Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis

Objective: The recent Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial suggested that implantable cardioverter defibrillators (ICDs) do not reduce overall mortality in patients with non-ischaemic cardiomyopathy (NICM), despite reducing sudden cardiac death. We performed an updated meta-analysis to examine the impact of ICD therapy on mortality in NICM patients. Methods: A systematic search for studies that examined the effect of ICDs on outcomes in NICM was performed. Our analysis compared patients randomised to an ICD with those randomised to no ICD, and examined the endpoint of overall mortality. Results: Six primary prevention trials and two secondary prevention trials were identified that met the pre-specified search criteria. Using a fixed-effects model, analysis of primary prevention trials revealed a reduction in overall mortality with ICD therapy (RR 0.76, 95% CI 0.65 to 0.91). Conclusions: Although our updated meta-analysis demonstrates a survival benefit of ICD therapy, the effect is substantively weakened by the inclusion of the DANISH trial—which is both the largest and most recent of the analysed trials—indicating that the residual pooled benefit of ICDs may reflect the risk of sudden death in older trials which included patients treated sub-optimally by contemporary standards. As such, these data must be interpreted cautiously. The results of the DANISH trial emphasise that there is no ‘one size fits all’ indication for primary prevention ICDs in NICM patients, and clinicians must consider age and comorbidity on an individual basis when determining whether a defibrillator is appropriate

Prediction-based classification for longitudinal biomarkers

Assessment of circulating CD4 count change over time in HIV-infected subjects on antiretroviral therapy (ART) is a central component of disease monitoring. The increasing number of HIV-infected subjects starting therapy and the limited capacity to support CD4 count testing within resource-limited settings have fueled interest in identifying correlates of CD4 count change such as total lymphocyte count, among others. The application of modeling techniques will be essential to this endeavor due to the typically nonlinear CD4 trajectory over time and the multiple input variables necessary for capturing CD4 variability. We propose a prediction-based classification approach that involves first stage modeling and subsequent classification based on clinically meaningful thresholds. This approach draws on existing analytical methods described in the receiver operating characteristic curve literature while presenting an extension for handling a continuous outcome. Application of this method to an independent test sample results in greater than 98% positive predictive value for CD4 count change. The prediction algorithm is derived based on a cohort of $n=270$ HIV-1 infected individuals from the Royal Free Hospital, London who were followed for up to three years from initiation of ART. A test sample comprised of $n=72$ individuals from Philadelphia and followed for a similar length of time is used for validation. Results suggest that this approach may be a useful tool for prioritizing limited laboratory resources for CD4 testing after subjects start antiretroviral therapy.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS326 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A high resolution mid-infrared survey of water emission from protoplanetary disks

We present the largest survey of spectrally resolved mid-infrared water emission to date, with spectra for 11 disks obtained with the Michelle and TEXES spectrographs on Gemini North. Water emission is detected in 6 of 8 disks around classical T Tauri stars. Water emission is not detected in the transitional disks SR 24 N and SR 24 S, in spite of SR 24 S having pre-transitional disk properties like DoAr 44, which does show water emission (Salyk et al. 2015). With R~100,000, the TEXES water spectra have the highest spectral resolution possible at this time, and allow for detailed lineshape analysis. We find that the mid-IR water emission lines are similar to the "narrow component" in CO rovibrational emission (Banzatti & Pontoppidan 2015), consistent with disk radii of a few AU. The emission lines are either single peaked, or consistent with a double peak. Single-peaked emission lines cannot be produced with a Keplerian disk model, and may suggest that water participates in the disk winds proposed to explain single-peaked CO emission lines (Bast et al. 2011, Pontoppidan et al. 2011). Double-peaked emission lines can be used to determine the radius at which the line emission luminosity drops off. For HL Tau, the lower limit on this measured dropoff radius is consistent with the 13 AU dark ring (ALMA partnership et al. 2015). We also report variable line/continuum ratios from the disks around DR Tau and RW Aur, which we attribute to continuum changes and line flux changes, respectively. The reduction in RW Aur line flux corresponds with an observed dimming at visible wavelengths (Rodriguez et al. 2013).Comment: To appear in the Astrophysical Journa

The dawn phenomenon in type 2 diabetes: How to assess it in clinical practice?

International audienceAIM : The study was aimed at determining whether the dawn phenomenon in type 2 diabetes (T2D) can be predicted and quantified using simple and easily accessible glucose determinations.METHODS : A total of 210 non-insulin-treated persons with T2D underwent continuous glucose monitoring (CGM). The dawn phenomenon was quantified as the absolute increment from the nocturnal glucose nadir to the pre-breakfast value (Δdawn, mg/dL). Pre-lunch (preL) and pre-dinner (preD) glucose, and their averaged values (preLD), were compared with the nocturnal nadir. These pre-meal values were subtracted from the pre-breakfast values. The differences obtained (Δpre-mealL, Δpre-meal D and Δpre-meal LD) were correlated with Δdawn values. The receiver operating characteristic (ROC) curve was used to select the optimal Δpre-meal value that best predicted a dawn phenomenon, set at a threshold of 20mg/dL.RESULTS : All pre-meal glucose levels and differences from pre-breakfast values (Δpre-meal) significantly correlated (P<0.0001) with the nocturnal nadir and Δdawn values, respectively. The strongest correlations were observed for the parameters averaged at preL and preD time points: r=0.83 for preLD and r=0.58 for Δpre-meal LD. ROC curve analysis indicated that the dawn phenomenon at a threshold of 20mg/dL can be significantly predicted by a Δpre-meal LD cut off value of 10mg/dL. The relationship between Δdawn (Y, mg/dL) and Δpre-meal LD (X, mg/dL) was Y=0.49 X+15.CONCLUSION : The self-monitoring of preprandial glucose values at the three main mealtimes can predict the presence/absence of the dawn phenomenon, and permits reliable assessment of its magnitude without requiring continuous overnight glucose monitoring

