The Neural Basis of Predicting the Outcomes of Imagined Actions

A key feature of human intelligence is the ability to predict the outcomes of one’s own actions prior to executing them. Action values are thought to be represented in part in the dorsal and ventral medial prefrontal cortex (mPFC), yet current studies have focused on the value of executed actions rather than the anticipated value of a planned action. Thus, little is known about the neural basis of how individuals think (or fail to think) about their actions and the potential consequences before they act. We scanned individuals with fMRI while they thought about performing actions that they knew would likely be rewarded or unrewarded. Here we show that merely imagining an unrewarded action, as opposed to imagining a rewarded action, increases activity in the dorsal anterior cingulate cortex, independently of subsequent actions. This activity overlaps with regions that respond to actual unrewarded actions. The findings show a distinct network that signals the prospective outcomes of one’s possible actions. A number of clinical disorders such as schizophrenia and drug abuse involve a failure to take the potential consequences of an action into account prior to acting. Our results thus suggest how dysfunctions of the mPFC may contribute to such failures

The prevalences of Salmonella Genomic Island 1 variants in human and animal Salmonella Typhimurium DT104 are distinguishable using a Bayesian approach

Throughout the 1990s, there was an epidemic of multidrug resistant Salmonella Typhimurium DT104 in both animals and humans in Scotland. The use of antimicrobials in agriculture is often cited as a major source of antimicrobial resistance in pathogenic bacteria of humans, suggesting that DT104 in animals and humans should demonstrate similar prevalences of resistance determinants. Until very recently, only the application of molecular methods would allow such a comparison and our understanding has been hindered by the fact that surveillance data are primarily phenotypic in nature. Here, using large scale surveillance datasets and a novel Bayesian approach, we infer and compare the prevalence of Salmonella Genomic Island 1 (SGI1), SGI1 variants, and resistance determinants independent of SGI1 in animal and human DT104 isolates from such phenotypic data. We demonstrate differences in the prevalences of SGI1, SGI1-B, SGI1-C, absence of SGI1, and tetracycline resistance determinants independent of SGI1 between these human and animal populations, a finding that challenges established tenets that DT104 in domestic animals and humans are from the same well-mixed microbial population

A Machine Learning Compatible Method For ordinal Propensity Score Stratification and Matching

Although machine learning techniques that estimate propensity scores for observational studies with multivalued treatments have advanced rapidly in recent years, the development of propensity score adjustment techniques has not kept pace. While machine learning propensity models provide numerous benefits, they do not produce a single variable balancing score that can be used for propensity score stratification and matching. This issue motivates the development of a flexible ordinal propensity scoring methodology that does not require parametric assumptions for the propensity model. The proposed method fits a one-parameter power function to the cumulative distribution function (CDF) of the generalized propensity score (GPS) vector resulting from any machine learning propensity model, and is henceforth called the GPS-CDF method. The estimated parameter from the GPS-CDF method

Clinical Severity of Clostridium difficile PCR Ribotype 027: A Case-Case Study

BACKGROUND: Clostridium difficile is a leading infectious cause of health care associated diarrhoea. Several industrialised countries have reported increased C. difficile infections and outbreaks, which have been attributed to the emergent PCR ribotype 027 strain. METHODS AND FINDINGS: We conducted a case-case study to compare severity of C. difficile disease for patients with 027 versus non-027 ribotypes. We retrospectively collected clinical information about 123/136 patients with C. difficile infections admitted to hospitals in the East of England region in 2006 and from whom stool isolates were cultured and ribotyped as part of an earlier national survey. We defined severe C. difficile disease as having one or more of shock, paralytic ileus, pseudo membranous colitis or toxic megacolon. Patient median age was 83 years old (range 3 to 98, interquartile range 75 to 89), 86% were prescribed antibiotics in the eight weeks before illness onset, 41% had ribotype 027 and 30-day all cause mortality during hospital admission was 21%. Severe disease occurred in 24% (95%CI 13% to 37%) and 17% (95%CI 9% to 27%) of patients with PCR ribotype 027 and non-027 ribotypes respectively. In a multivariable model, ribotype 027 was not associated with severe disease after adjusting for sex, discharge from hospital prior to 60 days of current admission, gastroenteritis on admission, number of initiator antibiotics for C. difficile disease, and hospital where the patient was admitted. CONCLUSIONS: Our study found no evidence to support previous assertions that ribotype 027 is more virulent than other PCR ribotypes. This finding raises questions about the contribution of this strain to the recent increase in C. difficile disease throughout North America and Europe

Incident disease associations with mosaic chromosomal alterations on autosomes, X and Y chromosomes: insights from a phenome-wide association study in the UK Biobank.

BackgroundMosaic chromosomal alterations (mCAs) are large chromosomal gains, losses and copy-neutral losses of heterozygosity (LOH) in peripheral leukocytes. While many individuals with detectable mCAs have no notable adverse outcomes, mCA-associated gene dosage alterations as well as clonal expansion of mutated leukocyte clones could increase susceptibility to disease.ResultsWe performed a phenome-wide association study (PheWAS) using existing data from 482,396 UK Biobank (UKBB) participants to investigate potential associations between mCAs and incident disease. Of the 1290 ICD codes we examined, our adjusted analysis identified a total of 50 incident disease outcomes associated with mCAs at PheWAS significance levels. We observed striking differences in the diseases associated with each type of alteration, with autosomal mCAs most associated with increased hematologic malignancies, incident infections and possibly cancer therapy-related conditions. Alterations of chromosome X were associated with increased lymphoid leukemia risk and, mCAs of chromosome Y were linked to potential reduced metabolic disease risk.ConclusionsOur findings demonstrate that a wide range of diseases are potential sequelae of mCAs and highlight the critical importance of careful covariate adjustment in mCA disease association studies

MIRD Pamphlet No 28, Part 2: Comparative Evaluation of MIRDcalc Dosimetry Software Across a Compendium of Diagnostic Radiopharmaceuticals

Radiopharmaceutical dosimetry is usually estimated via organ-level MIRD schema-style formalisms, which form the computational basis for commonly used clinical and research dosimetry software. Recently, MIRDcalc internal dosimetry software was developed to provide a freely available organ-level dosimetry solution that incorporates up-to-date models of human anatomy, addresses uncertainty in radiopharmaceutical biokinetics and patient organ masses, and offers a 1-screen user interface as well as quality assurance tools. The present work describes the validation of MIRDcalc and, secondarily, provides a compendium of radiopharmaceutical dose coefficients obtained with MIRDcalc. Biokinetic data for about 70 currently and historically used radiopharmaceuticals were obtained from the International Commission on Radiological Protection (ICRP) publication 128 radiopharmaceutical data compendium. Absorbed dose and effective dose coefficients were derived from the biokinetic datasets using MIRDcalc, IDAC-Dose, and OLINDA software. The dose coefficients obtained with MIRDcalc were systematically compared against the other software-derived dose coefficients and those originally presented in ICRP publication 128. Dose coefficients computed with MIRDcalc and IDAC-Dose showed excellent overall agreement. The dose coefficients derived from other software and the dose coefficients promulgated in ICRP publication 128 both were in reasonable agreement with the dose coefficients computed with MIRDcalc. Future work should expand the scope of the validation to include personalized dosimetry calculations

MIRD Pamphlet No 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, along with the ability to interpolate between models for patient-specific dosimetry. The software also includes sphere models of various composition for tumor dosimetry. MIRDcalc offers several noteworthy features for organ-level dosimetry, including modeling of blood source regions and dynamic source regions defined by user input, integration of tumor tissues, error propagation, quality control checks, batch processing, and report-preparation capabilities. MIRDcalc implements an immediate, easy-to-use single-screen interface. The MIRDcalc software is available for free download (www.mirdsoft.org) and has been approved by the Society of Nuclear Medicine and Molecular Imaging

