Technical challenges related to implementation of a formula one real time data acquisition and analysis system in a paediatric intensive care unit

Most existing, expert monitoring systems do not provide the real time continuous analysis of the monitored physiological data that is necessary to detect transient or combined vital sign indicators nor do they provide long term storage of the data for retrospective analyses. In this paper we examine the feasibility of implementing a long term data storage system which has the ability to incorporate real-time data analytics, the system design, report the main technical issues encountered, the solutions implemented and the statistics of the data recorded. McLaren Electronic Systems expertise used to continually monitor and analyse the data from F1 racing cars in real time was utilised to implement a similar real-time data recording platform system adapted with real time analytics to suit the requirements of the intensive care environment. We encountered many technical (hardware and software) implementation challenges. However there were many advantages of the system once it was operational. They include: (1) The ability to store the data for long periods of time enabling access to historical physiological data. (2) The ability to alter the time axis to contract or expand periods of interest. (3) The ability to store and review ECG morphology retrospectively. (4) Detailed post event (cardiac/respiratory arrest or other clinically significant deteriorations in patients) data can be reviewed clinically as opposed to trend data providing valuable clinical insight. Informed mortality and morbidity reviews can be conducted. (5) Storage of waveform data capture to use for algorithm development for adaptive early warning systems. Recording data from bed-side monitors in intensive care/wards is feasible. It is possible to set up real time data recording and long term storage systems. These systems in future can be improved with additional patient specific metrics which predict the status of a patient thus paving the way for real time predictive monitoring

COMPASS identifies T-cell subsets correlated with clinical outcomes.

Advances in flow cytometry and other single-cell technologies have enabled high-dimensional, high-throughput measurements of individual cells as well as the interrogation of cell population heterogeneity. However, in many instances, computational tools to analyze the wealth of data generated by these technologies are lacking. Here, we present a computational framework for unbiased combinatorial polyfunctionality analysis of antigen-specific T-cell subsets (COMPASS). COMPASS uses a Bayesian hierarchical framework to model all observed cell subsets and select those most likely to have antigen-specific responses. Cell-subset responses are quantified by posterior probabilities, and human subject-level responses are quantified by two summary statistics that describe the quality of an individual's polyfunctional response and can be correlated directly with clinical outcome. Using three clinical data sets of cytokine production, we demonstrate how COMPASS improves characterization of antigen-specific T cells and reveals cellular 'correlates of protection/immunity' in the RV144 HIV vaccine efficacy trial that are missed by other methods. COMPASS is available as open-source software

Microbial Symbionts in Insects Influence Down-Regulation of Defense Genes in Maize

Diabrotica virgifera virgifera larvae are root-feeding insects and significant pests to maize in North America and Europe. Little is known regarding how plants respond to insect attack of roots, thus complicating the selection for plant defense targets. Diabrotica virgifera virgifera is the most successful species in its genus and is the only Diabrotica beetle harboring an almost species-wide Wolbachia infection. Diabrotica virgifera virgifera are infected with Wolbachia and the typical gut flora found in soil-living, phytophagous insects. Diabrotica virgifera virgifera larvae cannot be reared aseptically and thus, it is not possible to observe the response of maize to effects of insect gut flora or other transient microbes. Because Wolbachia are heritable, it is possible to investigate whether Wolbachia infection affects the regulation of maize defenses. To answer if the success of Diabrotica virgifera virgifera is the result of microbial infection, Diabrotica virgifera virgifera were treated with antibiotics to eliminate Wolbachia and a microarray experiment was performed. Direct comparisons made between the response of maize root tissue to the feeding of antibiotic treated and untreated Diabrotica virgifera virgifera show down-regulation of plant defenses in the untreated insects compared to the antibiotic treated and control treatments. Results were confirmed via QRT-PCR. Biological and behavioral assays indicate that microbes have integrated into Diabrotica virgifera virgifera physiology without inducing negative effects and that antibiotic treatment did not affect the behavior or biology of the insect. The expression data and suggest that the pressure of microbes, which are most likely Wolbachia, mediate the down-regulation of many maize defenses via their insect hosts. This is the first report of a potential link between a microbial symbiont of an insect and a silencing effect in the insect host plant. This is also the first expression profile for a plant attacked by a root-feeding insect

Design, Analysis and Testing of a Novel Mitral Valve for Transcatheter Implantation

Mitral regurgitation is a common mitral valve dysfunction which may lead to heart failure. Because of the rapid aging of the population, conventional surgical repair and replacement of the pathological valve are often unsuitable for about half of symptomatic patients, who are judged high-risk. Transcatheter valve implantation could represent an effective solution. However, currently available aortic valve devices are inapt for the mitral position. This paper presents the design, development and hydrodynamic assessment of a novel bi-leaflet mitral valve suitable for transcatheter implantation. The device consists of two leaflets and a sealing component made from bovine pericardium, supported by a self-expanding wireframe made from superelastic NiTi alloy. A parametric design procedure based on numerical simulations was implemented to identify design parameters providing acceptable stress levels and maximum coaptation area for the leaflets. The wireframe was designed to host the leaflets and was optimised numerically to minimise the stresses for crimping in an 8 mm sheath for percutaneous delivery. Prototypes were built and their hydrodynamic performances were tested on a cardiac pulse duplicator, in compliance with the ISO5840-3:2013 standard. The numerical results and hydrodynamic tests show the feasibility of the device to be adopted as a transcatheter valve implant for treating mitral regurgitation

Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants?

