A Critical Appraisal of Short-Term End Points in Acute Heart Failure Clinical Trials

The prevalence of heart failure continues to grow, and this is accompanied by an increase in hospitalization for acute heart failure. Hospitalization for heart failure results in a trajectory shift of the syndrome and is associated with worsening outcomes, increased mortality risk, and high costs. Numerous clinical trials over the past 2 decades have had limited success, with no single agent shown to improve mortality risk. The lack of success is multifactorial and in part related to inadequate targets and end points selected for intervention, underscoring the need to better understand and define the pathophysiology of acute heart failure. To better inform future drug development, this review critically explores the short-term end points and outcomes that previous phase III acute heart failure trials have examined.     

Localization Properties of a Quasiperiodic Ladder under Physical Gain and Loss: Tuning of Critical Points,Mixed-Phase Zone and Mobility Edge

We explore the localization properties of a double-stranded ladder within a tight-binding framework where the site energies of different lattice sites are distributed in the cosine form following the Aubry–André–Harper (AAH) model. An imaginary site energy, which can be positive or negative, referred to as physical gain or loss, is included in each of these lattice sites which makes the system a non-Hermitian (NH) one. Depending on the distribution of imaginary site energies, we obtain balanced and imbalanced NH ladders of different types, and for all these cases, we critically investigate localization phenomena. Each ladder can be decoupled into two effective one-dimensional (1D) chains which exhibit two distinct critical points of transition from metallic to insulating (MI) phase. Because of the existence of two distinct critical points, a mixed-phase (MP) zone emerges which yields the possibility of getting a mobility edge (ME). The conducting behaviors of different energy eigenstates are investigated in terms of inverse participation ratio (IPR). The critical points and thus the MP window can be selectively controlled by tuning the strength of the imaginary site energies which brings a new insight into the localization aspect. A brief discussion on phase transition considering a multi-stranded ladder was also given as a general case, to make the present communication a self-contained one. Our theoretical analysis can be utilized to investigate the localization phenomena in different kinds of simple and complex quasicrystals in the presence of physical gain and/or loss.     

Toward a Critical Gerontology:

No abstract available for this article.     

The Amplification of Ribosomal RNA Genes Involves a Rolling Circle Intermediate

During the development of Xenopus oocytes there is a special DNA synthesis that leads to a thousandfold amplification of the genes that code for ribosomal RNA. We have used the electron microscope to study this process. Our primary observation is the presence of ribosomal DNA in rolling-circle intermediates at the time of amplification. We believe that these intermediates are involved in the amplification process, and as such offer the first example of the involvement of a rolling circle in the replication of eukaryotic DNA.     

Shiftless,a Critical Piece of the Innate Immune Response to Viral Infection

Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell.     

Points to consider when choosing a biopsy method in cases of pleurisy of unknown origin

Blind pleural needle biopsy and diagnostic thoracoscopy are procedures sometimes used in the work-up of a patient with pleural effusion of unknown origin. We reviewed 203 diagnostic thoracoscopies in patients with malignant pleural effusion to show the different location of pleural metastasis, some out of the reach of blind needle biopsy. Based on these data, we find diagnostic thoracoscopy a superior procedure because of its higher reliability, faster diagnostic results, slight or no complications, and the possibility of carrying out pleurodesis in the same examination.