Shaping bursting by electrical coupling and noise

Gap-junctional coupling is an important way of communication between neurons and other excitable cells. Strong electrical coupling synchronizes activity across cell ensembles. Surprisingly, in the presence of noise synchronous oscillations generated by an electrically coupled network may differ qualitatively from the oscillations produced by uncoupled individual cells forming the network. A prominent example of such behavior is the synchronized bursting in islets of Langerhans formed by pancreatic \beta-cells, which in isolation are known to exhibit irregular spiking. At the heart of this intriguing phenomenon lies denoising, a remarkable ability of electrical coupling to diminish the effects of noise acting on individual cells. In this paper, we derive quantitative estimates characterizing denoising in electrically coupled networks of conductance-based models of square wave bursting cells. Our analysis reveals the interplay of the intrinsic properties of the individual cells and network topology and their respective contributions to this important effect. In particular, we show that networks on graphs with large algebraic connectivity or small total effective resistance are better equipped for implementing denoising. As a by-product of the analysis of denoising, we analytically estimate the rate with which trajectories converge to the synchronization subspace and the stability of the latter to random perturbations. These estimates reveal the role of the network topology in synchronization. The analysis is complemented by numerical simulations of electrically coupled conductance-based networks. Taken together, these results explain the mechanisms underlying synchronization and denoising in an important class of biological models

Aiding first incident responders using a decision support system based on live drone feeds

In case of a dangerous incident, such as a fire, a collision or an earthquake, a lot of contextual data is available for the first incident responders when handling this incident. Based on this data, a commander on scene or dispatchers need to make split-second decisions to get a good overview on the situation and to avoid further injuries or risks. Therefore, we propose a decision support system that can aid incident responders on scene in prioritizing the rescue efforts that need to be addressed. The system collects relevant data from a custom designed drone by detecting objects such as firefighters, fires, victims, fuel tanks, etc. The drone autonomously observes the incident area, and based on the detected information it proposes a prioritized based action list on e.g. urgency or danger to incident responders

A dynamic network approach for the study of human phenotypes

The use of networks to integrate different genetic, proteomic, and metabolic datasets has been proposed as a viable path toward elucidating the origins of specific diseases. Here we introduce a new phenotypic database summarizing correlations obtained from the disease history of more than 30 million patients in a Phenotypic Disease Network (PDN). We present evidence that the structure of the PDN is relevant to the understanding of illness progression by showing that (1) patients develop diseases close in the network to those they already have; (2) the progression of disease along the links of the network is different for patients of different genders and ethnicities; (3) patients diagnosed with diseases which are more highly connected in the PDN tend to die sooner than those affected by less connected diseases; and (4) diseases that tend to be preceded by others in the PDN tend to be more connected than diseases that precede other illnesses, and are associated with higher degrees of mortality. Our findings show that disease progression can be represented and studied using network methods, offering the potential to enhance our understanding of the origin and evolution of human diseases. The dataset introduced here, released concurrently with this publication, represents the largest relational phenotypic resource publicly available to the research community.Comment: 28 pages (double space), 6 figure

Neighbourhood, Route and Workplace-Related Environmental Characteristics Predict Adults' Mode of Travel to Work

Commuting provides opportunities for regular physical activity which can reduce the risk of chronic disease. Commuters' mode of travel may be shaped by their environment, but understanding of which specific environmental characteristics are most important and might form targets for intervention is limited. This study investigated associations between mode choice and a range of objectively assessed environmental characteristics.Participants in the Commuting and Health in Cambridge study reported where they lived and worked, their usual mode of travel to work and a variety of socio-demographic characteristics. Using geographic information system (GIS) software, 30 exposure variables were produced capturing characteristics of areas around participants' homes and workplaces and their shortest modelled routes to work. Associations between usual mode of travel to work and personal and environmental characteristics were investigated using multinomial logistic regression.Of the 1124 respondents, 50% reported cycling or walking as their usual mode of travel to work. In adjusted analyses, home-work distance was strongly associated with mode choice, particularly for walking. Lower odds of walking or cycling rather than driving were associated with a less frequent bus service (highest versus lowest tertile: walking OR 0.61 [95% CI 0.20–1.85]; cycling OR 0.43 [95% CI 0.23–0.83]), low street connectivity (OR 0.22, [0.07–0.67]; OR 0.48 [0.26–0.90]) and free car parking at work (OR 0.24 [0.10–0.59]; OR 0.55 [0.32–0.95]). Participants were less likely to cycle if they had access to fewer destinations (leisure facilities, shops and schools) close to work (OR 0.36 [0.21–0.62]) and a railway station further from home (OR 0.53 [0.30–0.93]). Covariates strongly predicted travel mode (pseudo r-squared 0.74).Potentially modifiable environmental characteristics, including workplace car parking, street connectivity and access to public transport, are associated with travel mode choice, and could be addressed as part of transport policy and infrastructural interventions to promote active commuting

Quantitative Understanding of Probabilistic Behavior of Living Cells Operated by Vibrant Intracellular Networks

