS: This is a double-blinded, placebo-controlled, randomized, investigator-led study to investigate the efficacy of a novel air purifier in improving asthma control in adults. The trial period of 18 months will facilitate the collection of robust data and will therefore generate clear signals. However, this extended trial duration may lead to patient withdrawal. Furthermore, this trial is conducted at a single center and in a location with a homogenous cohort of people, which may affect translatability. Nonetheless, it is hoped that the findings of this trial may help further inform clinicians regarding the utility of this novel device as an adjunct in asthma care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04729530; https://clinicaltrials.gov/ct2/show/NCT04729530. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28624.

Towards an Intelligent Observatory.

The Intelligent Observatory (IO) refers to the vision of the South African Astronomical Observatory (SAAO) to meet the scientific needs of both the South African and international astronomical communities by providing a better and more efficient service. The idea behind the IO is to harmonise the astronomical operations of all the hosted and local astronomical facilities on the Sutherland Plateau. The vision requires both upgrades to some of the telescopes and a re-design of the current Sutherland operations model. The primary science driver, for the IO, is time-domain and transient science.

The Use of a Smartphone App and an Activity Tracker to Promote Physical Activity in the Management of Chronic Obstructive Pulmonary Disease: Randomized Controlled Feasibility Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is highly prevalent and significantly affects the daily functioning of patients. Self-management strategies, including increasing physical activity, can help people with COPD have better health and a better quality of life. Digital mobile health (mHealth) techniques have the potential to aid the delivery of self-management interventions for COPD. We developed an mHealth intervention (Self-Management supported by Assistive, Rehabilitative, and Telehealth technologies-COPD [SMART-COPD]), delivered via a smartphone app and an activity tracker, to help people with COPD maintain (or increase) physical activity after undertaking pulmonary rehabilitation (PR). OBJECTIVE: This study aimed to determine the feasibility and acceptability of using the SMART-COPD intervention for the self-management of physical activity and to explore the feasibility of conducting a future randomized controlled trial (RCT) to investigate its effectiveness. METHODS: We conducted a randomized feasibility study. A total of 30 participants with COPD were randomly allocated to receive the SMART-COPD intervention (n=19) or control (n=11). Participants used SMART-COPD throughout PR and for 8 weeks afterward (ie, maintenance) to set physical activity goals and monitor their progress. Questionnaire-based and physical activity-based outcome measures were taken at baseline, the end of PR, and the end of maintenance. Participants, and health care professionals involved in PR delivery, were interviewed about their experiences with the technology. RESULTS: Overall, 47% (14/30) of participants withdrew from the study. Difficulty in using the technology was a common reason for withdrawal. Participants who completed the study had better baseline health and more prior experience with digital technology, compared with participants who withdrew. Participants who completed the study were generally positive about the technology and found it easy to use. Some participants felt their health had benefitted from using the technology and that it assisted them in achieving physical activity goals. Activity tracking and self-reporting were both found to be problematic as outcome measures of physical activity for this study. There was dissatisfaction among some control group members regarding their allocation. CONCLUSIONS: mHealth shows promise in helping people with COPD self-manage their physical activity levels. mHealth interventions for COPD self-management may be more acceptable to people with prior experience of using digital technology and may be more beneficial if used at an earlier stage of COPD. Simplicity and usability were more important for engagement with the SMART-COPD intervention than personalization; therefore, the intervention should be simplified for future use. Future evaluation will require consideration of individual factors and their effect on mHealth efficacy and use; within-subject comparison of step count values; and an opportunity for control group participants to use the intervention if an RCT were to be carried out. Sample size calculations for a future evaluation would need to consider the high dropout rates.

Use of Autologous Platelets for Lamellar Macular Hole Repair.

The consensus of lamellar macular hole repair generally entails vitrectomy with internal limiting membrane with/without epiretinal membrane peeling with gas tamponade, although the risk of a full thickness macular hole remains. In this case report, we investigate the role of the regenerative properties of autologous platelets in the repair of a lamellar macular hole with pars plana vitrectomy, an autologous platelet plug, and 12% C3F8 without prone posturing. All three patients in this case report experienced visual improvement along with anatomic closure of the lamellar macular hole. Further randomized studies with larger sample sizes will contribute to the existing data regarding this procedure and its outcomes.

A Virtual Agent to Support Individuals Living With Physical and Mental Comorbidities: Co-Design and Acceptability Testing.