Introduction: Many of the DNA sequence variants identified in the breast cancer susceptibility gene BRCA1 remain unclassified in terms of their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance of such variants, but analysis of the comparative value of these methods for classifying all sequence variants has been limited. Methods: We have compared the results from multifactorial likelihood analysis with those from several functional analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V. Results: Our results show that multifactorial likelihood analysis, which incorporates sequence conservation, co-inheritance, segregation, and tumour immunohistochemical analysis, may improve classification of variants. For A1708E, previously shown to be functionally compromised, analysis of oestrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly strengthened the prediction of pathogenicity, giving a posterior probability of pathogenicity of 99%. For G1738R, shown to be functionally defective in this study, immunohistochemistry analysis confirmed previous findings of inconsistent 'BRCA1-like' phenotypes for the two tumours studied, and the posterior probability for this variant was 96%. The posterior probabilities of R1699Q and A1708V were 54% and 69%, respectively, only moderately suggestive of increased risk. Interestingly, results from functional analyses suggest that both of these variants have only partial functional activity. R1699Q was defective in foci formation in response to DNA damage and displayed intermediate transcriptional transactivation activity but showed no evidence for centrosome amplification. In contrast, A1708V displayed an intermediate transcriptional transactivation activity and a normal foci formation response in response to DNA damage but induced centrosome amplification. Conclusion: These data highlight the need for a range of functional studies to be performed in order to identify variants with partially compromised function. The results also raise the possibility that A1708V and R1699Q may be associated with a low or moderate risk of cancer. While data pooling strategies may provide more information for multifactorial analysis to improve the interpretation of the clinical significance of these variants, it is likely that the development of current multifactorial likelihood approaches and the consideration of alternative statistical approaches will be needed to determine whether these individually rare variants do confer a low or moderate risk of breast cancer

Trypanosoma cruzi Epimastigotes Are Able to Store and Mobilize High Amounts of Cholesterol in Reservosome Lipid Inclusions

Reservosomes are lysosome-related organelles found in Trypanosoma cruzi epimastigotes. They represent the last step in epimastigote endocytic route, accumulating a set of proteins and enzymes related to protein digestion and lipid metabolism. The reservosome matrix contains planar membranes, vesicles and lipid inclusions. Some of the latter may assume rectangular or sword-shaped crystalloid forms surrounded by a phospholipid monolayer, resembling the cholesterol crystals in foam cells.Using Nile Red fluorimetry and fluorescence microscopy, as well as electron microscopy, we have established a direct correlation between serum concentration in culture medium and the presence of crystalloid lipid inclusions. Starting from a reservosome purified fraction, we have developed a fractionation protocol to isolate lipid inclusions. Gas-chromatography mass-spectrometry (GC-MS) analysis revealed that lipid inclusions are composed mainly by cholesterol and cholesterol esters. Moreover, when the parasites with crystalloid lipid-loaded reservosomes were maintained in serum free medium for 48 hours the inclusions disappeared almost completely, including the sword shaped ones.Taken together, our results suggest that epimastigote forms of T. cruzi store high amounts of neutral lipids from extracellular medium, mostly cholesterol or cholesterol esters inside reservosomes. Interestingly, the parasites are able to disassemble the reservosome cholesterol crystalloid inclusions when submitted to serum starvation

Health Journalism Internships: A Social Marketing Strategy to Address Health Disparities

The USA seeks to eliminate health disparities by stimulating the rapid uptake of health-promoting behaviors within disadvantaged communities. A health journalism internship incorporates social marketing strategies to increase communities' access to cancer information, while helping the interns who are recruited from underrepresented communities gain admission to top graduate schools. Interns are taught basic health journalism skills that enable them to create immediate streams of cancer-related press releases for submission to community newspapers. Interns are charged with the social responsibility of continuing this dissemination process throughout their careers. Intermediate outcomes are measured as mediators of distal behavioral change goals

PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN 74418480]

BACKGROUND: In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3°C (95% CI: 0.1–0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. METHODS/DESIGN: Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one

Bridge to the future: Important lessons from 20 years of ecosystem observations made by the OzFlux network

In 2020, the Australian and New Zealand flux research and monitoring network, OzFlux, celebrated its 20th anniversary by reflecting on the lessons learned through two decades of ecosystem studies on global change biology. OzFlux is a network not only for ecosystem researchers, but also for those ‘next users’ of the knowledge, information and data that such networks provide. Here, we focus on eight lessons across topics of climate change and variability, disturbance and resilience, drought and heat stress and synergies with remote sensing and modelling. In distilling the key lessons learned, we also identify where further research is needed to fill knowledge gaps and improve the utility and relevance of the outputs from OzFlux. Extreme climate variability across Australia and New Zealand (droughts and flooding rains) provides a natural laboratory for a global understanding of ecosystems in this time of accelerating climate change. As evidence of worsening global fire risk emerges, the natural ability of these ecosystems to recover from disturbances, such as fire and cyclones, provides lessons on adaptation and resilience to disturbance. Drought and heatwaves are common occurrences across large parts of the region and can tip an ecosystem\u27s carbon budget from a net CO2 sink to a net CO2 source. Despite such responses to stress, ecosystems at OzFlux sites show their resilience to climate variability by rapidly pivoting back to a strong carbon sink upon the return of favourable conditions. Located in under-represented areas, OzFlux data have the potential for reducing uncertainties in global remote sensing products, and these data provide several opportunities to develop new theories and improve our ecosystem models. The accumulated impacts of these lessons over the last 20 years highlights the value of long-term flux observations for natural and managed systems. A future vision for OzFlux includes ongoing and newly developed synergies with ecophysiologists, ecologists, geologists, remote sensors and modellers