The Application of Integrated Knowledge-based Systems for the Biomedical Risk Assessment Intelligent Network (BRAIN)

One of NASA's goals for long duration space flight is to maintain acceptable levels of crew health, safety, and performance. One way of meeting this goal is through the Biomedical Risk Assessment Intelligent Network (BRAIN), an integrated network of both human and computer elements. The BRAIN will function as an advisor to flight surgeons by assessing the risk of in-flight biomedical problems and recommending appropriate countermeasures. This paper describes the joint effort among various NASA elements to develop BRAIN and an Infectious Disease Risk Assessment (IDRA) prototype. The implementation of this effort addresses the technological aspects of the following: (1) knowledge acquisition; (2) integration of IDRA components; (3) use of expert systems to automate the biomedical prediction process; (4) development of a user-friendly interface; and (5) integration of the IDRA prototype and Exercise Countermeasures Intelligent System (ExerCISys). Because the C Language, CLIPS (the C Language Integrated Production System), and the X-Window System were portable and easily integrated, they were chosen as the tools for the initial IDRA prototype. The feasibility was tested by developing an IDRA prototype that predicts the individual risk of influenza. The application of knowledge-based systems to risk assessment is of great market value to the medical technology industry

Enhancing Employees’ Health and Well-being: Developing a Successful Holistic Wellness Challenge

Improving the overall health and wellness of employees is an important focus of many organizations. Healthy employees experience more job satisfaction and productivity. The University of Calgary offers programs and services that promote healthy living, a healthy work environment, and respect the employees’ lives outside of work as well as their work life. Collaborating with the university’s WellBeing and Work Life department, the purpose of our community health promotion project was to develop and provide recommendations for the implementation of a successful holistic wellness challenge for faculty and staff. Drawing on the Population Health Promotion Model, the Community as Partner model, and the nursing process, a windshield survey, key informant interviews, a focused review of literature, and an environmental scan of 15 Canadian universities (U15) and Vanderbilt University (well-known for its excellent occupational health program).  The information gained was used to create then pilot a holistic evidence-based challenge that aims to improve employees’ physical activity, exercise, mental health, social health, financial health, and nutrition. To increase community members’ awareness and participation in the wellness challenge, we developed brochures detail the health benefits to be gained and offer suggestions for implementing each component. Because our evidence-based recommendations are feasible and flexible with clear marketing strategies, they are more likely to be adopted by organizations and their employees

Emission-Line Galaxies from the Hubble Space Telescope Probing Evolution and Reionization Spectroscopically (PEARS) Grism Survey. II: The Complete Sample

We present a full analysis of the Probing Evolution And Reionization Spectroscopically (PEARS) slitess grism spectroscopic data obtained with the Advanced Camera for Surveys on HST. PEARS covers fields within both the Great Observatories Origins Deep Survey (GOODS) North and South fields, making it ideal as a random survey of galaxies, as well as the availability of a wide variety of ancillary observations to support the spectroscopic results. Using the PEARS data we are able to identify star forming galaxies within the redshift volume 0< z<1.5. Star forming regions in the PEARS survey are pinpointed independently of the host galaxy. This method allows us to detect the presence of multiple emission line regions (ELRs) within a single galaxy. 1162 Ha, [OIII] and/or [OII] emission lines have been identified in the PEARS sample of ~906 galaxies down to a limiting flux of ~1e-18 erg/s/cm^2. The ELRs have also been compared to the properties of the host galaxy, including morphology, luminosity, and mass. From this analysis we find three key results: 1) The computed line luminosities show evidence of a flattening in the luminosity function with increasing redshift; 2) The star forming systems show evidence of disturbed morphologies, with star formation occurring predominantly within one effective (half-light) radius. However, the morphologies show no correlation with host stellar mass; and 3) The number density of star forming galaxies with M_* > 1e9} M_sun decreases by an order of magnitude at z<0.5 relative to the number at 0.5<z<0.9 in support of the argument for galaxy downsizing.Comment: Submitted. 48 pages. 19 figures. Accepted to Ap

Is pre-operative urodynamic bladder function the true predictor of outcome of male sling for post prostatectomy incontinence?

