Heritability and correlations among learning and inhibitory control traits

To understand the evolution of cognitive abilities, we need to understand both how selection acts upon them and their genetic (co)variance structure. Recent work suggests that there are fitness consequences for free-living individuals with particular cognitive abilities. However, our current understanding of the heritability of these abilities is restricted to domesticated species subjected to artificial selection. We investigated genetic variance for, and genetic correlations among four cognitive abilities: inhibitory control, visual and spatial discrimination, and spatial ability, measured on >450 pheasants, Phasianus colchicus, over four generations. Pheasants were reared in captivity but bred from adults that lived in the wild and hence, were subject to selection on survival. Pheasant chicks are precocial and were reared without parents, enabling us to standardize environmental and parental care effects. We constructed a pedigree based on 15 microsatellite loci and implemented animal models to estimate heritability. We found moderate heritabilities for discrimination learning and inhibitory control (h2 = 0.17–0.23) but heritability for spatial ability was low (h2 = 0.09). Genetic correlations among-traits were largely positive but characterized by high uncertainty and were not statistically significant. Principle component analysis of the genetic correlation matrix estimate revealed a leading component that explained 69% of the variation, broadly in line with expectations under a general intelligence model of cognition. However, this pattern was not apparent in the phenotypic correlation structure which was more consistent with a modular view of animal cognition. Our findings highlight that the expression of cognitive traits is influenced by environmental factors which masks the underlying genetic structure

The effect of active galactic nuclei on the cold interstellar medium in distant star-forming galaxies

In the framework of a systematic study with the ALMA interferometer of IR-selected main-sequence and starburst galaxies at z ∼ 1 − 1.7 at typical ∼1″ resolution, we report on the effects of mid-IR- and X-ray-detected active galactic nuclei (AGN) on the reservoirs and excitation of molecular gas in a sample of 55 objects. We find widespread detectable nuclear activity in ∼30% of the sample. The presence of dusty tori influences the IR spectral energy distribution of galaxies, as highlighted by the strong correlation among the AGN contribution to the total IR luminosity budget (fAGN = LIR,  AGN/LIR), its hard X-ray emission, and the Rayleigh-Jeans to mid-IR (S1.2 mm/S24 μm) observed color, with evident consequences on the ensuing empirical star formation rate estimates. Nevertheless, we find only marginal effects of the presence and strength of AGN on the carbon monoxide CO (J = 2, 4, 5, 7) or neutral carbon ([C I](3P1  −  3P0), [C I](3P2  −  3P1)) line luminosities and on the derived molecular gas excitation as gauged by line ratios and the full spectral line energy distributions. The [C I] and CO emission up to J = 5, 7 thus primarily traces the properties of the host in typical IR luminous galaxies. However, our analysis highlights the existence of a large variety of line luminosities and ratios despite the homogeneous selection. In particular, we find a sparse group of AGN-dominated sources with the highest LIR,  AGN/LIR,  SFR ratios, ≳3, that are more luminous in CO (5−4) than what is predicted by the L′CO(5-4)−LIR, SFR relation, which might be the result of the nuclear activity. For the general population, our findings translate into AGN having minimal effects on quantities such as gas and dust fractions and star formation efficiencies. If anything, we find hints of a marginal tendency of AGN hosts to be compact at far-IR wavelengths and to display 1.8 times larger dust optical depths. In general, this is consistent with a marginal impact of the nuclear activity on the gas reservoirs and star formation in average star-forming AGN hosts with LIR > 5 × 1011 L⊙, typically underrepresented in surveys of quasars and submillimeter galaxies

Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model

Background: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. Methods: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). Results: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapy’s ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. Discussion: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents

Sex Segregation and Salary Structure in Academia

This article reports a study of aggregate unit salary levels, within a major research university. We analyze these salary levels, as they are influenced by unit sex composition, and modified by unit attainment levels—where unit refers to the departments, colleges and schools, and other academic divisions of the university. We investigate three central issues of sex and salary, previously overlooked in salary studies of academic employees: Do high proportions of women depress men's unit salary levels ("competition" hypothesis)? Are women's salary levels higher in male-dominated, and lower in female-dominated, units ("concentration" hypothesis)? Are men salary-compensated for working with women ("compensation" hypothesis)? The findings support none of these hypotheses. Rather, the relationship between unit sex composition and salary rests upon the connection between units' composition and attainment levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69126/2/10.1177_073088848100800103.pd

Effect of Adopting the New Race-Free 2021 Chronic Kidney Disease Epidemiology Collaboration Estimated Glomerular Filtration Rate Creatinine Equation on Racial Differences in Kidney Disease Progression among People with Human Immunodeficiency Virus: An Observational Study

Background: The impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown. Methods: We defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models. Results: With the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI],. 73-.82), an equal risk of progressing from stage 2 to 3 (1.00;. 92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants. Conclusions: The original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD

Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules : the SPUtNIk diagnostic accuracy study and economic modelling

Background Current pathways recommend positron emission tomography–computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach. Objectives To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography–computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies. Design Multicentre comparative accuracy trial. Setting Secondary or tertiary outpatient settings at 16 hospitals in the UK. Participants Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included. Interventions Baseline positron emission tomography–computerised tomography and dynamic contrast-enhanced computer tomography with 2 years’ follow-up. Main outcome measures Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography–computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography. Results A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography–computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography–computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography–computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography–computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51). Limitations The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening. Conclusions Findings from this research indicate that positron emission tomography–computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography–dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a ‘watch and wait’ policy may be an approach to consider. Future work Integration of the dynamic contrast-enhanced component into the positron emission tomography–computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol. Study registration This study is registered as PROSPERO CRD42018112215 and CRD42019124299, and the trial is registered as ISRCTN30784948 and ClinicalTrials.gov NCT02013063

Planck early results XVII : Origin of the submillimetre excess dust emission in the Magellanic Clouds

Peer reviewe

Planck early results. XVII. Origin of the submillimetre excess dust emission in the Magellanic Clouds

The integrated spectral energy distributions (SED) of the Large Magellanic Cloud (LMC) and SmallMagellanic Cloud (SMC) appear significantly flatter than expected from dust models based on their far-infrared and radio emission. The still unexplained origin of this millimetre excess is investigated here using the Planck data. The integrated SED of the two galaxies before subtraction of the foreground (Milky Way) and background (CMB fluctuations) emission are in good agreement with previous determinations, confirming the presence of the millimetre excess. In the context of this preliminary analysis we do not propose a full multi-component fitting of the data, but instead subtract contributions unrelated to the galaxies and to dust emission. The background CMB contribution is subtracted using an internal linear combination (ILC) method performed locally around the galaxies. The foreground emission from the Milky Way is subtracted as a Galactic Hi template, and the dust emissivity is derived in a region surrounding the two galaxies and dominated by Milky Way emission. After subtraction, the remaining emission of both galaxies correlates closely with the atomic and molecular gas emission of the LMC and SMC. The millimetre excess in the LMC can be explained by CMB fluctuations, but a significant excess is still present in the SMC SED. The Planck and IRAS–IRIS data at 100 μm are combined to produce thermal dust temperature and optical depth maps of the two galaxies. The LMC temperature map shows the presence of a warm inner arm already found with the Spitzer data, but which also shows the existence of a previously unidentified cold outer arm. Several cold regions are found along this arm, some of which are associated with known molecular clouds. The dust optical depth maps are used to constrain the thermal dust emissivity power-law index (β). The average spectral index is found to be consistent with β =1.5 and β =1.2 below 500 μm for the LMC and SMC respectively, significantly flatter than the values observed in the Milky Way. Also, there is evidence in the SMC of a further flattening of the SED in the sub-mm, unlike for the LMC where the SED remains consistent with β =1.5. The spatial distribution of the millimetre dust excess in the SMC follows the gas and thermal dust distribution. Different models are explored in order to fit the dust emission in the SMC. It is concluded that the millimetre excess is unlikely to be caused by very cold dust emission and that it could be due to a combination of spinning dust emission and thermal dust emission by more amorphous dust grains than those present in our Galaxy