Pathogen interference is the ability of one pathogen to alter the course and clinical outcomes of infection by another. With up to 3000 species of human pathogens the potential combinations are vast. These combinations operate within further immune complexity induced by infection with multiple persistent pathogens, and by the role which the human microbiome plays in maintaining health, immune function, and resistance to infection. All the above are further complicated by malnutrition in children and the elderly. Influenza vaccination offers a measure of protection for elderly individuals subsequently infected with influenza. However, all vaccines induce both specific and non-specific effects. The specific effects involve stimulation of humoral and cellular immunity, while the nonspecific effects are far more nuanced including changes in gene expression patterns and production of small RNAs which contribute to pathogen interference. Little is known about the outcomes of vaccinated elderly not subsequently infected with influenza but infected with multiple other non-influenza winter pathogens. In this review we propose that in certain years the specific antigen mix in the seasonal influenza vaccine inadvertently increases the risk of infection from other non-influenza pathogens. The possibility that vaccination could upset the pathogen balance, and that the timing of vaccination relative to the pathogen balance was critical to success, was proposed in 2010 but was seemingly ignored. Persons vaccinated early in the winter are more likely to experience higher pathogen interference. Implications to the estimation of vaccine effectiveness and influenza deaths are discussed.

Surface waves can be used to obtain a near-surface shear wave profile. The inverse problem is usually solved for the locally 1-D problem of a set of homogeneous horizontal elastic layers. The output is a set of shear velocity values for each layer in the profile. P-wave velocity profile can be estimated if higher modes and P-guided waves are used in the inversion scheme. Here, we use an exact acoustic solution to invert for the P-velocity profile in an elastic model with a decreasing constant vertical gradient of the squared P-wave slowness, bounded by a free surface on the top and a homogeneous halfspace at the bottom. The exact acoustic solution can be expressed in Airy functions and leads to a dispersion equation. We can invert several modes of the dispersion equation for the single gradient parameter of the squared P-wave slowness from elastic data. As a first test case, we invert for the P-wave velocity profile of synthetic 2-D isotropic elastic data with a small Vs/Vp-ratio, using the first two dispersive P-wave modes. The method does not require any picking and should be able to provide an initial model for full waveform inversion when applied to real data.

Introduction Current guidelines recommend adequate anticoagulation for at least 3 weeks pre‐ and 4 weeks post‐direct current cardioversion (DCCV) to reduce thrombo‐embolic risk in patients with atrial fibrillation (AF) lasting greater than 48 h. No specific recommendations exist for DCCV in patients that have undergone left atrial appendage occlusion (LAAO), many of whom are ineligible for anticoagulation. This study aims to observe the efficacy and safety of DCCV post‐LAAO in everyday clinical practice. Methods This prospective multicenter registry included DCCVs in patients post‐LAAO. Imaging strategy or anticoagulation treatment around DCCV were analyzed. Complications during 30‐day follow‐up were registered. DCCVs performed in accordance with current guidelines for the general AF population were compared to DCCVs performed deviating from these guidelines. Results In 93 patients (age 65 ± 17 years, CHA2DS2‐VASC 3.0 ± 1.3) 284 DCCVs were performed between 2010 and 2018, in 271 sinus rhythm was restored. A wide variety of imaging or anticoagulation strategies around DCCV was observed; in 128 episodes strategies deviated from current guidelines. No thrombo‐embolic events were observed after any DCCV during 30‐day follow‐up. In 34 DCCVs trans‐esophageal echocardiography (TOE) was performed before DCCV to exclude cardiac thrombi and/or (re‐)verify adequate device positioning. In two patients without post‐LAAO imaging before DCCV, a device rotation or embolization was observed during scheduled TOE after LAAO. Conclusion DCCV in AF patients after LAAO is highly effective. No thrombo‐embolic events were observed in any patient in this observational cohort, regardless of the periprocedural anticoagulation or imaging strategy. Confirmation of adequate device positioning at least once before DCCV seems recommendable.

SUMMARYFull waveform inversion suffers from local minima, due to a lack of low frequencies in the data. A reflector below the zone of interest may, however, help in recovering the long-wavelength components of a velocity perturbation, as demonstrated in a paper by Mora. With the Born approximation for the perturbation in a reference model consisting of two homogeneous isotropic acoustic halfspaces, analytic expressions can be found that describe the spatial spectrum of the recorded seismic signal as a function of the spatial spectrum of the inhomogeneity. We study this spectrum in more detail by separately considering direct, reflected and head waves. Taking the reflection coefficient of the deeper reflector into account, we obtain sensitivity estimates for each of these types of waves. Although the head waves have a relatively small contribution to the reconstruction of the velocity perturbation, compared to the other waves, they contain reliable long-wavelength information that can be beneficial for full waveform inversion.