Interactions in Sociotechnical Systems: Achieving Balance in the Use of an Augmented Reality Mobile Application.

OBJECTIVE: We explore relationships between barriers and facilitators experienced by users to understand dynamic interactions in sociotechnical systems and improve a mobile phone-based augmented reality application that teaches users about the contents of a standardized pediatric code cart. BACKGROUND: Understanding interactions between performance obstacles and facilitators can provide guidance to (re)designing sociotechnical systems to improve system outcomes. Clinicians should know about contents and organization of code carts, and an augmented reality mobile application may improve that knowledge but changes the sociotechnical system in which they learn. Prior work identified barriers and facilitators impacting the use of this application-participants described dimensions together, indicating interactions that are explored in the current study. METHOD: We conducted four focus groups (number of clinicians = 18) and two interviews with clinicians who used the application. We performed a secondary analysis of focus group data exploring interactions between previously identified barriers and facilitators to application use. We used epistemic network analysis to visualize these interactions. RESULTS: Work system barriers interacted with barriers and facilitators interacted with facilitators to amplify cumulative negative or positive impact, respectively. Facilitators balanced barriers, mitigating negative impact. Facilitators also exacerbated barriers, worsening negative impact. CONCLUSION: Barriers and facilitators interact and can amplify, balance, and exacerbate each other-notably, positives are not always positive. To obtain desired outcomes, interactions must be further considered in sociotechnical system design, for example, the potential improvements to the application we identified.

Walking the line: balancing performance barriers and facilitators in an augmented reality mobile application for paediatric code cart training.

An augmented reality (AR) mobile smartphone application was developed for clinicians to improve their knowledge about the contents and organisation of a standardised paediatric code cart, an important tool in safe, effective paediatric resuscitations. This study used focus groups and interviews with 22 clinicians to identify work system barriers and facilitators to use of the application. We identified twelve dimensions of barriers and facilitators: convenience, device ownership, device size and type, gamification, interface design, movement/physical space, perception of others, spatial presence, technological experience, technological glitches, workload, and the perception and attitude towards code cart and resuscitation. These dimensions can guide improvement efforts, e.g. redesigning the interface, providing non-AR modes, improving the tutorial. We propose nine principles to guide the design of other digital health technologies incorporating AR. In particular, the workload demands created by using AR must be considered and accounted for in the design and implementation of such technologies. Practitioner summary: Augmented reality (AR) may prepare workers for situations that do not occur frequently. This study investigates barriers and facilitators to using an AR mobile smartphone application developed to improve clinician knowledge about code carts, leading to improvements to the application and principles to guide the design of other AR-based technologies.

Stable Particle Acceleration in Coaxial Plasma Channels.

The attainable transformer ratio in plasma accelerators is limited by instabilities. Using three-dimensional particle-in-cell simulations, we demonstrate that these can be controlled using a hollow plasma channel with a coaxial plasma filament. The driver scatters electrons from the filament, and the slow pinch of the ions leads to a strong chirp of the effective betatron frequency, preventing beam breakup. We demonstrate the monoenergetic acceleration of an electron bunch to 20 GeV over 4.4 m, achieving a transformer ratio of 10, an energy efficiency of 40%, and an emittance of 1.8 µm.

Arabidopsis AtSUC2 and AtSUC4, encoding sucrose transporters, are required for abiotic stress tolerance in an ABA-dependent pathway.

Sucrose transporters (SUCs or SUTs) play a central role, as they orchestrate sucrose allocation both intracellularly and at the whole plant level. Previously, we found AtSUC4 mutants changing sucrose distribution under drought and salt stresses. Here, we systematically examined the role of Arabidopsis AtSUC2 and AtSUC4 in response to abiotic stress. The results showed significant induction of AtSUC2 and AtSUC4 in salt, osmotic, low temperature and exogenous abscisic acid (ABA) treatments by public microarray data and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses. The loss-of-function mutation of AtSUC2 and AtSUC4 led to hypersensitive responses to abiotic stress and ABA treatment in seed germination and seedling growth. These mutants also showed higher sucrose content in shoots and lower sucrose content in roots, as compared with that in wild-type plants, and inhibited the ABA-induced expression of many stress- and ABA-responsive genes, especially ABFs and ABF-downstream and upstream genes. The loss-of-function mutant of AtSUC3, a unique putative sucrose sensor, reduced the expression of AtSUC2 and AtSUC4 in response to abiotic stresses and ABA. These findings confirmed that AtSUC2 and AtSUC4 are important regulators in plant abiotic stress tolerance that use an ABA signaling pathway, which may be crossed with sucrose signaling.

