A systems approach towards remote health-monitoring in older adults: Introducing a zero-interaction digital exhaust.

Using connected sensing devices to remotely monitor health is a promising way to help transition healthcare from a rather reactive to a more precision medicine oriented proactive approach, which could be particularly relevant in the face of rapid population ageing and the challenges it poses to healthcare systems. Sensor derived digital measures of health, such as digital biomarkers or digital clinical outcome assessments, may be used to monitor health status or the risk of adverse events like falls. Current research around such digital measures has largely focused on exploring the use of few individual measures obtained through mobile devices. However, especially for long-term applications in older adults, this choice of technology may not be ideal and could further add to the digital divide. Moreover, large-scale systems biology approaches, like genomics, have already proven beneficial in precision medicine, making it plausible that the same could also hold for remote-health monitoring. In this context, we introduce and describe a zero-interaction digital exhaust: a set of 1268 digital measures that cover large parts of a person's activity, behavior and physiology. Making this approach more inclusive of older adults, we base this set entirely on contactless, zero-interaction sensing technologies. Applying the resulting digital exhaust to real-world data, we then demonstrate the possibility to create multiple ageing relevant digital clinical outcome assessments. Paired with modern machine learning, we find these assessments to be surprisingly powerful and often on-par with mobile approaches. Lastly, we highlight the possibility to discover novel digital biomarkers based on this large-scale approach

Breathomics can discriminate between anti IgE-treated and non-treated severe asthma adults

Rationale: Omalizumab, an anti-IgE monoclonal antibody, is indicated in adults with severe persistent allergic asthma. Exhaled molecular markers can provide phenotypic information in asthma. Objectives: Determine whether adults with severe asthma on omalizumab (anti-IgE+) have a different breathprint compared with those who were not on anti-IgE therapy (anti-IgE-) as assessed by eNoses and gas chromatography/mass spectrometry (GC/MS) (breathomics). Methods: This was a cross-sectional analysis of the U- BIOPRED adult cohort. Severe asthma was defined by IMI-criteria [Bel, Thorax 2011]. Anti-IgE+ patients were on a regular treatment with s.c. omalizumab (150-375 mg) every 2-4 weeks. Exhaled volatile compounds trapped on adsorption tubes were analysed by a centralized eNose platform (Owlstone Lonestar, two Cyranose 320, Comon Invent, Tor Vergata TEN), including a total of 190 sensors, and GC/MS. Recursive feature elimination (http://topepo.github.io/caret/rfe.html) was used for feature selection and random forests, more robust to overfitting, for classification. Results: 9 anti- IgE+ (females/males 2/7, age 52.6±16.3 years, mean±SD, 1/2/6 current/ex/nonsmokers, pre-bronchodilator FEV1 70.6±21.1% predicted value) and 30 anti-IgE- patients (18/12 females/males, age 53.2±14.2 years, 0/16/14 current/ex/nonsmokers, pre-bronchodilator FEV1 59.6±30.7% predicted value) were studied. Conclusions: Preliminary results suggest that breathomics can distinguish between anti-IgE+ and anti-IgE- severe asthma patients

Methodological considerations for large-scale breath analysis studies : lessons from the U-BIOPRED severe asthma project

Methods for breath sampling and analysis require robust quality assessment to minimise the risk of false discoveries. Planning large-scale multi-site breath metabolite profiling studies also requires careful consideration of systematic and random variation as a result of sampling and analysis techniques. In this study we use breath sample data from the recent U-BIOPRED cohort to evaluate and discuss some important methodological considerations such as batch variation and correction, variation between sites, storage and transportation, as well as inter-instrument analytical differences. Based on this we provide a summary of recommended best practices for new large scale multi-site studies

Microbial volatiles as diagnostic biomarkers of bacterial lung infection in mechanically ventilated patients.

BackgroundEarly and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as non-invasive biomarkers of infection to support clinical diagnosis.MethodsIn this study, we investigated the diagnostic potential of in vitro confirmed mVOCs in the exhaled breath of patients under mechanically ventilation from the BreathDx study. Samples were analysed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS).ResultsPathogens from bronchoalveolar lavage (BAL) cultures were identified in 45/89 patients and S. aureus was the most commonly identified pathogen (n = 15). Out of 19 mVOCs detected in the in vitro culture headspace of four common respiratory pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli), 14 were found in exhaled breath samples. Higher concentrations of two mVOCs were found in the exhaled breath of patients infected with S. aureus compared to those without (3-methylbutanal p ConclusionsThis study demonstrates the capability of using mVOCs to detect the presence of specific pathogen groups with potential to support clinical diagnosis. Although not all mVOCs were found in patient samples within this small pilot study, further targeted and qualitative investigation is warranted using multi-centre clinical studies

