Chimpanzees (Pan troglodytes) navigate to find hidden fruit in a virtual environment

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Prioritising research areas for antibiotic stewardship programmes in hospitals: a behavioural perspective consensus paper

SCOPE: Antibiotic stewardship programmes (ASPs) are necessary in hospitals to improve the judicious use of antibiotics. While ASPs require complex change of key behaviours on individual, team, organisation and policy levels, evidence from the behavioural sciences is underutilised in antibiotic stewardship studies across the world, including high-income countries (HICs). A consensus procedure was performed to propose research priority areas for optimising effective implementation of ASPs in hospital settings, using a behavioural perspective. METHODS: A workgroup for behavioural approaches to ASPs was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). Eighteen clinical and academic specialists in antibiotic stewardship, implementation science and behaviour change from four high-income countries with publicly-funded health care systems (that is Canada, Germany, Norway and the UK), met face-to-face to agree on broad research priority areas using a structured consensus method. QUESTION ADDRESSED AND RECOMMENDATIONS: The consensus process on the 10 identified research priority areas resulted in recommendations that need urgent scientific interest and funding to optimise effective implementation of antibiotic stewardship programmes for hospital inpatients in HICs with publicly-funded health care systems. We suggest and detail, behavioural science evidence-guided research efforts in the following areas: 1) Comprehensively identifying barriers and facilitators to implementing antibiotic stewardship programmes and clinical recommendations intended to optimise antibiotic prescribing; 2) Identifying actors ('who') and actions ('what needs to be done') of antibiotic stewardship programmes and clinical teams; 3) Synthesising available evidence to support future research and planning for antibiotic stewardship programmes; 4) Specifying the activities in current antibiotic stewardship programmes with the purpose of defining a 'control group' for comparison with new initiatives; 5) Defining a balanced set of outcomes and measures to evaluate the effects of interventions focused on reducing unnecessary exposure to antibiotics; 6) Conducting robust evaluations of antibiotic stewardship programmes with built-in process evaluations and fidelity assessments; 7) Defining and designing antibiotic stewardship programmes; 8) Establishing the evidence base for impact of antibiotic stewardship programmes on resistance; 9) Investigating the role and impact of government and policy contexts on antibiotic stewardship programmes; and 10) Understanding what matters to patients in antibiotic stewardship programmes in hospitals. Assessment, revisions and updates of our priority-setting exercise should be considered, at intervals of 2 years. To propose research priority areas in low- and medium income countries (LIMCs), the methodology reported here could be applied

Planck 2018 results. IV. Diffuse component separation

We present full-sky maps of the cosmic microwave background (CMB) and polarized synchrotron and thermal dust emission, derived from the third set of Planck frequency maps. These products have significantly lower contamination from instrumental systematic effects than previous versions. The methodologies used to derive these maps follow closely those described in earlier papers, adopting four methods (Commander, NILC, SEVEM, and SMICA) to extract the CMB component, as well as three methods (Commander, GNILC, and SMICA) to extract astrophysical components. Our revised CMB temperature maps agree with corresponding products in the Planck 2015 delivery, whereas the polarization maps exhibit significantly lower large-scale power, reflecting the improved data processing described in companion papers; however, the noise properties of the resulting data products are complicated, and the best available end-to-end simulations exhibit relative biases with respect to the data at the few percent level. Using these maps, we are for the first time able to fit the spectral index of thermal dust independently over 3 degree regions. We derive a conservative estimate of the mean spectral index of polarized thermal dust emission of beta_d = 1.55 +/- 0.05, where the uncertainty marginalizes both over all known systematic uncertainties and different estimation techniques. For polarized synchrotron emission, we find a mean spectral index of beta_s = -3.1 +/- 0.1, consistent with previously reported measurements. We note that the current data processing does not allow for construction of unbiased single-bolometer maps, and this limits our ability to extract CO emission and correlated components. The foreground results for intensity derived in this paper therefore do not supersede corresponding Planck 2015 products. For polarization the new results supersede the corresponding 2015 products in all respects

Planck 2018 results. III. High Frequency Instrument data processing and frequency maps

