Atrial fibrillation (AF) is a cardiac rhythm disorder associated with increased morbidity and mortality. It is the leading risk factor for cardioembolic stroke and its early detection is crucial in both primary and secondary stroke prevention. Continuous monitoring of cardiac rhythm is today possible thanks to consumer-grade wearable devices, enabling transformative diagnostic and patient management tools. Such monitoring is possible using low-cost easy-to-implement optical sensors that today equip the majority of wearables. These sensors record blood volume variations-a technology known as photoplethysmography (PPG)-from which the heart rate and other physiological parameters can be extracted to inform about user activity, fitness, sleep, and health. Recently, new wearable devices were introduced as being capable of AF detection, evidenced by large prospective trials in some cases. Such devices would allow for early screening of AF and initiation of therapy to prevent stroke. This review is a summary of a body of work on AF detection using PPG. A thorough account of the signal processing, machine learning, and deep learning approaches used in these studies is presented, followed by a discussion of their limitations and challenges towards clinical applications.npj Digital Medicine (2020) 3:3 ; https://doi.org/10.1038/s41746-019-0207-9 PHOTOPLETHYSMOGRAPHY PPG signal PPG waveform is generated during a cardiac cycle and typically measured at a peripheral site. Therefore, it is essentially a pulse pressure waveform that originates from the heart contraction and propagates through the vascular tree. As blood flow is controlled

In this study, we examined the effect of in vivo treatment of acutely SIV-infected Mamu-A*01+ rhesus macaques with IL-15. IL-15 treatment during acute infection increased viral set point by 3 logs and accelerated the development of simian AIDS in two of six animals with one developing early minimal lesion SIV meningoencephalitis. Although IL-15 induced a 2- to 3-fold increase in SIV-specific CD8+ T cell and NK cell numbers at peak viremia and reduced lymph node (LN) SIV-infected cells, this had no impact on peak viremia and did not lower viral set point. At viral set point, however, activated SIV-specific CD8+ T cells and NK cells were reduced in the blood of IL-15-treated animals and LN SIV-infected cells were increased. Week 30 LN from IL-15-treated animals had significantly increased Gag-specific CD8+ T cell numbers, whereas total cell, lymphocyte, and CD4+ T cell numbers were reduced. IL-15 treatment significantly reduced anti-SIV Ab concentrations at week 3 and viral set point. IL-15 increased Ki-67+CD4+ T cells at week 1 of treatment and reduced blood CCR5+ and CD45RA−CD62L− CD4+ T cells. The frequency of day 7 Ki-67+CD4+ T cells strongly correlated with viral set point. These findings suggest that CD4+ T cell activation during acute infection determines subsequent viral set point and IL-15 treatment by increasing such activation elevates viral set point. Finally, IL-15-treated acutely SIV-infected primates may serve as a useful model to investigate the poorly understood mechanisms that control viral set point and disease progression in HIV infection.

The role of Type I interferon (IFN) during pathogenic HIV and SIV infections remains unclear, with conflicting observations suggesting protective versus immunopathological effects. We therefore examined the effect of IFNα/β on T cell death and viremia in HIV infection. Ex vivo analysis of eight pro- and anti-apoptotic molecules in chronic HIV-1 infection revealed that pro-apoptotic Bak was increased in CD4+ T cells and correlated directly with sensitivity to CD95/Fas-mediated apoptosis and inversely with CD4+ T cell counts. Apoptosis sensitivity and Bak expression were primarily increased in effector memory T cells. Knockdown of Bak by RNA interference inhibited CD95/Fas-induced death of T cells from HIV-1-infected individuals. In HIV-1-infected patients, IFNα-stimulated gene expression correlated positively with ex vivo T cell Bak levels, CD95/Fas-mediated apoptosis and viremia and negatively with CD4+ T cell counts. In vitro IFNα/β stimulation enhanced Bak expression, CD95/Fas expression and CD95/Fas-mediated apoptosis in healthy donor T cells and induced death of HIV-specific CD8+ T cells from HIV-1-infected patients. HIV-1 in vitro sensitized T cells to CD95/Fas-induced apoptosis and this was Toll-like receptor (TLR)7/9- and Type I IFN-dependent. This sensitization by HIV-1 was due to an indirect effect on T cells, as it occurred in peripheral blood mononuclear cell cultures but not purified CD4+ T cells. Finally, peak IFNα levels and viral loads correlated negatively during acute SIV infection suggesting a potential antiviral effect, but positively during chronic SIV infection indicating that either the virus drives IFNα production or IFNα may facilitate loss of viral control. The above findings indicate stage-specific opposing effects of Type I IFNs during HIV-1 infection and suggest a novel mechanism by which these cytokines contribute to T cell depletion, dysregulation of cellular immunity and disease progression.