Contact-free sensor signals as a new digital biomarker for cardiovascular disease: chances and challenges

Multiple sensor systems are used to monitor physiological parameters, activities of daily living and behaviour. Digital biomarkers can be extracted and used as indicators for health and disease. Signal acquisition is either by object sensors, wearable sensors, or contact-free sensors including cameras, pressure sensors, non-contact capacitively coupled electrocardiogram (cECG), radar, and passive infrared motion sensors. This review summarizes contemporary knowledge of the use of contact-free sensors for patients with cardiovascular disease and healthy subjects following the PRISMA declaration. Chances and challenges are discussed. Thirty-six publications were rated to be of medium (31) or high (5) relevance. Results are best for monitoring of heart rate and heart rate variability using cardiac vibration, facial camera, or cECG; for respiration using cardiac vibration, cECG, or camera; and for sleep using ballistocardiography. Early results from radar sensors to monitor vital signs are promising. Contact-free sensors are little invasive, well accepted and suitable for long-term monitoring in particular in patient’s homes. A major problem are motion artefacts. Results from long-term use in larger patient cohorts are still lacking, but the technology is about to emerge the market and we can expect to see more clinical results in the near future

First order reversal curve analysis on NdFeB nanocomposite ribbons subjected to Joule heating treatments

Amorphous precursors with composition Nd4.5Fe72−xCo3+xCr2Al1B17.5 (x = 0, 2, 7, 12) were thermally treated by the Joule heating technique with a linearly varying electrical current. The crystallization kinetics was followed by monitoring the resistance of the ribbons during the heating up to the final applied current. Crystallized nanostructured phases coexist with an amorphous matrix, as it was observed by means of Mössbauer Spectroscopy and X-ray diffraction. The irreversible magnetic response of the Joule heated ribbons was analyzed by the First Order Reversal Curves (FORC) diagram technique. For the optimal treatments, associated with the higher maximum energy products for each sample composition, it was found that the main interaction is of a strongly dipolar characteristic. Over annealed samples show a FORC diagram that gives into account of softening, due to grain growth, for those phases precipitated at the first crystallization stage. When it is measured at 20 K, the hardest magnetic sample (Fe = 72 at.%, Co = 3 at.%, Ifinal = 0.5 A), exhibits a diagram with characteristics corresponding to dipolar interactions of soft phases. This fact is consistent with an enhancement of the exchange length due to the increase in the soft phase stiffness as it is expected at low temperatures.Fil: Pampillo, Laura Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long". Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long"; ArgentinaFil: Saccone, Fabio Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long". Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long"; ArgentinaFil: Knobel, Marcelo. Universidade Estadual de Campinas; BrasilFil: Sirkin, Hugo Ricardo Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long". Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long"; Argentin

Real-World Consumer-Grade Sensor Signal Alignment Procedure Applied to High-Noise ECG to BCG Signal Synchronization *

In recent years, consumer-grade sensors that measure health relevant physiological signals have become widely available and are increasingly used by consumers and researchers alike. While this allows for multiple novel, potentially highly beneficial, large-scale health monitoring applications, quality of these data streams is oftentimes suboptimal. This makes alignment of different high-frequency data streams from multiple, non-connected sensors, a difficult task. In this work we describe a noise-robust framework to align high-frequency signals from different sensors, that share some underlying characteristic, obtained in a free-living, non-clinical, home environment. We demonstrate the approach on the basis of a single-lead, medical-grade, mobile electrocardiography device and a consumer-grade sleep sensor that allows for ballistocardiography. Both commercially available sensors measure the physiological process of a heartbeat. We show, on the basis of real-world data with multiple people and sensors, that the two highly noisy and sometimes dissimilar signals could in most cases be aligned with considerable precision. As a result, we could reduce mean heartbeat peak-to-peak difference by 58.1% on average and increase signal correlation by 0.40 on average

Photo-substitution reactions of perylene red dyes

Irradiation of Lumogen Red 305 (3) in ethyl acetate with intense blue LED light led to very slow bleaching, showing a high photochemical stability. However, irradiation in ethanol led to the formation of a low yield product in which one of the phenoxy groups is substituted by an acetoxy group, the oxidized form of an ethoxy group. This reaction product was only formed in the presence of blue light and oxygen. Adding a small amount of acetic acid to the solutions resulted in a much higher yield of the product, indicating a possible photo oxidation of ethanol to acetic acid during the process in this solvent. A similar dye (5) containing less phenoxy side groups than Lumogen Red 305 showed the same reaction although the product formed showed lower chemical stability. The photo-substitution of phenoxy groups by acetoxy groups is a new reaction. The results are used to discuss the structural effects on the stability of these type of fluorescent dyes under irradiation conditions, potential reaction mechanisms and the possibility of using the photochemical transformations for preparative purposes