BACKGROUND: Individuals living with long-term physical health conditions frequently experience co-occurring mental health problems. This comorbidity has a significant impact on an individual's levels of emotional distress, health outcomes, and associated health care utilization. As health care services struggle to meet demand and care increasingly moves to the community, digital tools are being promoted to support patients to self-manage their health. One such technology is the autonomous virtual agent (chatbot, conversational agent), which uses artificial intelligence (AI) to process the user's written or spoken natural language and then to select or construct the corresponding appropriate responses. OBJECTIVE: This study aimed to co-design the content, functionality, and interface modalities of an autonomous virtual agent to support self-management for patients with an exemplar long-term condition (LTC; chronic pulmonary obstructive disease [COPD]) and then to assess the acceptability and system content. METHODS: We conducted 2 co-design workshops and a proof-of-concept implementation of an autonomous virtual agent with natural language processing capabilities. This implementation formed the basis for video-based scenario testing of acceptability with adults with a diagnosis of COPD and health professionals involved in their care. RESULTS: Adults (n=6) with a diagnosis of COPD and health professionals (n=5) specified 4 priority self-management scenarios for which they would like to receive support: at the time of diagnosis (information provision), during acute exacerbations (crisis support), during periods of low mood (emotional support), and for general self-management (motivation). From the scenario testing, 12 additional adults with COPD felt the system to be both acceptable and engaging, particularly with regard to internet-of-things capabilities. They felt the system would be particularly useful for individuals living alone. CONCLUSIONS: Patients did not explicitly separate mental and physical health needs, although the content they developed for the virtual agent had a clear psychological approach. Supported self-management delivered via an autonomous virtual agent was acceptable to the participants. A co-design process has allowed the research team to identify key design principles, content, and functionality to underpin an autonomous agent for delivering self-management support to older adults living with COPD and potentially other LTCs.

Prolonged systemic inflammation and damage to the vascular endothelium following intratracheal instillation of air pollution nanoparticles in rats.

BACKGROUND: Exposure to air pollution is associated with cardiovascular disease, including increased morbidity and mortality rates. OBJECTIVE: The aim of this investigation was to assess the effect, in rats, of intratracheal instillation of particulate air pollution on biomarkers of leucocyte activation and vascular endothelial damage. METHODS: Air pollution particles (PM10) were instilled into rats, and blood samples were taken three days and six weeks post instillation. Plasma neutrophil elastase and Von Willebrand factor were measured by ELISA. RESULTS: Plasma neutrophil elastase increased from 175±44 ng/ml at baseline to 288±26 ng/ml 3 days post instillation (p = 0.038). vWF increased from 0.160±0.015 IU/ml at baseline to 0.224±0.015 IU/ml at 3 days post and 0.208±0.01 IU/ml at 6 weeks post (p = 0.006, ANOVA). sICAM-1 increased from 17.75±0.70 ng/ml at baseline to 19.03±0.33 ng/ml at 3 days post and 21.72±1.16 ng/ml at 6 weeks post (p = 0.009, ANOVA). CONCLUSION: Instillation caused prolonged systemic inflammation, activation of blood leucocytes and damage to the vascular endothelium.

DEXAMETHASONE INTRAVITREAL IMPLANT FOR X-LINKED (JUVENILE) RETINOSCHISIS.

PURPOSE: Dexamethasone intravitreal corticosteroid implants (OZURDEX) have been used to treat subretinal fluid associated with several retinal diseases. We describe the use of a dexamethasone intravitreal implant for symptomatic management in a case of X-linked (juvenile) retinoschisis (XLRS). METHODS: A 19-year-old man diagnosed with XLRS was treated with a dexamethasone intravitreal implant for his newly symptomatic subretinal fluid. CONCLUSION: Dexamethasone intravitreal implant treatment in the setting of XLRS has not been previously described. To the authors' knowledge, this is the first description of the use of corticosteroid implants to treat symptomatic subretinal fluid in XLRS. Further studies are warranted to investigate the role of corticosteroid implant treatment in XLRS.

Development of Central Serous Chorioretinopathy following Chalazion Removal with Intralesional Triamcinolone Injection: A Case Report.

We report a case of central serous chorioretinopathy (CSC) that developed 1 month after an intralesional injection of triamcinolone acetonide that was administered during removal of a chalazion. The subretinal fluid and ipsilateral visual acuity (VA) worsened with initial observation. The edema resolved with verteporfin photodynamic therapy (PDT) 1 month after diagnosis, but VA did not improve during short-term follow-up. We conclude that CSC can occur as a complication of low-dose intrapalpebral corticosteroid administration and provide another example of the therapeutic role of PDT in the management of this disease.

Computer Interactive Reminiscence and Conversation Aid groups-Delivering cognitive stimulation with technology.

INTRODUCTION: Group-based cognitive stimulation is the only nonpharmacologic intervention recommended by the UK National Institute for Clinical and Health Excellence for people with dementia. The potential of technology to extend the availability of group-based cognitive stimulation has not been tested. METHODS: One hundred sixty-one people with dementia participated in an eight-session group activity using Computer Interactive Reminiscence and Conversation Aid (CIRCA). Cognition, quality of life, and general health were assessed before intervention, postintervention, and 3 months later. RESULTS: There was a significant improvement in cognition and quality of life at the end of the CIRCA group intervention, which was further improved at 3-month follow-up. DISCUSSION: CIRCA group sessions improved cognition and quality of life similar to group-based cognitive stimulation approved by the National Institute for Clinical and Health Excellence. These benefits were maintained at 3-month follow-up. The data confirm the potential of CIRCA, which can be populated with different cultural and language contents for different user groups.

The Hollybank Challenges: AT for People with Profound Disabilities.

The use of Assistive Technology with people with profound and multiple disabilities is a specialised subfield. Drawing on its authors' experiences and observations at a UK charitable foundation that offers specialised educational, residential and therapeutic facilities, this paper describes the distinct challenges that present themselves when applying AT to address the needs of this often-overlooked sector of the community. It is hoped that this will help raise awareness and contribute to improving the overall quality of AT provision in this area.

The effect of physical activity on haematological predictors of cardiovascular risk: evidence of a dose response.

Cardiovascular disease is a major cause of morbidity and mortality in the developed world. Large epidemiological studies have reported a strong association between increases in haematological factors and increased cardiovascular risk. Haematological risk factors predicted cardiovascular disease at least as strongly as traditional risk factors such as blood lipid concentrations. Lifestyle factors such as physical activity level could significantly reduce risk. The aim of this study was to determine the effect of physical activity level on haematological predictors of cardiovascular risk. Healthy subjects (156) were recruited. Physical activity in subjects was assessed by IPAQ physical activity questionnaire. Blood was collected and blood cell counts were determined by automated cell counter; neutrophil elastase was determined by ELISA. Increased levels of physical activity were associated with reduced red cell (p = 0.001), white cell (p = 0.002) and platelet counts (p = 0.001) and with reduced plasma neutrophil elastase concentration (p = 0.001). There was a continuous linear relationship between increase in physical activity and decrease in haematological risk factors. Hence, the authors conclude that increased levels of physical activity improve the flow properties of blood and thus reduce the risk of developing cardiovascular disease. Even small increases in activity result in some reduction in cardiovascular risk.

Exercise-induced immunosuppression: roles of reactive oxygen species and 5'-AMP-activated protein kinase dephosphorylation within immune cells.

We previously proposed 5'-AMP-activated protein kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. In this study, AMPK phosphorylation underwent transient (<1 h) decreases (53.8+/-7.2% basal) immediately after exercise (45 min of cycling at 70% VO2max) in a cohort of 16 adult male participants. Similar effects were seen with running. However, because exercise-induced inactivation of AMPK was previously shown to occur in an AMP-independent manner, the means by which AMPK is inactivated in this context is not yet clear. To investigate the hypothesis that exercise-induced inactivation of AMPK is mediated via signaling mechanisms distinct from changes in cellular AMP-to-ATP ratios, reactive oxygen species (ROS) and intracellular Ca2+ signaling were investigated in mononuclear cells before and after exercise and in cultured monocytic MM6 cells. In in vitro studies, treatment with an antioxidant (ascorbic acid, 4 h, 50 microM) decreased MM6 cell intracellular ROS levels (88.0+/-5.2% basal) and induced dephosphorylation of AMPK (44.7+/-17.6% basal). By analogy, the fact that exercise decreased mononuclear cell ROS content (32.8+/-16.6% basal), possibly due to downregulation (43.4+/-8.0% basal) of mRNA for NOX2, the catalytic subunit of the cytoplasmic ROS-generating enzyme NADPH oxidase, may provide an explanation for the AMPK-dephosphorylating effect of exercise. In contrast, exercise-induced Ca2+ signaling events did not seem to be coupled to changes in AMPK activity. Thus we propose that the exercise-induced decreases in both intracellular ROS and AMPK phosphorylation seen in this study constitute evidence supporting a role for ROS in controlling AMPK, and hence immune function, in the context of exercise-induced immunosuppression.