This paper presents the High Frequency Instrument (HFI) data processing procedures for the Planck 2018 release. Major improvements in mapmaking have been achieved since the previous 2015 release. They enabled the first significant measurement of the reionization optical depth parameter using HFI data. This paper presents an extensive analysis of systematic effects, including the use of simulations to facilitate their removal and characterize the residuals. The polarized data, which presented a number of known problems in the 2015 Planck release, are very significantly improved. Calibration, based on the CMB dipole, is now extremely accurate and in the frequency range 100 to 353 GHz reduces intensity-to-polarization leakage caused by calibration mismatch. The Solar dipole direction has been determined in the three lowest HFI frequency channels to within one arc minute, and its amplitude has an absolute uncertainty smaller than $0.35\mu$K, an accuracy of order $10^{-4}$. This is a major legacy from the HFI for future CMB experiments. The removal of bandpass leakage has been improved by extracting the bandpass-mismatch coefficients for each detector as part of the mapmaking process; these values in turn improve the intensity maps. This is a major change in the philosophy of "frequency maps", which are now computed from single detector data, all adjusted to the same average bandpass response for the main foregrounds. Simulations reproduce very well the relative gain calibration of detectors, as well as drifts within a frequency induced by the residuals of the main systematic effect. Using these simulations, we measure and correct the small frequency calibration bias induced by this systematic effect at the $10^{-4}$ level. There is no detectable sign of a residual calibration bias between the first and second acoustic peaks in the CMB channels, at the $10^{-3}$ level

Planck 2018 results. XII. Galactic astrophysics using polarized dust emission

We present 353 GHz full-sky maps of the polarization fraction p, angle \u3c8, and dispersion of angles S of Galactic dust thermal emission produced from the 2018 release of Planck data. We confirm that the mean and maximum of p decrease with increasing NH. The uncertainty on the maximum polarization fraction, pmax=22.0% at 80 arcmin resolution, is dominated by the uncertainty on the zero level in total intensity. The observed inverse behaviour between p and S is interpreted with models of the polarized sky that include effects from only the topology of the turbulent Galactic magnetic field. Thus, the statistical properties of p, \u3c8, and S mostly reflect the structure of the magnetic field. Nevertheless, we search for potential signatures of varying grain alignment and dust properties. First, we analyse the product map S 7p, looking for residual trends. While p decreases by a factor of 3--4 between NH=1020 cm 122 and NH=2 71022 cm 122, S 7p decreases by only about 25%, a systematic trend observed in both the diffuse ISM and molecular clouds. Second, we find no systematic trend of S 7p with the dust temperature, even though in the diffuse ISM lines of sight with high p and low S tend to have colder dust. We also compare Planck data with starlight polarization in the visible at high latitudes. The agreement in polarization angles is remarkable. Two polarization emission-to-extinction ratios that characterize dust optical properties depend only weakly on NH and converge towards the values previously determined for translucent lines of sight. We determine an upper limit for the polarization fraction in extinction of 13%, compatible with the pmax observed in emission. These results provide strong constraints for models of Galactic dust in diffuse gas

Planck 2018 results. XII. Galactic astrophysics using polarized dust emission

We present 353 GHz full-sky maps of the polarization fraction $p$, angle $\psi$, and dispersion of angles $S$ of Galactic dust thermal emission produced from the 2018 release of Planck data. We confirm that the mean and maximum of $p$ decrease with increasing $N_H$. The uncertainty on the maximum polarization fraction, $p_\mathrm{max}=22.0$% at 80 arcmin resolution, is dominated by the uncertainty on the zero level in total intensity. The observed inverse behaviour between $p$ and $S$ is interpreted with models of the polarized sky that include effects from only the topology of the turbulent Galactic magnetic field. Thus, the statistical properties of $p$, $\psi$, and $S$ mostly reflect the structure of the magnetic field. Nevertheless, we search for potential signatures of varying grain alignment and dust properties. First, we analyse the product map $S \times p$, looking for residual trends. While $p$ decreases by a factor of 3--4 between $N_H=10^{20}$ cm$^{-2}$ and $N_H=2\times 10^{22}$ cm$^{-2}$, $S \times p$ decreases by only about 25%, a systematic trend observed in both the diffuse ISM and molecular clouds. Second, we find no systematic trend of $S \times p$ with the dust temperature, even though in the diffuse ISM lines of sight with high $p$ and low $S$ tend to have colder dust. We also compare Planck data with starlight polarization in the visible at high latitudes. The agreement in polarization angles is remarkable. Two polarization emission-to-extinction ratios that characterize dust optical properties depend only weakly on $N_H$ and converge towards the values previously determined for translucent lines of sight. We determine an upper limit for the polarization fraction in extinction of 13%, compatible with the $p_\mathrm{max}$ observed in emission. These results provide strong constraints for models of Galactic dust in diffuse gas

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 genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function