QRS complex and T wave planarity for the efficacy prediction of automatic implantable defibrillators.

OBJECTIVE To test the hypothesis that in recipients of primary prophylactic implantable cardioverter-defibrillators (ICDs), the non-planarity of ECG vector loops predicts (a) deaths despite ICD protection and (b) appropriate ICD shocks. METHODS Digital pre-implant ECGs were collected in 1948 ICD recipients: 21.4% females, median age 65 years, 61.5% ischaemic heart disease (IHD). QRS and T wave three-dimensional loops were constructed using singular value decomposition that allowed to measure the vector loop planarity. The non-planarity, that is, the twist of the three-dimensional loops out of a single plane, was related to all-cause mortality (n=294; 15.3% females; 68.7% IHD) and appropriate ICD shocks (n=162; 10.5% females; 87.7% IHD) during 5-year follow-up after device implantation. Using multivariable Cox regression, the predictive power of QRS and T wave non-planarity was compared with that of age, heart rate, left ventricular ejection fraction, QRS duration, spatial QRS-T angle, QTc interval and T-peak to T-end interval. RESULTS QRS non-planarity was significantly (p<0.001) associated with follow-up deaths despite ICD protection with HR of 1.339 (95% CI 1.165 to 1.540) but was only univariably associated with appropriate ICD shocks. Non-planarity of the T wave loop was the only ECG-derived index significantly (p<0.001) associated with appropriate ICD shocks with multivariable Cox regression HR of 1.364 (1.180 to 1.576) but was not associated with follow-up mortality. CONCLUSIONS The analysed data suggest that QRS and T wave non-planarity might offer distinction between patients who are at greater risk of death despite ICD protection and those who are likely to use the defibrillator protection

QRS micro-fragmentation as a mortality predictor.

AIMS Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-μf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-μf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-μf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-μf prospectively at 3.5%. When QRS-μf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION In three populations with different clinical characteristics, QRS-μf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-μf values are likely responsible for the predictive power of visible QRS-Mf. KEY QUESTION KEY FINDING TAKE-HOME MESSAGE QRS-μf is a strong predictor of worsened survival. It can be assessed in standard short-term 12-lead electrocardiograms

The effect of Germany’s federalism on student success : The “Index of Commitment“ as comparative measure for study and examination regulations

Long-term studies and drop-outs are a major issue in higher education research, but explanatory factors have often been focusing on attitudinal and sociological characteristics using student surveys as methodology. Institutional rules regarding study and learning regulations have often been neglected, although recent research has shown that they incentivize student behaviour. We develop and Index of Commitment (IOC) to cover these rules over different types of study phases and different types of commitments of different actors. We distinguish between an early study phase, a main phase and a late study phase and commitments regarding consultation and examination rules by the state, a higher education institution (HEI) and students. This paper shows empirically that there is a considerable variance of these rules between the 16 German states, which are responsible for the legislation and financing of most of the higher education institutions in Germany. We find states with very soft regulation, where legislation sets almost no rules and student autonomy is held in high regard and states with very precise rules setting strong incentives and leaving only little room for implementation to the HEI. We can show that our index correlates with the percentage of students successfully finishing their degree in time in a state. By presenting our index, we provide a comprehensive understanding of the commitment of study and examination regulations. The findings and insights can contribute to the ongoing discourse on student autonomy and state control in higher education, as well as inform policy makers and educational institutions in developing effective strategies to address dropout and long-term study. It also shows again that “bringing the state back in” in higher education research is important

Surface state engineering of molecule-molecule interactions

Engineering the electronic structure of organics through interface manipulation, particularly the interface dipole and the barriers to charge carrier injection, is of essential importance to improved organic devices. This requires the meticulous fabrication of desired organic structures by precisely controlling the interactions between molecules. The well-known principles of organic coordination chemistry cannot be applied without proper consideration of extra molecular hybridization, charge transer and dipole formation at the interfaces. Here we identify the interplay between energy level alignment, charge transfer, surface dipole and charge pillow effect and show how these effects collectively determine the net force between adsorbed porphyrin 2H-TPP on Cu(111). We show that the forces between supported porphyrins can be altered by controlling the amount of charge transferred across the interface accurately through the relative alignment of molecular electronic levels with respect to the Shockley surface state of the metal substrate, and hence govern the self-assembly of the molecules

Secondary Chromosomal Attachment Site and Tandem Integration of the Mobilizable Salmonella Genomic Island 1