Kepler Mission Stellar and Instrument Noise Properties

Kepler Mission results are rapidly contributing to fundamentally new discoveries in both the exoplanet and asteroseismology fields. The data returned from Kepler are unique in terms of the number of stars observed, precision of photometry for time series observations, and the temporal extent of high duty cycle observations. As the first mission to provide extensive time series measurements on thousands of stars over months to years at a level hitherto possible only for the Sun, the results from Kepler will vastly increase our knowledge of stellar variability for quiet solar-type stars. Here we report on the stellar noise inferred on the timescale of a few hours of most interest for detection of exoplanets via transits. By design the data from moderately bright Kepler stars are expected to have roughly comparable levels of noise intrinsic to the stars and arising from a combination of fundamental limitations such as Poisson statistics and any instrument noise. The noise levels attained by Kepler on-orbit exceed by some 50% the target levels for solar-type, quiet stars. We provide a decomposition of observed noise for an ensemble of 12th magnitude stars arising from fundamental terms (Poisson and readout noise), added noise due to the instrument and that intrinsic to the stars. The largest factor in the modestly higher than anticipated noise follows from intrinsic stellar noise. We show that using stellar parameters from galactic stellar synthesis models, and projections to stellar rotation, activity and hence noise levels reproduces the primary intrinsic stellar noise features.Comment: Accepted by ApJ; 26 pages, 20 figure

Kepler-16: A Transiting Circumbinary Planet

We report the detection of a planet whose orbit surrounds a pair of low-mass stars. Data from the Kepler spacecraft reveal transits of the planet across both stars, in addition to the mutual eclipses of the stars, giving precise constraints on the absolute dimensions of all three bodies. The planet is comparable to Saturn in mass and size, and is on a nearly circular 229-day orbit around its two parent stars. The eclipsing stars are 20% and 69% as massive as the sun, and have an eccentric 41-day orbit. The motions of all three bodies are confined to within 0.5 degree of a single plane, suggesting that the planet formed within a circumbinary disk.Comment: Science, in press; for supplemental material see http://www.sciencemag.org/content/suppl/2011/09/14/333.6049.1602.DC1/1210923.Doyle.SOM.pd

Asymptotic Scaling and Infrared Behavior of the Gluon Propagator

The Landau gauge gluon propagator for the pure gauge theory is evaluated on a 32^3x64 lattice with a physical volume of (3.35^3x6.7)fm^4. Comparison with two smaller lattices at different lattice spacings allows an assessment of finite volume and finite lattice spacing errors. Cuts on the data are imposed to minimize these errors. Scaling of the gluon propagator is verified between beta=6.0 and beta=6.2. The tensor structure is evaluated and found to be in good agreement with the Landau gauge form, except at very small momentum values, where some small finite volume errors persist. A number of functional forms for the momentum dependence of the propagator are investigated. The form D(q^2)=D_ir+D_uv, where D_ir(q^2) ~ (q^2+M^2)^-\eta and D_uv is an infrared regulated one-loop asymptotic form, is found to provide an adequate description of the data over the entire momentum region studied - thereby bridging the gap between the infrared confinement region and the ultraviolet asymptotic region. The best estimate for the exponent \eta is 3.2(+0.1/-0.2)(+0.2/-0.3), where the first set of errors represents the uncertainty associated with varying the fitting range, while the second set of errors reflects the variation arising from different choices of infrared regulator in D_uv. Fixing the form of D_uv, we find that the mass parameter M is (1020+/-100)MeV.Comment: 37 pages, RevTeX, 16 postscript figures, 7 gif figures. Revised version accepted for publication in Phys. Rev. D. Model functions and discussion of asymptotic behaviour modified; all model fits have been redone. This paper, including postscript version of all figures, can be found at http://www.physics.adelaide.edu.au/~jskuller/papers