BackgroundNovel therapies aimed at modulating the autonomic nervous system, including thoracic epidural anesthesia (TEA), have been shown in small case series to be beneficial in treating medically refractory ventricular tachycardia (VT) storm. However, it is not clear when these options should be considered. We reviewed a multicenter experience with TEA in the management of VT storm to determine its optimal therapeutic use.Methods and ResultsData for 11 patients in whom TEA was instituted for VT storm between July 2005 and March 2016 were reviewed to determine the clinical characteristics, outcomes, and role in management. The clinical presentation was incessant VT in 7 (64%), with polymorphic VT in 3 (27%) and monomorphic VT in 8 (73%). The underlying conditions were nonischemic cardiomyopathy in 5 (45%), ischemic cardiomyopathy in 3 (27%), and hypertrophic cardiomyopathy, Brugada syndrome, and cardiac lipoma in 1 (9%) each. Five (45%) had a complete and 1 (9%) had a partial response to TEA; 4 of the complete responders had incessant VT. All 4 patients with a documented response to deep sedation demonstrated a complete response to TEA.ConclusionsMore than half of the patients with VT storm in our series responded to TEA. TEA may be effective and should be considered as a therapeutic option in patients with VT storm, especially incessant VT, who are refractory to initial management. Improvement in VT burden with deep sedation may suggest that sympathoexcitation plays a key role in perpetuating VT and predict a positive response to TEA.

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CMR can be performed safely in non-MRI-conditional CIEDs using a standardized protocol. Use of a wideband pulse sequence for LGE imaging yields a high rate of studies unaffected by artifact.

Poor air quality is often associated with hot weather, but the quantitative attribution of high temperatures on air quality remains unclear. In this study, the effect of elevated temperatures on air quality is investigated in Greater Sydney using January 2013, a period of extreme heat during which temperatures at times exceeded 40 • C, as a case study. Using observations from 17 measurement sites and the Weather Research and Forecasting Chemistry (WRF-Chem) model, we analyse the effect of elevated temperatures on ozone in Sydney by running a number of sensitivity studies in which:(1) the model is run with biogenic emissions generated by MEGAN and separately run with monthly average Model of Emissions of Gases and Aerosols from Nature ( MEGAN) biogenic emissions (for January 2013); (2) the model results from the standard run are compared with those in which average temperatures (for January 2013) are only applied to the chemistry; (3) the model is run using both averaged biogenic emissions and temperatures; and (4 and 5) the model is run with half and zero biogenic emissions. The results show that the impact on simulated ozone through the effect of temperature on reaction rates is similar to the impact via the effect of temperature on biogenic emissions and the relative impacts are largely additive when compared to the run in which both are averaged. When averaged across 17 sites in Greater Sydney, the differences between ozone simulated under standard and averaged model conditions are as high as 16 ppbv. Removing biogenic emissions in the model has the effect of removing all simulated ozone episodes during extreme heat periods, highlighting the important role of biogenic emissions in Australia, where Eucalypts are a key biogenic source.

We propose a new technique to prepare statistically-robust benchmarking data for evaluating chemical transport model meteorology and air quality parameters within the urban boundary layer. The approach employs atmospheric class-typing, using nocturnal radon measurements to assign atmospheric mixing classes, and can be applied temporally (across the diurnal cycle), or spatially (to create angular distributions of pollutants as a top-down constraint on emissions inventories). In this study only a short (<1-month) campaign is used, but grouping of the relative mixing classes based on nocturnal mean radon concentrations can be adjusted according to dataset length (i.e., number of days per category), or desired range of within-class variability. Calculating hourly distributions of observed and simulated values across diurnal composites of each class-type helps to: (i) bridge the gap between scales of simulation and observation, (ii) represent the variability associated with spatial and temporal heterogeneity of sources and meteorology without being confused by it, and (iii) provide an objective way to group results over whole diurnal cycles that separates ‘natural complicating factors’ (synoptic non-stationarity, rainfall, mesoscale motions, extreme stability, etc.) from problems related to parameterizations, or between-model differences. We demonstrate the utility of this technique using output from a suite of seven contemporary regional forecast and chemical transport models. Meteorological model skill varied across the diurnal cycle for all models, with an additional dependence on the atmospheric mixing class that varied between models. From an air quality perspective, model skill regarding the duration and magnitude of morning and evening “rush hour” pollution events varied strongly as a function of mixing class. Model skill was typically the lowest when public exposure would have been the highest, which has important implications for assessing potential health risks in new and rapidly evolving urban regions, and also for prioritizing the areas of model improvement for future applications.