For quantitative understanding of probabilistic behaviors of living cells, it is essential to construct a correct mathematical description of intracellular networks interacting with complex cell environments, which has been a formidable task. Here, we present a novel model and stochastic kinetics for an intracellular network interacting with hidden cell environments, employing a complete description of cell state dynamics and its coupling to the system network. Our analysis reveals that various environmental effects on the product number fluctuation of intracellular reaction networks can be collectively characterized by Laplace transform of the time-correlation function of the product creation rate fluctuation with the Laplace variable being the product decay rate. On the basis of the latter result, we propose an efficient method for quantitative analysis of the chemical fluctuation produced by intracellular networks coupled to hidden cell environments. By applying the present approach to the gene expression network, we obtain simple analytic results for the gene expression variability and the environment-induced correlations between the expression levels of mutually noninteracting genes. The theoretical results compose a unified framework for quantitative understanding of various gene expression statistics observed across a number of different systems with a small number of adjustable parameters with clear physical meanings.open1143sciescopu

Nurses in advanced roles as a strategy for equitable access to healthcare in the WHO Western Pacific region: a mixed methods study

BackgroundThe Western Pacific region constitutes one-quarter of the world's population and has diverse health needs. While dialogue on and promotion of advanced practice nurses are ongoing, this study investigated the current responsibilities of nurses in advanced roles, future healthcare needs, and the implications of these components for nurses' professional development within the Western Pacific region.MethodsThis study employed three phases, a descriptive survey on the current status of nurses in advanced roles in the Western Pacific region, followed by a Delphi survey, and exploratory interviews. A total of 55 national experts with clinical, academic, and/or government-related backgrounds from 18 countries participated from December 2017 - December 2018. The descriptive survey via email to identify the status of nurses in advanced roles and a working definition was developed. This formed the basis for the Delphi survey, which identified key barriers and challenges for enhancing the development of nurses in advanced roles within the country (round 1) and for the region (rounds 2 and 3). Lastly, semi-structured individual interviews were conducted to identify strategies for establishing nurses in advanced roles to improve equitable access to healthcare.ResultsThirty-seven roles and characteristics were identified and categorized for nurses performing advanced roles. Emergency care, critical care, elderly health, child health, and rural/remote communities were identified as fields with particular need for nurses in advanced roles in the Western Pacific region. Providing effective services, influencing government leadership, and advocating for health system sustainability were deemed necessary to improve equitable healthcare access. We found that nurses in advanced roles are not limited to clinical tasks within the hospital but are poised for active participation in primary healthcare, education/teaching, professional leadership, quality management, and research.ConclusionsDemand for nurses in advanced roles is high in the Western Pacific region and 15 items were identified across five core strategic areas to enhance development of nurses in advanced roles. Governmental-level recommendations include establishing legislative protection, improving systems for remuneration, strengthening supportive channels, and conducting national needs assessments

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis

Improving smoking cessation care in pregnancy at Aboriginal Medical Services: 'ICAN QUIT in Pregnancy' step-wedge cluster randomised study

Objectives This study aimed to examine the impact of the ‘ICAN QUIT in Pregnancy’ intervention on individual health providers (HPs) smoking cessation care (SCC) knowledge, attitudes and practices in general, and specifically regarding nicotine replacement therapy (NRT) prescription. Design Step-wedge clustered randomised controlled study. HPs answered a preintervention and 1–6 months postintervention survey. Setting Six Aboriginal Medical Services (AMSs) in three states of Australia. Participants All HPs were invited to participate. Of 93 eligible, 50 consented (54%), 45 completed the presurvey (90%) and 20 the post (40%). Intervention Included three 1-hour webinar sessions, educational resource package and free oral NRT. Outcomes HPs knowledge was measured using two composite scores—one from all 24 true/false statements, and one from 12 NRT-specific statements. Self-assessment of 22 attitudes to providing SCC were measured using a five-point Likert scale (Strongly disagree to Strongly agree). Two composite mean scores were calculated—one for 15 general SCC attitudes, and one for 7 NRT-specific attitudes. Self-reported provision of SCC components was measured on a five-point Likert scale (Never to Always). Feasibility outcomes, and data collected on the service and patient level are reported elsewhere. Results Mean knowledge composite scores improved from pre to post (78% vs 84% correct, difference 5.95, 95%CI 1.57 to 10.32). Mean NRT-specific knowledge composite score also improved (68% vs 79% correct, difference 9.9, 95%CI 3.66 to 16.14). Mean attitude composite score improved (3.65 (SD 0.4) to 3.87 (SD 0.4), difference 0.23, 95%CI 0.05 to 0.41). Mean NRT-specific attitudes composite score also improved (3.37 (SD 0.6) to 3.64 (SD 0.7), difference 0.36, 95%CI 0.13 to 0.6). Selfreported practices were unchanged, including prescribing NRT. Conclusions A multicomponent culturally sensitive intervention in AMSs was feasible, and might improve HPs provision of SCC to pregnant Aboriginal women. Changes in NRT prescription rates may require additional intensive measures