A Lagrangian analysis of the impact of transport and transformation on the ozone stratification observed in the free troposphere during the ESCOMPTE campaign

The ozone variability observed by tropospheric ozone lidars during the ESCOMPTE campaign is analyzed by means of a hybrid-Lagrangian modeling study. Transport processes responsible for the formation of ozone-rich layers are identified using a semi-Lagrangian analysis of mesoscale simulations to identify the planetary boundary layer (PBL) footprint in the free troposphere. High ozone concentrations are related to polluted air masses exported from the Iberian PBL. The chemical composition of air masses coming from the PBL and transported in the free troposphere is evaluated using a Lagrangian chemistry model. The initial concentrations are provided by a model of chemistry and transport. Different scenarios are tested for the initial conditions and for the impact of mixing with background air in order to perform a quantitative comparison with the lidar observations. For this meteorological situation, the characteristic mixing time is of the order of 2 to 6 days depending on the initial conditions. Ozone is produced in the free troposphere within most air masses exported from the Iberian PBL at an average rate of 0.2 ppbv h^&minus;1, with a maximum ozone production of 0.4 ppbv h^&minus;1. Transport processes from the PBL are responsible for an increase of 13.3 ppbv of ozone concentrations in the free troposphere compared to background levels; about 45% of this increase is attributed to in situ production during the transport rather than direct export of ozone

Predictors of poor sleep quality among Lebanese university students: association between evening typology, lifestyle behaviors, and sleep habits

Adequate, good night sleep is fundamental to well-being and is known to be influenced by myriad biological and environmental factors. Given the unavailability of sleep data about Lebanon, the cultural shifts and socioeconomic pressures that have affected many aspects of society, particularly for students and working adults, as well as our understanding of sleep in university students in other countries, we conducted a national study to assess sleep quality and factors contributing to sleep and general health in a culture-specific context. A self-filled questionnaire, inquiring about sociodemographics, health-risk behaviors, personal health, and evaluating sleep quality and chronotype using standard scales was completed by 540 students at private and public universities in Lebanon. Overall, they reported sleeping 7.95±1.34 hours per night, although 12.3% reported sleeping <6.5 hours and more than half scored in the poor-sleeper category on the Pittsburgh Sleep Quality Index (PSQI). Sleep timing differed markedly between weekdays and weekends, with bedtimes and wake-up times delayed by 1.51 and 2.43 hours, respectively, on weekends. While most scored in the “neither type” category on the Morningness–Eveningness Questionnaire (MEQ), 24.5% were evening types and 7.3% were morning types. MEQ score was significantly correlated with smoking behavior and daily study onset, as well as with PSQI score, with eveningness associated with greater number of cigarettes, later study times, and poor sleep. We conclude that the prevalence of poor sleep quality among Lebanese university students is associated with reduced sleep duration and shifts in sleep timing between weekdays and weekends, especially among evening types. While chronotype and certain behavioral choices interact to affect sleep dimensions and quality, raising awareness about the importance of obtaining adequate nighttime sleep on daily performance and avoiding risky behaviors may help Lebanese students make better choices in school and work schedules

Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

Objectives: The resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care. Methods: We studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI. Using deep sequencing, resistance-associated mutations (RAMs) were detected in stored samples collected at tenofovir introduction (T0) and after a median of 4.0 years (T1). Results: At T0, 19/87 (21.8%) subjects showed a detectable viral load and 8/87 (9.2%) had one or more major NNRTI RAMs, whereas 82/87 (94.3%) retained full tenofovir susceptibility. At T1, 79/87 (90.8%) subjects remained on NNRTI-based ART, 5/87 (5.7%) had introduced lopinavir/ritonavir due to immunological failure, and 3/87 (3.4%) had interrupted ART. Whilst 68/87 (78.2%) subjects maintained or achieved virological suppression between T0 and T1, a detectable viral load with NNRTI RAMs at T0 predicted lack of virological suppression at T1. Each treatment interruption, usually reflecting unavailability of the dispensary, doubled the risk of T1 viraemia. Tenofovir, lamivudine and efavirenz selected for K65R, K70E/T, L74I/V and Y115F, alongside M184V and multiple NNRTI RAMs; this resistance profile was accompanied by high viral loads and low CD4 cell counts. Conclusions: Viraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission

Relational coupling of multiple streams: The case of COVID‐19 infections in German abattoirs

After a series of COVID-19 outbreaks among employees in the German meat-processing industry, the Work Safety Control Act protecting these workers made it on the government's agenda in July 2020. From a Multiple Streams perspective, local corona hotspots may be understood as policy windows for introducing respective measures. However, this alone is not sufficient to explain agenda setting. This study investigates the coupling of streams within policy windows. Introducing the notion of relational coupling to the MSF research agenda, discourse network analysis provides a new methodology to reveal entrepre-neurial activities. Studying the German mass media discourse on the issue identifies two stages: (1) An initial problem broker-age without coupling of core policies, followed by (2) a coupling across all streams based on a focusing event. We argue that relational coupling allows for an enhanced understanding of agenda setting