Practical approach on frail older patients attended for acute heart failure

Acute heart failure (AHF) is a multi-organ dysfunction syndrome. In addition to known cardiac dysfunction, non-cardiac comorbidity, frailty and disability are independent risk factors of mortality, morbidity, cognitive and functional decline, and risk of institutionalization. Frailty, a treatable and potential reversible syndrome very common in older patients with AHF, increases the risk of disability and other adverse health outcomes. This position paper highlights the need to identify frailty in order to improve prognosis, the risk-benefits of invasive diagnostic and therapeutic procedures, and the definition of older-person-centered and integrated care plans

Atrial fibrillation impairs the diagnostic performance of cardiac natriuretic peptides in dyspneic patients. results from the BACH Study (Biomarkers in ACute Heart Failure)

Objectives: The purpose of this study was to assess the impact of atrial fibrillation (AF) on the performance of mid-region amino terminal pro-atrial natriuretic peptide (MR-proANP) in comparison with the B-type peptides (BNP and NT-proBNP) for diagnosis of acute heart failure (HF) in dyspneic patients. Background: The effects of AF on the diagnostic and prognostic performance of MR-proANP in comparison with the B type natriuretic peptides have not been previously reported. Methods: A total of 1,445 patients attending the emergency department with acute dyspnea had measurements taken of MR-proANP, BNP, and NT-proBNP values on enrollment to the BACH trial and were grouped according to presence or absence of AF and HF. Results: AF was present in 242 patients. Plasma concentrations of all three peptides were lowest in those with neither AF nor HF and AF without HF was associated with markedly increased levels (p < 0.00001). HF with or without AF was associated with a significant further increment (p < 0.00001 for all three markers). Areas under receiver operator characteristic curves (AUCs) for discrimination of acute HF were similar and powerful for all peptides without AF (0.893 to 0.912; all p < 0.001) with substantial and similar reductions (0.701 to 0.757) in the presence of AF. All 3 peptides were independently prognostic but there was no interaction between any peptide and AF for prediction of all-cause mortality. Conclusions: AF is associated with increased plasma natriuretic peptide (MR-proANP, BNP and NT-proBNP) levels in the absence of HF. The diagnostic performance of all three peptides is impaired by AF. This warrants consideration of adjusted peptide thresholds for diagnostic use in AF and mandates the continued search for markers free of confounding by AF

Two-neutron knockout from neutron-deficient 34^{34}Ar, 30^{30}S, and 26^{26}Si

Two-neutron knockout reactions from nuclei in the proximity of the proton dripline have been studied using intermediate-energy beams of neutron-deficient $^{34}$Ar, $^{30}$S, and $^{26}$Si. The inclusive cross sections, and also the partial cross sections for the population of individual bound final states of the $^{32}$Ar, $^{28}$S and $^{24}$Si knockout residues, have been determined using the combination of particle and $\gamma$-ray spectroscopy. Similar to the two-proton knockout mechanism on the neutron-rich side of the nuclear chart, these two-neutron removal reactions from already neutron-deficient nuclei are also shown to be consistent with a direct reaction mechanism.Comment: Phys. Rev. C, rapid communication, in pres

The condition-dependent transcriptional landscape of Burkholderia pseudomallei

This is the final version of the article. Available from the publisher via the DOI in this record.Burkholderia pseudomallei (Bp), the causative agent of the often-deadly infectious disease melioidosis, contains one of the largest prokaryotic genomes sequenced to date, at 7.2 Mb with two large circular chromosomes (1 and 2). To comprehensively delineate the Bp transcriptome, we integrated whole-genome tiling array expression data of Bp exposed to >80 diverse physical, chemical, and biological conditions. Our results provide direct experimental support for the strand-specific expression of 5,467 Sanger protein-coding genes, 1,041 operons, and 766 non-coding RNAs. A large proportion of these transcripts displayed condition-dependent expression, consistent with them playing functional roles. The two Bp chromosomes exhibited dramatically different transcriptional landscapes--Chr 1 genes were highly and constitutively expressed, while Chr 2 genes exhibited mosaic expression where distinct subsets were expressed in a strongly condition-dependent manner. We identified dozens of cis-regulatory motifs associated with specific condition-dependent expression programs, and used the condition compendium to elucidate key biological processes associated with two complex pathogen phenotypes--quorum sensing and in vivo infection. Our results demonstrate the utility of a Bp condition-compendium as a community resource for biological discovery. Moreover, the observation that significant portions of the Bp virulence machinery can be activated by specific in vitro cues provides insights into Bp's capacity as an "accidental pathogen", where genetic pathways used by the bacterium to survive in environmental niches may have also facilitated its ability to colonize human hosts.This work was funded by a core grant provided by the Agency for Science, Technology and Research to the Genome Institute of Singapore, and funding from the Defence Medical and Environmental Research Institute, Singapore. This work was supported in part through NIAID contract HHSN266200400035C to BWS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Characterisation of a small electrode HPGe detector

