Systolic blood pressure reduction during the first 24 h in acute heart failure admission: friend or foe?

Aims: Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes. Methods and results: We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00–1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24 h for 180-day all-cause mortality was 1.01 (95% CI 1.00–1.03; P = 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h. Conclusions: In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients

Predictors and associations with outcomes of length of hospital stay in patients with acute heart failure: results from VERITAS

Background: The length of hospital stay (LOS) is important in patients admitted for acute heart failure (AHF) because it prolongs an unpleasant experience for the patients and adds substantially to health care costs. Methods and Results: We examined the association between LOS and baseline characteristics, 10-day post-discharge HF readmission, and 90-day post-discharge mortality in 1347 patients with AHF enrolled in the VERITAS program. Longer LOS was associated with greater HF severity and disease burden at baseline; however, most of the variability of LOS could not be explained by these factors. LOS was associated with a higher HF risk of both HF readmission (odds ratio for 1-day increase: 1.08; 95% confidence interval [CI] 1.01–1.16; P = .019) and 90-day mortality (hazard ratio for 1-day increase: 1.05; 95% CI 1.02–1.07; P < .001), although these associations are partially explained by concurrent end-organ damage and worsening heart failure during the first days of admission. Conclusions: In patients who have been admitted for AHF, longer length of hospital stay is associated with a higher rate of short-term mortality. Clinical Trial Registration: VERITAS-1 and -2: Clinicaltrials.gov identifiers NCT00525707 and NCT00524433

Probing semiclassical analogue gravity in Bose--Einstein condensates with widely tunable interactions

Bose-Einstein condensates (BEC) have recently been the subject of considerable study as possible analogue models of general relativity. In particular it was shown that the propagation of phase perturbations in a BEC can, under certain conditions, closely mimic the dynamics of scalar quantum fields in curved spacetimes. In two previous articles [gr-qc/0110036, gr-qc/0305061] we noted that a varying scattering length in the BEC corresponds to a varying speed of light in the ``effective metric''. Recent experiments have indeed achieved a controlled tuning of the scattering length in Rubidium 85. In this article we shall discuss the prospects for the use of this particular experimental effect to test some of the predictions of semiclassical quantum gravity, for instance, particle production in an expanding universe. We stress that these effects are generally much larger than the Hawking radiation expected from causal horizons, and so there are much better chances for their detection in the near future.Comment: 18 pages; uses revtex4. V2: Added brief discussion of "Bose-Nova" phenomenon, and appropriate reference

The Covariant Entropy Bound, Brane Cosmology, and the Null Energy Condition

In discussions of Bousso's Covariant Entropy Bound, the Null Energy Condition is always assumed, as a sufficient {\em but not necessary} condition which helps to ensure that the entropy on any lightsheet shall necessarily be finite. The spectacular failure of the Strong Energy Condition in cosmology has, however, led many astrophysicists and cosmologists to consider models of dark energy which violate {\em all} of the energy conditions, and indeed the current data do not completely rule out such models. The NEC also has a questionable status in brane cosmology: it is probably necessary to violate the NEC in the bulk in order to obtain a "self-tuning" theory of the cosmological constant. In order to investigate these proposals, we modify the Karch-Randall model by introducing NEC-violating matter into $AdS_5$ in such a way that the brane cosmological constant relaxes to zero. The entropy on lightsheets remains finite. However, we still find that the spacetime is fundamentally incompatible with the Covariant Entropy Bound machinery, in the sense that it fails the Bousso-Randall consistency condition. We argue that holography probably forbids all {\em cosmological} violations of the NEC, and that holography is in fact the fundamental physical principle underlying the cosmological version of the NEC.Comment: 21 pages, 3 figures, version 2:corrected and greatly improved discussion of the Bousso-Randall consistency check, references added; version3: more references added, JHEP versio

Neuroplastin genetically interacts with Cadherin 23 and the encoded isoform Np55 is sufficient for cochlear hair cell function and hearing

Mammalian hearing involves the mechanoelectrical transduction (MET) of sound-induced fluid waves in the cochlea. Essential to this process are the specialised sensory cochlear cells, the inner (IHCs) and outer hair cells (OHCs). While genetic hearing loss is highly heterogeneous, understanding the requirement of each gene will lead to a better understanding of the molecular basis of hearing and also to therapeutic opportunities for deafness. The Neuroplastin (Nptn) gene, which encodes two protein isoforms Np55 and Np65, is required for hearing, and homozygous loss-of-function mutations that affect both isoforms lead to profound deafness in mice. Here we have utilised several distinct mouse models to elaborate upon the spatial, temporal, and functional requirement of Nptn for hearing. While we demonstrate that both Np55 and Np65 are present in cochlear cells, characterisation of a Np65-specific mouse knockout shows normal hearing thresholds indicating that Np65 is functionally redundant for hearing. In contrast, we find that Nptn-knockout mice have significantly reduced maximal MET currents and MET channel open probabilities in mature OHCs, with both OHCs and IHCs also failing to develop fully mature basolateral currents. Furthermore, comparing the hearing thresholds and IHC synapse structure of Nptn-knockout mice with those of mice that lack Nptn only in IHCs and OHCs shows that the majority of the auditory deficit is explained by hair cell dysfunction, with abnormal afferent synapses contributing only a small proportion of the hearing loss. Finally, we show that continued expression of Neuroplastin in OHCs of adult mice is required for membrane localisation of Plasma Membrane Ca2+ ATPase 2 (PMCA2), which is essential for hearing function. Moreover, Nptn haploinsufficiency phenocopies Atp2b2 (encodes PMCA2) mutations, with heterozygous Nptn-knockout mice exhibiting hearing loss through genetic interaction with the Cdh23ahl allele. Together, our findings provide further insight to the functional requirement of Neuroplastin for mammalian hearing

Non-minimal coupling of the scalar field and inflation

We study the prescriptions for the coupling constant of a scalar field to the Ricci curvature of spacetime in specific gravity and scalar field theories. The results are applied to the most popular inflationary scenarios of the universe; their theoretical consistency and certain observational constraints are discussed.Comment: 23 pages, LaTex, no figures, to appear in Physical Review

Classical inflaton field induced creation of superheavy dark matter

We calculate analytically and numerically the production of superheavy dark matter (X) when it is coupled to the inflaton field \phi within the context of a slow-roll m_\phi^2 \phi^2/2 inflationary model with coupling g^2 X^2 \phi^2/2. We find that X particles with a mass as large as 1000 H_i, where H_i is the value of the Hubble expansion rate at the end of inflation, can be produced in sufficient abundance to be cosmologically significant today. This means that superheavy dark matter may have a mass of up to 10^{-3} Planck mass. We also derive a simple formula that can be used to estimate particle production as a result of a quantum field's interaction with a general class of homogeneous classical fields. Finally, we note that the combined effect of the inflaton field and the gravitational field on the X field causes the production to be a nonmonotonic function of g^2.Comment: 42 page LaTeX file with 8 PostScript figures included with eps

Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation

The current status of electric dipole moments of diamagnetic atoms which involves the synergy between atomic experiments and three different theoretical areas -- particle, nuclear and atomic is reviewed. Various models of particle physics that predict CP violation, which is necessary for the existence of such electric dipole moments, are presented. These include the standard model of particle physics and various extensions of it. Effective hadron level combined charge conjugation (C) and parity (P) symmetry violating interactions are derived taking into consideration different ways in which a nucleon interacts with other nucleons as well as with electrons. Nuclear structure calculations of the CP-odd nuclear Schiff moment are discussed using the shell model and other theoretical approaches. Results of the calculations of atomic electric dipole moments due to the interaction of the nuclear Schiff moment with the electrons and the P and time-reversal (T) symmetry violating tensor-pseudotensor electron-nucleus are elucidated using different relativistic many-body theories. The principles of the measurement of the electric dipole moments of diamagnetic atoms are outlined. Upper limits for the nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained combining the results of atomic experiments and relativistic many-body theories. The coefficients for the different sources of CP violation have been estimated at the elementary particle level for all the diamagnetic atoms of current experimental interest and their implications for physics beyond the standard model is discussed. Possible improvements of the current results of the measurements as well as quantum chromodynamics, nuclear and atomic calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for EPJ

Before and After: Comparison of Legacy and Harmonized TCGA Genomic Data Commons’ Data

We present a systematic analysis of the effects of synchronizing a large-scale, deeply characterized, multi-omic dataset to the current human reference genome, using updated software, pipelines, and annotations. For each of 5 molecular data platforms in The Cancer Genome Atlas (TCGA)—mRNA and miRNA expression, single nucleotide variants, DNA methylation and copy number alterations—comprehensive sample, gene, and probe-level studies were performed, towards quantifying the degree of similarity between the ‘legacy’ GRCh37 (hg19) TCGA data and its GRCh38 (hg38) version as ‘harmonized’ by the Genomic Data Commons. We offer gene lists to elucidate differences that remained after controlling for confounders, and strategies to mitigate their impact on biological interpretation. Our results demonstrate that the hg19 and hg38 TCGA datasets are very highly concordant, promote informed use of either legacy or harmonized omics data, and provide a rubric that encourages similar comparisons as new data emerge and reference data evolve. Gao et al. performed a systematic analysis of the effects of synchronizing the large-scale, widely used, multi-omic dataset of The Cancer Genome Atlas to the current human reference genome. For each of the five molecular data platforms assessed, they demonstrated a very high concordance between the ‘legacy’ GRCh37 (hg19) TCGA data and its GRCh38 (hg38) version as ‘harmonized’ by the Genomic Data Commons

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types