PURPOSE: To investigate pre-operative urodynamic parameters in male sling patients to ascertain whether this might better predict surgical outcomes and facilitate patient selection. METHODS: We performed a retrospective, case notes and video-urodynamics, review of men who underwent AdVanceXP male sling in three London hospitals between 2012 and 2019. Urodynamics were performed in all centres, while retrograde leak point pressure (RLPP) was performed in one centre. RESULTS: Successful outcome was seen in 99/130 (76%) of men who required one pad or less per day. The dry rate was 51%. Pad usage was linked to worse surgical outcomes, mean 2.6 (range 1-6.5) for success vs 3.6 (range 1-10) although the ranges were wide (p = 0.002). 24 h pad weight also reached statistical significance (p = 0.05), with a mean of 181 g for success group versus 475 g for the non-successful group. The incidence of DO in the non-successful group was significantly higher than in successful group (55% versus 29%, p = 0.0009). Bladder capacity less than 250 ml was also associated with worse outcomes (p = 0.003). Reduced compliance was not correlated with outcomes (31% for success groups vs 45% for non-successful group, p = 0.15). Preoperative RLPP was performed in 60/130 patients but did not independently reach statistical significance (p = 0.25). CONCLUSION: Urodynamic parameters related to bladder function-detrusor overactivity and reduced maximum cystometric capacity predict male sling outcomes and may help in patient selection for male sling (or sphincter) surgery; whereas urodynamic parameters of sphincter incompetency (RLPP) were not predictive. Further larger scale studies are required to confirm these findings

The Geriatric Emergency Care Applied Research (GEAR) network approach: A protocol to advance stakeholder consensus and research priorities in geriatrics and dementia care in the emergency department

INTRODUCTION: Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs-to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia. METHODS AND ANALYSIS: In this paper, we describe our approach to developing the GEAR Network infrastructure, the scoping reviews to identify research and clinical gaps and its use of consensus-driven research priorities with a transdisciplinary taskforce of stakeholders that includes patients and care partners. We describe how priority topic areas are ascertained, the process of conducting scoping reviews with integrated academic librarians performing standardised searches and providing quality control on reviews, input and support from the taskforce and conducting a large-scale consensus workshop to prioritise future research topics. The GEAR Network approach provides a framework and systematic approach to develop a research agenda and support research in geriatric emergency care. ETHICS AND DISSEMINATION: This is a systematic review of previously conducted research; accordingly, it does not constitute human subjects research needing ethics review. These reviews will be prepared as manuscripts and submitted for publication to peer-reviewed journals, and the results will be presented at conferences.Open Science Framework registered DOI: 10.17605/OSF.IO/6QRYX, 10.17605/OSF.IO/AKVZ8, 10.17605/OSF.IO/EPVR5, 10.17605/OSF.IO/VXPRS

Learning from Participatory Research and Action Approaches to Transforming Food Systems

Now more than ever, evidence overwhelmingly concludes that our food systems are not currently working to nourish our populations, ecosystems, economies, or social connectionNow more than ever, evidence overwhelmingly concludes that our food systems are not currently working to nourish our populations, ecosystems, economies, or social connections. Agroecological approaches have been shown as having potential to address many of these problems in the mainstream food system, particularly when combined with concepts of food sovereignty, which localise control, and place producers and consumers at the centre of decision-making (Pretty et al 2006, Chappell and LaValle 2009, Sevilla Guzman and Woodgate 2003). However, knowing the principles and the end goals, while invaluable, is not enough. We need to transition from the food systems we currently have to the food systems we envision for future generations. Where do we begin and who should lead that process? In line with principles of food sovereignty, that transition needs to be led and owned not by outside experts or researchers but by the people most directly affected by and typically excluded from decision making within the current food system (i.e. small- and medium -scale farmers, workers involved in harvesting and food processing, cottage manufacturers and consumers across socioeconomic classes). It must also respond to the current level of globalisation of our food systems. For example, a decision to localise consumption in one country can greatly affect export-focused producers and economies in another

Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification

© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo

Development of a Novel, Ultra-rapid Biosensor for the Qualitative Detection of Hepatitis B Virus-associated Antigens and Anti-HBV, Based on “Membrane-engineered” Fibroblast Cells with Virus-Specific Antibodies and Antigens

A novel miniature cell biosensor detection system for the detection of Hepatis B virus (HBV)-associated antigens and anti-HBV is described. The biosensor is based on “membrane-engineered” Vero fibroblast cells immobilized in an alginate matrix. The membrane-engineering process involved the electroinsertion of anti-HBV specific antibodies (anti-HBs, anti-HBe) or antigens (HBsAg) in the membranes of the Vero cells. The attachment of a homologous antigen to the electroinserted antibody (or, respectively, of the antibody to the electroinserted antigen) triggered specific changes to the cell membrane potential that were measured by appropriate microelectrodes, according to the principle of the Bioelectric Recognition Assay (BERA). The sensor was used for screening 133 clinical blood serum samples according to a double-blind protocol. Considerably higher sensor responses were observed against HBV-positive samples, compared with responses against negative samples or samples positive for heterologous hepatitis viruses such as Hepatitis C (HCV) virus. Detection of anti-HBs antibodies was made possible by using a biosensor based on immobilized Vero cells bearing the respective antigen (HBsAg). The observed response was rapid (45 sec) and quite reproducible. Fluorescence microscopy observations showed that attachment of HBV particles to cells membrane-engineered with anti-HBs was associated with a decrease of [Ca2+]cyt. The perspectives for using the novel biosensor as a qualitative, rapid screening, high throughput assay for HBV antigens and anti-HBs in clinical samples is discussed

Biases in probabilistic category learning in relation to social anxiety.

Instrumental learning paradigms are rarely employed to investigate the mechanisms underlying acquired fear responses in social anxiety. Here, we adapted a probabilistic category learning paradigm to assess information processing biases as a function of the degree of social anxiety traits in a sample of healthy individuals without a diagnosis of social phobia. Participants were presented with three pairs of neutral faces with differing probabilistic accuracy contingencies (A/B: 80/20, C/D: 70/30, E/F: 60/40). Upon making their choice, negative and positive feedback was conveyed using angry and happy faces, respectively. The highly socially anxious group showed a strong tendency to be more accurate at learning the probability contingency associated with the most ambiguous stimulus pair (E/F: 60/40). Moreover, when pairing the most positively reinforced stimulus or the most negatively reinforced stimulus with all the other stimuli in a test phase, the highly socially anxious group avoided the most negatively reinforced stimulus significantly more than the control group. The results are discussed with reference to avoidance learning and hypersensitivity to negative socially evaluative information associated with social anxiety

Deep Proteome Analysis Identifies Age-Related Processes in <i>C. elegans</i>

SummaryEffective network analysis of protein data requires high-quality proteomic datasets. Here, we report a near doubling in coverage of the C. elegans adult proteome, identifying >11,000 proteins in total with ∼9,400 proteins reproducibly detected in three biological replicates. Using quantitative mass spectrometry, we identify proteins whose abundances vary with age, revealing a concerted downregulation of proteins involved in specific metabolic pathways and upregulation of cellular stress responses with advancing age. Among these are ∼30 peroxisomal proteins, including the PRX-5/PEX5 import protein. Functional experiments confirm that protein import into the peroxisome is compromised in vivo in old animals. We also studied the behavior of the set of age-variant proteins in chronologically age-matched, long-lived daf-2 insulin/IGF-1-pathway mutants. Unexpectedly, the levels of many of these age-variant proteins did not scale with extended lifespan. This indicates that, despite their youthful appearance and extended lifespans, not all aspects of aging are reset in these long-lived mutants