The Salmonella genomic island 1 is an integrative mobilizable element (IME) originally identified in epidemic multidrug-resistant Salmonella enterica serovar Typhimurium (S. Typhimurium) DT104. SGI1 contains a complex integron, which confers various multidrug resistance phenotypes due to its genetic plasticity. Previous studies have shown that SGI1 integrates site-specifically into the S. enterica, Escherichia coli, or Proteus mirabilis chromosome at the 3′ end of thdF gene (attB site)

The ALMA Spectroscopic Survey in the HUDF: CO Luminosity Functions and the Molecular Gas Content of Galaxies through Cosmic History

We use the results from the ALMA large program ASPECS, the spectroscopic survey in the Hubble Ultra Deep Field (HUDF), to constrain CO luminosity functions of galaxies and the resulting redshift evolution of ρ(H2). The broad frequency range covered enables us to identify CO emission lines of different rotational transitions in the HUDF at z > 1. We find strong evidence that the CO luminosity function evolves with redshift, with the knee of the CO luminosity function decreasing in luminosity by an order of magnitude from ~2 to the local universe. Based on Schechter fits, we estimate that our observations recover the majority (up to ~90%, depending on the assumptions on the faint end) of the total cosmic CO luminosity at z = 1.0–3.1. After correcting for CO excitation, and adopting a Galactic CO-to-H2 conversion factor, we constrain the evolution of the cosmic molecular gas density ρ(H2): this cosmic gas density peaks at z ~ 1.5 and drops by a factor of ${6.5}_{-1.4}^{+1.8}$ to the value measured locally. The observed evolution in ρ(H2), therefore, closely matches the evolution of the cosmic star formation rate density ρ SFR. We verify the robustness of our result with respect to assumptions on source inclusion and/or CO excitation. As the cosmic star formation history can be expressed as the product of the star formation efficiency and the cosmic density of molecular gas, the similar evolution of ρ(H2) and ρ SFR leaves only little room for a significant evolution of the average star formation efficiency in galaxies since z ~ 3 (85% of cosmic history)

Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections

The increasing incidence of aciclovir- (ACV) resistant strains in patients with ocular herpes simplex virus (HSV) infections is a major health problem in industrialized countries. In the present study, the humanized monoclonal antibody (mAb) hu2c targeting the HSV-1/2 glycoprotein B was examined for its efficacy towards ACV-resistant infections of the eye in the mouse model of acute retinal necrosis (ARN). BALB/c mice were infected by microinjection of an ACV-resistant clinical isolate into the anterior eye chamber to induce ARN and systemically treated with mAb hu2c at 24 h prior (pre-e

Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study

Purpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopatho-logic variables with survival was evaluated in a large multi-institutional European cohort. Experimental Design: Data from 185 patients were retrospec-tively collected in 23 European GIST reference centers. Propen-sity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Uni-variate and multivariate unweighted and weighted Cox propor-tional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival. Results: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79- 2.28]. The variables consistently associated with worse survival out-comes were high mitotic index and nongastric tumor location. Conclusions: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.Peer reviewe

The Evolution of the Baryons Associated with Galaxies Averaged over Cosmic Time and Space

We combine the recent determination of the evolution of the cosmic density of molecular gas (H2) using deep, volumetric surveys, with previous estimates of the cosmic density of stellar mass, star formation rate and atomic gas (H i), to constrain the evolution of baryons associated with galaxies averaged over cosmic time and space. The cosmic H i and H2 densities are roughly equal at z ~ 1.5. The H2 density then decreases by a factor ${6}_{-2}^{+3}$ to today's value, whereas the H i density stays approximately constant. The stellar mass density is increasing continuously with time and surpasses that of the total gas density (H i and H2) at redshift z ~ 1.5. The growth in stellar mass cannot be accounted for by the decrease in cosmic H2 density, necessitating significant accretion of additional gas onto galaxies. With the new H2 constraints, we postulate and put observational constraints on a two-step gas accretion process: (i) a net infall of ionized gas from the intergalactic/circumgalactic medium to refuel the extended H i reservoirs, and (ii) a net inflow of H i and subsequent conversion to H2 in the galaxy centers. Both the infall and inflow rate densities have decreased by almost an order of magnitude since z ~ 2. Assuming that the current trends continue, the cosmic molecular gas density will further decrease by about a factor of two over the next 5 Gyr, the stellar mass will increase by approximately 10%, and cosmic star formation activity will decline steadily toward zero, as the gas infall and accretion shut down