© 2019 Elsevier B.V. Small electrode HPGe detectors in an inverted coaxial geometry are increasingly in use in applications where both high efficiency and excellent energy resolution are required. The unusual electric field configuration of these detectors results in extremely long charge collection times compared to planar and coaxial devices. In this work we have characterised such a detector using gamma-ray coincidence measurements and optimised an electric field simulation to reproduce the positional variation of detector response. We show that, alongside accurate crystal geometry and applied electric potential, a temperature correction is crucial to correctly determining appropriate charge carrier mobility parameters. This work will help to guide the future development of HPGE detectors for applications including radioactive waste assay, radio-isotope dating, and fundamental nuclear physics

Intraflagellar Transport (IFT) Protein IFT25 Is a Phosphoprotein Component of IFT Complex B and Physically Interacts with IFT27 in Chlamydomonas

BACKGROUND: Intraflagellar transport (IFT) is the bidirectional movement of IFT particles between the cell body and the distal tip of a flagellum. Organized into complexes A and B, IFT particles are composed of at least 18 proteins. The function of IFT proteins in flagellar assembly has been extensively investigated. However, much less is known about the molecular mechanism of how IFT is regulated. METHODOLOGY/PRINCIPAL FINDINGS: We herein report the identification of a novel IFT particle protein, IFT25, in Chlamydomonas. Dephosphorylation assay revealed that IFT25 is a phosphoprotein. Biochemical analysis of temperature sensitive IFT mutants indicated that IFT25 is an IFT complex B subunit. In vitro binding assay confirmed that IFT25 binds to IFT27, a Rab-like small GTPase component of the IFT complex B. Immunofluorescence staining showed that IFT25 has a punctuate flagellar distribution as expected for an IFT protein, but displays a unique distribution pattern at the flagellar base. IFT25 co-localizes with IFT27 at the distal-most portion of basal bodies, probably the transition zones, and concentrates in the basal body region by partially overlapping with other IFT complex B subunits, such as IFT46. Sucrose density gradient centrifugation analysis demonstrated that, in flagella, the majority of IFT27 and IFT25 including both phosphorylated and non-phosphorylated forms are cosedimented with other complex B subunits in the 16S fractions. In contrast, in cell body, only a fraction of IFT25 and IFT27 is integrated into the preassembled complex B, and IFT25 detected in complex B is preferentially phosphorylated. CONCLUSION/SIGNIFICANCE: IFT25 is a phosphoprotein component of IFT particle complex B. IFT25 directly interacts with IFT27, and these two proteins likely form a subcomplex in vivo. We postulate that the association and disassociation between the subcomplex of IFT25 and IFT27 and complex B might be involved in the regulation of IFT

The EIF4EBP3 translational repressor is a marker of CDC73 tumor suppressor haploinsufficiency in a parathyroid cancer syndrome

Germline mutation of the tumor suppressor gene CDC73 confers susceptibility to the hyperparathyroidism-jaw tumor syndrome associated with a high risk of parathyroid malignancy. Inactivating CDC73 mutations have also been implicated in sporadic parathyroid cancer, but are rare in sporadic benign parathyroid tumors. The molecular pathways that distinguish malignant from benign parathyroid transformation remain elusive. We previously showed that a hypomorphic allele of hyrax (hyx), the Drosophila homolog of CDC73, rescues the loss-of-ventral-eye phenotype of lobe, encoding the fly homolog of Akt1s1/ PRAS40. We report now an interaction between hyx and Tor, a central regulator of cell growth and autophagy, and show that eukaryotic translation initiation factor 4E-binding protein (EIF4EBP), a translational repressor and effector of mammalian target of rapamycin (mTOR), is a conserved target of hyx/CDC73. Flies heterozygous for Tor and hyx, but not Mnn1, the homolog of the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor associated with benign parathyroid tumors, are starvation resistant with reduced basal levels of Thor/4E-BP. Human peripheral blood cell levels of EIF4EBP3 were reduced in patients with CDC73, but not MEN1, heterozygosity. Chromatin immunoprecipitation demonstrated occupancy of EIF4EBP3 by endogenous parafibromin. These results show that EIF4EBP3 is a peripheral marker of CDC73 function distinct from MEN1-regulated pathways, and suggest a model whereby starvation resistance and/or translational de-repression contributes to parathyroid malignant transformation

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives