Does the BICEP2 Observation of Cosmological Tensor Modes Imply an Era of Nearly Planckian Energy Densities?

BICEP2 observations, interpreted most simply, suggest an era of inflation with energy densities of order ($10^{16}\, {\rm GeV})^4$, not far below the Planck density. However, models of TeV gravity with large extra dimensions might allow a very different interpretation involving much more modest energy scales. We discuss the viability of inflation in such models, and conclude that existing scenarios do not provide attractive alternatives to single field inflation in four dimensions. Because the detection of tensor modes strengthens our confidence that inflation occurred, it disfavors models of large extra dimensions, at least for the moment.Comment: 4 pages, v3: version to appear in JHE

Determination of Nonlinear Genetic Architecture using Compressed Sensing

We introduce a statistical method that can reconstruct nonlinear genetic models (i.e., including epistasis, or gene-gene interactions) from phenotype-genotype (GWAS) data. The computational and data resource requirements are similar to those necessary for reconstruction of linear genetic models (or identification of gene-trait associations), assuming a condition of generalized sparsity, which limits the total number of gene-gene interactions. An example of a sparse nonlinear model is one in which a typical locus interacts with several or even many others, but only a small subset of all possible interactions exist. It seems plausible that most genetic architectures fall in this category. Our method uses a generalization of compressed sensing (L1-penalized regression) applied to nonlinear functions of the sensing matrix. We give theoretical arguments suggesting that the method is nearly optimal in performance, and demonstrate its effectiveness on broad classes of nonlinear genetic models using both real and simulated human genomes.Comment: 20 pages, 8 figures. arXiv admin note: text overlap with arXiv:1408.342

Instability of Quantum de Sitter Spacetime

Quantized fields (e.g., the graviton itself) in de Sitter (dS) spacetime lead to particle production: specifically, we consider a thermal spectrum resulting from the dS (horizon) temperature. The energy required to excite these particles reduces slightly the rate of expansion and eventually modifies the semiclassical spacetime geometry. The resulting manifold no longer has constant curvature nor time reversal invariance, and back-reaction renders the classical dS background unstable to perturbations. In the case of AdS, there exists a global static vacuum state; in this state there is no particle production and the analogous instability does not arise.Comment: 3 pages, v2: version to appear in JHE

Repeat prescribing of medications: a system-centred risk management model for primary care organisations

Rationale, aims and objectives: Reducing preventable harm from repeat medication prescriptions is a patient safety priority worldwide. In the United Kingdom, repeat prescriptions items issued has doubled in the last 20 years from 5.8 to 13.3 items per patient per annum. This has significant resource implications and consequences for avoidable patient harms. Consequently, we aimed to test a risk management model to identify, measure, and reduce repeat prescribing system risks in primary care. Methods: All 48 general medical practices in National Health Service (NHS) Lambeth Clinical Commissioning Group (an inner city area of south London in England) were recruited. Multiple interventions were implemented, including educational workshops, a web-based risk monitoring system, and external reviews of repeat prescribing system risks by clinicians. Data were collected via documentation reviews and interviews and subject to basic thematic and descriptive statistical analyses. Results: Across the 48 participating general practices, 62 unique repeat prescribing risks were identified on 505 occasions (eg, practices frequently experiencing difficulty interpreting medication changes on hospital discharge summaries), equating to a mean of 8.1 risks per practice (range: 1-33; SD = 7.13). Seven hundred sixty-seven system improvement actions were recommended across 96 categories (eg, alerting hospitals to illegible writing and delays with discharge summaries) with a mean of 15.6 actions per practice (range: 0-34; SD = 8.0). Conclusions: The risk management model tested uncovered important safety concerns and facilitated the development and communication of related improvement recommendations. System-wide information on hazardous repeat prescribing and how this could be mitigated is very limited. The approach reported may have potential to close this gap and improve the reliability of general practice systems and patient safety, which should be of high interest to primary care organisations internationally

New Active Asteroid 313P/Gibbs

We present initial observations of the newly-discovered active asteroid 313P/Gibbs (formerly P/2014 S4), taken to characterize its nucleus and comet-like activity. The central object has a radius $\sim$0.5 km (geometric albedo 0.05 assumed). We find no evidence for secondary nuclei and set (with qualifications) an upper limit to the radii of such objects near 25 m, assuming the same albedo. Both aperture photometry and a morphological analysis of the ejected dust show that mass-loss is continuous at rates $\sim$0.2 to 0.4 kg s$^{-1}$, inconsistent with an impact origin. Large dust particles, with radii $\sim$50 to 100 $\mu$m, dominate the optical appearance. At 2.4 AU from the Sun, the surface equilibrium temperatures are too low for thermal or desiccation stresses to be responsible for the ejection of dust. No gas is spectroscopically detected (limiting the gas mass loss rate to $<$1.8 kg s$^{-1}$). However, the protracted emission of dust seen in our data and the detection of another episode of dust release near perihelion, in archival observations from 2003, are highly suggestive of an origin by the sublimation of ice. Coincidentally, the orbit of 313P/Gibbs is similar to those of several active asteroids independently suspected to be ice sublimators, including P/2012 T1, 238P/Read and 133P/Elst-Pizarro, suggesting that ice is abundant in the outer asteroid belt.Comment: 24 pages, 7 figures, accepted The Astronomical Journa

Synthetic Peptides with Inadvertent Chemical Modifications Can Activate Potentially Autoreactive T Cells

The human CD8+ T cell clone 6C5 has previously been shown to recognize the tert-butyl-modified Bax161–170 peptide LLSY(3-tBu)FGTPT presented by HLA-A*02:01. This nonnatural epitope was likely created as a by-product of fluorenylmethoxycarbonyl protecting group peptide synthesis and bound poorly to HLA-A*02:01. In this study, we used a systematic approach to identify and characterize natural ligands for the 6C5 TCR. Functional analyses revealed that 6C5 T cells only recognized the LLSYFGTPT peptide when tBu was added to the tyrosine residue and did not recognize the LLSYFGTPT peptide modified with larger (di-tBu) or smaller chemical groups (Me). Combinatorial peptide library screening further showed that 6C5 T cells recognized a series of self-derived peptides with dissimilar amino acid sequences to LLSY(3-tBu)FGTPT. Structural studies of LLSY(3-tBu)FGTPT and two other activating nonamers (IIGWMWIPV and LLGWVFAQV) in complex with HLA-A*02:01 demonstrated similar overall peptide conformations and highlighted the importance of the position (P) 4 residue for T cell recognition, particularly the capacity of the bulky amino acid tryptophan to substitute for the tBu-modified tyrosine residue in conjunction with other changes at P5 and P6. Collectively, these results indicated that chemical modifications directly altered the immunogenicity of a synthetic peptide via molecular mimicry, leading to the inadvertent activation of a T cell clone with unexpected and potentially autoreactive specificities