Local non-Gaussianity from rapidly varying sound speeds

We study the effect of non-trivial sound speeds on local-type non-Gaussianity during multiple-field inflation. To this end, we consider a model of multiple-field DBI and use the deltaN formalism to track the super-horizon evolution of perturbations. By adopting a sum separable Hubble parameter we derive analytic expressions for the relevant quantities in the two-field case, valid beyond slow variation. We find that non-trivial sound speeds can, in principle, curve the trajectory in such a way that significant local-type non-Gaussianity is produced. Deviations from slow variation, such as rapidly varying sound speeds, enhance this effect. To illustrate our results we consider two-field inflation in the tip regions of two warped throats and find large local-type non-Gaussianity produced towards the end of the inflationary process.Comment: 30 pages, 7 figures; typos corrected, references added, accepted for publication in JCA

A geometric description of the non-Gaussianity generated at the end of multi-field inflation

In this paper we mainly focus on the curvature perturbation generated at the end of multi-field inflation, such as the multi-brid inflation. Since the curvature perturbation is produced on the super-horizon scale, the bispectrum and trispectrum have a local shape. The size of bispectrum is measured by $f_{NL}$ and the trispectrum is characterized by two parameters $\tau_{NL}$ and $g_{NL}$. For simplicity, the trajectory of inflaton is assumed to be a straight line in the field space and then the entropic perturbations do not contribute to the curvature perturbation during inflation. As long as the background inflaton path is not orthogonal to the hyper-surface for inflation to end, the entropic perturbation can make a contribution to the curvature perturbation at the end of inflation and a large local-type non-Gaussiantiy is expected. An interesting thing is that the non-Gaussianity parameters are completely determined by the geometric properties of the hyper-surface of the end of inflation. For example, $f_{NL}$ is proportional to the curvature of the curve on this hyper-surface along the adiabatic direction and $g_{NL}$ is related to the change of the curvature radius per unit arc-length of this curve. Both $f_{NL}$ and $g_{NL}$ can be positive or negative respectively, but $\tau_{NL}$ must be positive and not less than $({6\over 5}f_{NL})^2$.Comment: 19 pages, 4 figures; refs added; a correction to \tau_{NL} for n-field inflation added, version accepted for publication in JCA

Loop Corrections to Cosmological Perturbations in Multi-field Inflationary Models

We investigate one-loop quantum corrections to the power spectrum of adiabatic perturbation from entropy modes/adiabatic mode cross-interactions in multiple DBI inflationary models. We find that due to the non-canonical kinetic term in DBI models, the loop corrections are enhanced by slow-varying parameter $\epsilon$ and small sound speed $c_s$. Thus, in general the loop-corrections in multi-DBI models can be large. Moreover, we find that the loop-corrections from adiabatic/entropy cross-interaction vertices are IR finite.Comment: 21 pages, 7 figures; v2, typos corrected, ref added; v3 typos corrected, version for publishing in jca

On primordial trispectrum from exchanging scalar modes in general multiple field inflationary models

We make an complementary investigation of the primordial trispectrum from exchanging intermediate scalar modes in multi-field inflation models with generalized kinetic terms. Together with the calculation of irreducible contributions to the primordial trispectrum in Ref.[103], we give the full leading-order primordial trispectrum in generalized multi-field models.Comment: 15 pages, 1 figure; v2 references adde

Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein

To discover novel genes underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry-matched controls. We observed a significant excess of rare protein-truncating variants among ALS cases, and these variants were concentrated in constrained genes. Through gene level analyses, we replicated known ALS genes including SOD1, NEK1 and FUS. We also observed multiple distinct protein-truncating variants in a highly constrained gene, DNAJC7. The signal in DNAJC7 exceeded genome-wide significance, and immunoblotting assays showed depletion of DNAJC7 protein in fibroblasts in a patient with ALS carrying the p.Arg156Ter variant. DNAJC7 encodes a member of the heat-shock protein family, HSP40, which, along with HSP70 proteins, facilitates protein homeostasis, including folding of newly synthesized polypeptides and clearance of degraded proteins. When these processes are not regulated, misfolding and accumulation of aberrant proteins can occur and lead to protein aggregation, which is a pathological hallmark of neurodegeneration. Our results highlight DNAJC7 as a novel gene for ALS

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Influence of discharge regime on the movement and refuge use of a freshwater fish in a drying temperate region

Understanding how the movement and habitat use of fishes are influenced by flow regimes is important in sustainably managing river ecosystems, particularly in regions undergoing drying due to climate change. Here, we aimed to determine how the movement of a freshwater fish from refuge pools is influenced by discharge and environmental variables in south‐western Australia, a region that has suffered an ~50% reduction in surface flows since the 1970s. We quantified the movement patterns of the freshwater plotosid Tandanus bostocki using acoustic telemetry in two rivers that had different flow regimes and habitat characteristics. We hypothesized that its movements would be positively influenced by discharge and it would also display a high degree of site fidelity. Fifty fish were tagged and monitored across both rivers for a 1‐year period. There was an overall significant positive relationship between daily movements from the monitored refuge pools with both discharge and solar irradiation in both rivers. However, there was a greater probability of movement at a lower magnitude of discharge in the regulated Harvey River, which was attributed to the influence of river gradient and prevalence of instream barriers moderating the effect of flow on movements in the Brunswick River. The species demonstrated a considerable degree of site fidelity and also displayed homing behaviour. The study suggests that the maintenance of key refuge pools during baseflow, and ensuring river connectivity during the key movement periods, would help maintain the viability of the species as river discharge continues to decline due to climate change