Arterial stiffness as a risk factor for coronary artery disease.

Hypertension is a major modifiable risk factor, and clinical trials have demonstrated that successful reduction of elevated blood pressure to target levels translates into decreased risk for the development of coronary artery disease, stroke, heart failure, and renal failure. The arterial system had previously been regarded as a passive conduit for the transportation of arterial blood to peripheral tissues. The physiologic role the arterial system was greatly expanded by the recognition of the central role of the endothelial function in a variety of physiologic processes. The role of arterial function and structure in cardiovascular physiology was expanded with the development of a variety of parameters that evaluate arterial stiffness. Markers of arterial stiffness have been correlated with cardiovascular outcomes, and have been classified as an emerging risk factor that provides prognostic information beyond standard stratification strategies involving hypertension, diabetes, obesity, dyslipidemia and smoking. Multiple epidemiologic studies have correlated markers of arterial stiffness such as pulse-wave velocity, augmentation index and pulse pressure with risk for the development of fatal and nonfatal cardiovascular events. Additionally, measurements of arterial stiffness had clarified the results of clinical trials that demonstrated differing impacts on clinical outcomes, despite similar reductions in blood pressure, as measured by brachial and sphygmomanometry.

Aggressive statin therapy and the risk of malignancy.

The advent of pharmacologic agents which partially inhibit the rate limiting enzyme in cholesterol synthesis (3-hydroxy-3-methylglutaryl Co-A reductase) provided a major advance in preventive medicine. Clinical trials in both primary and secondary prevention have demonstrated reduction in cardiovascular events by statin therapy. However, early epidemiologic studies proposed an inverse relationship between cholesterol levels and mortality. While the epidemiologic studies were controversial and did not establish a cause and effect relationship, concern was raised that aggressive lipid lowering by pharmacological means may be associated with increased risk for noncardiac mortality, including malignancy. The theoretical concern was intensified by meta-analysis of statin trials, which confirmed the reduction in cardiovascular mortality but also demonstrated a potential increase in cancer risk. This review evaluates the epidemiologic and prospective trial data which address the potential relationship between aggressive statin therapy and the risk of malignancy.

High-density lipoprotein and atherosclerosis: the role of antioxidant activity.

Levels of high-density lipoprotein (HDL) cholesterol are generally inversely associated with the risk for the development of atherosclerosis. The mechanism by which HDL imparts protection from the initiation and progression of occlusive vascular disease is complex and multifactorial. The major anti-atherosclerotic effect of HDL is felt to be reverse cholesterol transport. HDL has been demonstrated to scavenge cholesterol from the peripheral vasculature with transport to the liver, where is it excreted in the biliary system. However, HDL exhibits multiple other physiologic effects that may play a role in the reduced risk for atherosclerosis. HDL has been demonstrated to exhibit beneficial effects on platelet function, endothelial function, coagulation parameters, inflammation, and interactions with triglyceride-rich lipoproteins. Increasing amounts of clinical and experimental data have shown that HDL cholesterol has significant antioxidant effect that may significantly contribute to protection from atherosclerosis.

Evolving concepts of the role of high-density lipoprotein in protection from atherosclerosis.

High-density lipoprotein (HDL) is classified as a negative risk factor due to the inverse relationship between elevated levels of HDL cholesterol and atherosclerosis. The mechanism by which HDL can mediate protection from atherosclerosis is complex and multifactorial. The primary role of reverse cholesterol transport in the reduction of risk for coronary artery disease is supported by a considerable amount of experimental data. HDL is able to interact with and remove cholesterol from the lipid-laden foam cells in the peripheral vasculature with subsequent transportation to the liver for excretion. However, HDL has multiple other physiologic effects that may play a significant role in protection from atherosclerosis. HDL has been demonstrated to exhibit multiple beneficial effects on the coagulation system. Platelet function is improved by both direct and indirect mechanisms. HDL has a complex interaction with the protein C and protein S system. Thrombolytic balance is also improved by HDL. HDL has been demonstrated to have a significant natural antioxidant effect that inhibits the oxidative step required for low-density lipoprotein uptake by the macrophage. Additionally, HDL has also been demonstrated to exert multiple beneficial effects on endothelial function, including decreased apoptosis and endothelial repair.

Scottish peat bog records of atmospheric vanadium deposition over the past 150 years: comparison with other records and emission trends.

Cores from four Scottish ombrotrophic peat bogs were used to reconstruct the historical record of atmospheric vanadium (V) deposition in Scotland over the last 150 years. The general similarity of V and Pb concentration profile trends in (210)Pb-dated cores from each of the sites strongly suggested that V, like Pb, is essentially immobile in ombrotrophic peat. After allowance via use of the conservative element Ti for the contribution of soil dust V, the deposition of anthropogenic V was found to be greatest (∼ 1.3 to 2.0 mg m(-2) y(-1)) in the mid-20(th) century before decreasing to 0.1-0.3 mg m(-2) y(-1) in the early years of the 21(st) century. The latter values were in good agreement with directly measured atmospheric V fluxes at nearby sites, a finding also observed in the case of Pb. The decline in peat-core-derived fluxes for both V and Pb from 1970 to 2004, however, was not as large as the decline in official UK emission estimates for the two metals during this period. This, along with an order of magnitude discrepancy between the anthropogenic V/Pb ratios at the peat core surface and the higher values of the ratio for UK emissions in the early 2000s, suggests that the recently revised UK emissions data for V may perhaps still be overestimated and/or that some previously deposited Pb is being resuspended in the atmosphere.

SARS-CoV-2 Spike Pseudoviruses: A Useful Tool to Study Virus Entry and Address Emerging Neutralization Escape Phenotypes.

SARS-CoV-2 genetic variants are emerging around the globe. Unfortunately, several SARS-CoV-2 variants, especially variants of concern (VOCs), are less susceptible to neutralization by the convalescent and post-vaccination sera, raising concerns of increased disease transmissibility and severity. Recent data suggests that SARS-CoV-2 neutralizing antibody levels are a reliable correlate of vaccine-mediated protection. However, currently used BSL3-based virus micro-neutralization (MN) assays are more laborious, time-consuming, and expensive, underscoring the need for BSL2-based, cost-effective neutralization assays against SARS-CoV-2 variants. In light of this unmet need, we have developed a BSL-2 pseudovirus-based neutralization assay (PBNA) in cells expressing the human angiotensin-converting enzyme-2 (hACE2) receptor for SARS-CoV-2. The assay is reproducible (R2 = 0.96), demonstrates a good dynamic range and high sensitivity. Our data suggest that the biological Anti-SARS-CoV-2 research reagents such as NIBSC 20/130 show lower neutralization against B.1.351 SA (South Africa) and B.1.1.7 UK (United Kingdom) VOC, whereas a commercially available monoclonal antibody MM43 retains activity against both these variants. SARS-CoV-2 spike PBNAs for VOCs would be useful tools to measure the neutralization ability of candidate vaccines in both preclinical models and clinical trials and would further help develop effective prophylactic countermeasures against emerging neutralization escape phenotypes.

Statins as adjunctive therapy in the management of hypertension.

The effective optimization of the modifiable risk factors for the development of atherosclerosis is the cornerstone preventive cardiology. Risk factor clustering has been demonstrated to occur in a higher prevalence than would be expected by chance alone. The common cardiovascular risk factors frequently share metabolic pathways. Inflammation and oxidative stress are demonstrable in the major cardiovascular risk factors. Hypertension and dyslipidemia frequently co-exist in an individual. The advent of statin therapy has allowed optimization of the lipid profile and achievement of therapeutic goals advocated by the Adult Treatment Panel of the National Cholesterol Education Program. Statin therapy has been demonstrated to exhibit a wide variety of nonlipid or pleiotropic effects. Observational studies have demonstrated that statin therapy may cause a small but statistically significant alteration of blood pressure. Prospective clinical trials have demonstrated that statin therapy reduces this cardiovascular risk in both hypertensive and normotensive individuals. The potential role of statin therapy in blood pressure reduction is compatible with several pleiotropic mechanisms of statin therapy. However, a significant body of data from prospective, well-designed, controlled clinical trials that have analyzed the effect of statin therapy on blood pressure as the primary end point is lacking. This review examines the observational relationship between hypertension and dyslipidemia, the potential mechanisms by which statin therapy may lower blood pressure, and selected clinical trial data.

Dysfunctional high-density lipoprotein and atherosclerosis.

High-density lipoprotein (HDL) is well established as a negative risk factor for the development of atherosclerosis. Epidemiologic, pathologic, and experimental studies have demonstrated a role for HDL in protection from coronary artery disease. HDL has been demonstrated to reduce the risk from atherosclerosis by multiple pathophysiologic mechanisms. Low-density lipoprotein is a metabolic end product that can be recognized and cleared by specific hepatic receptors with excretion into the bile. However, low-density lipoprotein may also be scavenged in the periphery by the monocyte-macrophage system, with subsequent generation of lipid-laden foam cells. HDL may reduce the atherosclerotic burden by multiple potential mechanisms. HDL can interact with the foam cell to remove cholesterol via receptor-mediated binding, passive diffusion, and alteration of intracellular cholesterol trafficking by ATP binding cassettes. The process of reverse cholesterol transport is a major mechanism by which HDL can remove cholesterol from the periphery, allowing it to be cleared by the liver and then excreted into the bile. However, HDL exhibits multiple additional potential beneficial physiologic effects. Endothelial function and repair is potentiated by HDL. Normal HDL has significant anti-inflammatory and antioxidant activity. Prostacyclin production and improvement in fibrinolytic balance is also attributed to normally functioning HDL. HDL is also intimately related to the metabolism of other circulating lipoproteins. However, multiple clinical studies have identified individuals with a significant atherosclerotic burden despite normal or elevated levels of HDL cholesterol. Clinical conditions associated with inflammation and oxidative stress have adversely altered the normal functions of HDL. Clinical assays have been developed to assess the functionality of HDL. Dysfunctional HDL may be returned to normal by diet, exercise, degree of fat intake, and pharmacologic approaches. Orally active mimetic proteins are in development and have shown clinical promise.

Nicotinic acid: a new look at an old drug.

Dyslipidemia is central to the process of atherosclerosis. Modification of the lipid profile by diet, exercise, or pharmacologic therapy has been demonstrated to reduce the risk from atherosclerosis in clinical studies in primary and secondary prevention. Nicotinic acid has been in clinical use for over 50 years. The administration of nicotinic acid has been demonstrated to reduce apolipoprotein B-containing lipoproteins (very low-density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and lipoprotein (a)). Nicotinic acid also exerts significant effects on high-density lipoprotein. In addition to improving dyslipidemia, nicotinic acid has been demonstrated to induce a number of nonlipid or pleiotropic effects. The recent discovery of the nicotinic acid receptor has improved knowledge relative to the mechanism of action and the adverse effect profile of nicotinic acid. Clinical trials utilizing clinical or angiographic end points demonstrated efficacy for the use of nicotinic acid in monotherapy or in combination with bile acid resins or statins.

The role of statin therapy in the management of cardiomyopathies.

The non-lipid-lowering or pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been hypothesized to beneficially alter mechanisms involved in heart failure. Retrospective analyses of heart failure trials as well as small prospective trials with nonmortality clinical and surrogate end points appeared to confirm this presumption. However, two recently published, large, prospective randomized trials did not demonstrate any significant clinical benefit of statins in heart failure patients. This review outlines the proposed biologic effects of statins in heart failure syndrome and clinical evidence of statin use in heart failure patients.

Strategies for improving human health in contaminated situations: a review of past, present and possible future approaches.

Strategies for improving human health in contaminated situations have traditionally been based on restricting emissions, remedial reduction of exposure and, where appropriate and possible, medical reconnaissance of efficacy. We review these and the broader aspects of general public health approaches, including necessary understanding of epidemiology and the wider social context, before considering a specific local case study involving health issues associated with chromium-contaminated land and its remediation in an area of urban regeneration. The impact of remediation upon the common good, in its broadest environmental, health and socio-economic sense, including enhanced opportunities for members of the community to take personal responsibility for health-improving activities, should be taken into account in addition to conventional theoretical assessments and practical measurements of relief from environmental risk. Rapidly emerging toxicogenomic technologies may have a role to play in informing future risk assessment and remediation approaches in contaminated situations, although the ethical challenges of using personal genetic information could well be considerable.

Adjunctive interventions in myocardial infarction: the role of statin therapy.

Statin therapy has reduced cardiovascular morbidity and mortality across the spectrum of atherosclerosis. The administration of statins has been demonstrated to be effective in primary and secondary prevention clinical trials evaluating patients with high and low risk-factor profiles. The presumed mechanism of benefit of hypolipidemic therapy in the prevention of atherosclerotic disease was a reduction in the deposition of atherogenic lipoproteins in vulnerable areas of the coronary vasculature. Subsequent experimental studies with statins demonstrated a variety of potentially beneficial effects that would extend clinical benefit beyond lipid-lowering per se. Statin therapy beneficially alters inflammation, coagulation and fibrinolytic parameters, endothelial function, vasoreactivity, and platelet function. The demonstration of the non-lipid or pleiotropic effects provided the theoretical basis for a possible role as an adjunctive therapy in acute coronary syndromes. Retrospective analysis of a variety of early trials indicated a potential benefit of statins during acute ischemic syndromes. Recent clinical trials have addressed this important clinical question in a prospective controlled manner. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) and the Thrombolysis In Myocardial Infarction (TIMI)-22 studies present strong clinical evidence in favor of the administration of statins as adjunctive therapy in acute ischemic syndromes.

Diabetic dyslipidemia and atherosclerosis: evidence from clinical trials.

Diabetes is a highly prevalent disease in the United States and is increasing in both incidence and prevalence. Atherosclerotic vascular disease is a major cause of morbidity and mortality in diabetic patients. Type 2 diabetes is characterized by insulin resistance and frequently co-exists with a variety of cardiovascular risk factors, including hypertension, obesity, dyslipidemia, and physical inactivity. Hygienic measures such as weight loss and exercise should form the basis of therapeutic interventions in the prevention and treatment of type 2 diabetes. The role of dyslipidemia as a causal factor in vascular disease associated with diabetes was previously downplayed because total cholesterol was frequently normal or minimally elevated. However, diabetic dyslipidemia is characterized by elevated triglycerides, low high-density lipoprotein, and small, dense low-density lipoprotein, the combination of which has been termed the "lipid triad." The role of lipid modification as a means to decrease cardiovascular risk in type 2 diabetes has recently been clarified by a number of clinical trials. Subgroup analysis in early studies implied the potential for benefit of lipid modification in diabetes. The results of these early studies prompted the design of large-scale intervention trials that employed statin and fibric acid derivatives in diabetes patients. The preponderance of data from the statin trials implicates significant clinical benefit in cardiovascular risk reduction. The fibric acid derivatives have theoretic advantages in diabetic dyslipidemia. However, the robust bulk of clinical data obtained from prospective statin studies is lacking for the fibric acid derivatives, and the results of the major trials are equivocal.

An integrated colloid fractionation approach applied to the characterisation of porewater uranium-humic interactions at a depleted uranium contaminated site.

Methods for the fractionation of aquatic colloids require careful application to ensure efficient, accurate and reproducible separations. This paper describes the novel combination of mild colloidal fractionation and characterisation methods, namely centrifugal ultrafiltration, gel electrophoresis and gel filtration along with spectroscopic (UV-visible) and elemental (Inductively Coupled Plasma-Optical Emission Spectroscopy, Inductively Coupled Plasma-Mass Spectrometry) analysis, an approach which produced highly consistent results, providing improved confidence in these methods. Application to the study of the colloidal and dissolved components of soil porewaters from one soil at a depleted uranium (DU)-contaminated site revealed uranium (U) associations with both large (100 kDa-0.2 microm) and small (3-30 kDa) humic colloids. For a nearby soil with lower organic matter content, however, association with large (100 kDa-0.2 microm) iron (Fe)-aluminium (Al) colloids in addition to an association with small (3-30 kDa) humic colloids was observed. The integrated colloid fractionation approach presented herein can now be applied with confidence to investigate U and indeed other trace metal migration in soil and aquatic systems.