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Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Intrauterine or fetal growth restriction (IUGR) is a major complication of pregnancy and leads to significant perinatal morbidities and mortality. Typically, induction of IUGR in animals involves the complete occlusion or ablation of vessels to the uterus or placenta, acutely impairing blood flow and fetal growth, usually with high fetal loss. We aimed to produce a model of reduced fetal growth in the spiny mouse with minimal fetal loss. At 27 days gestational age (term is 38–39 days), a piece of silastic tubing was placed around the left uterine artery to prevent the further increase of uterine blood flow with advancing gestation to induce IUGR (occluded). Controls were generated from sham surgeries without placement of the tubing. Dams were humanely euthanized at 37 days gestational age and all fetuses and placentas were weighed and collected. Of the 17 dams that underwent surgery, 15 carried their pregnancies to 37 days gestational age and 95% of fetuses survived to this time. The difference in fetal body weight between occluded and control was ~21% for fetuses in the left uterus side: there were no differences for fetuses in the right uterus side. Offspring from the occluded group had significantly lower brain, liver, lung, kidney and carcass weights compared with shams. Preventing the gestation-related increase of uterine blood flow induced significant growth restriction in the fetal spiny mouse, with minimal fetal loss. This technique could be readily adapted for other small animal.
Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.
A K-band (18-25 GHz) reflected-wave ruby maser (Moore and Clauss 1979) has been borrowed from the National Radio Astronomy Observatory for radio astronomy use on the NASA 64-m antenna of the Deep Space Network at the Tidbinbilla Tracking Station, near Canberra. The purpose of the installation is to provide additional sensitive spectral line, continuum, and VLBI capabilities in the southern hemisphere. Previous measurements at 22.3 GHz (λ = 13.5 mm) determined that the Tidbinbilla 64-m antenna has a peak aperture efficiency of ˜22%, a well-behaved beam shape and consistent pointing (Fourikis and Jauncey 1979). Before installing the maser on the antenna a cooled (circulator) switch was added to provide a beam-switching capability, and a spectral line receiver following the maser was incorporated. The system was assembled and tested at JPL in late 1980 and installed at Tidbinbilla early in 1981. We give here a brief description and present some of the first line observations made in February and March 1981. Extensive line and continuum observations are planned with the present system and a program is under way to determine the telescope pointing characteristics.
To assess alcoholic beverage intake among Australian adults and its contribution to dietary energy intake.
Secondary analysis of a national dietary survey using 24 h dietary recall.
Australian National Nutrition and Physical Activity Survey (NNPAS) conducted from May 2011 to June 2012.
Adults (n 9341) aged 19 years and over.
On the day preceding the survey, 32·8% of Australian adults consumed one or more alcoholic drinks. The median contribution to total energy intake for consumers did not differ significantly between males and females (13·7% and 12·9%, respectively; P=0·10). The prevalence of consumption of alcoholic drinks on Friday, Saturday and Sunday was 38·8 (95% CI 37·1, 40·5)%, higher than the other days (28·6 (95% CI 27·5, 29·8)%). Consumers had a median daily intake of 4·0 standard drinks on the weekend compared with 3·0 standard drinks during the week (P<0·001). Beer was the most commonly consumed alcoholic beverage for men and white wine for women. The highest prevalence of alcoholic beverage intake occurred in the highest quintile of adjusted household income (42·7 (95% CI 40·4, 45·0)%) and the ‘overweight’ BMI category (40·3 (95% CI 38·5, 42·0)%). Alcoholic beverage intake among consumers was significantly different by household income quintile (median 3·84 (highest) v. 3·05 standard drinks (lowest); P<0·05) and by waist circumference category (median 4·09 standard drinks (highest)).
Alcoholic drinks contribute substantially to the dietary energy intake of Australian adults. The type and pattern of consumption of alcoholic beverage intake should be considered in the development of strategies to improve dietary intake.
Cooperative breeders are species in which individuals beyond a pair assist in the production of young in a single brood or litter. Although relatively rare, cooperative breeding is widespread taxonomically and continues to pose challenges to our understanding of the evolution of cooperation and altruistic behavior. Bringing together long-term studies of cooperatively breeding birds, mammals, and fish, this volume provides a synthesis of current studies in the field. The chapters are organised by individual studies of particular species or (in the case of mole-rats) two closely related cooperatively breeding species. Each focuses not only on describing behavior and ecology but also on testing evolutionary hypotheses for the form and function of the diverse and extraordinary cooperative breeding lifestyles that have been discovered. This unique and comprehensive text will be of interest to graduate students and researchers of behavioral ecology and the evolution of cooperation.
Completing the census of AGN in the Universe is the key to understanding the cosmic evolution of supermassive black holes (SMBH) and galaxies, and to resolving the spectrum of the X-ray background (XRB). However, a large population of AGN, especially the heavily obscured, Compton-thick AGN, are still missing from even the deepest X-ray surveys. The infrared spectra energy distribution (SED) of distant star-forming galaxies can reveal the presence of bright AGN activity. Using some of the deepest infrared, X-ray and radio data available in the GOODS fields, we identify a population of infrared bright quasars at redshift z ~ 2, which are often missed in the X-ray band. Amongst these sources the number of obscured and heavily-obscured quasars is much higher than those previously found in several X-ray and optical selected samples. A unique view on these heavily-obscured quasars is now given at high energies by NuSTAR. I will present the first NuSTAR detection of a heavily obscured quasar at z 2. This source is a potential archetype of the heavily-obscured high-z AGN in which most of the black hole growth is happening, that can explain the mysterious missing fraction of the XRB.
Coronary artery disease is a major problem worldwide causing 7.2 million deaths worldwide annually, resulting from vascular occlusion, myocardial infarction and its complications. Stent implantation is a percutaneous interventional procedure that mitigates vessel stenosis, providing mechanical support within the artery. However, stenting causes physical damage to the arterial wall. It is well accepted that a valuable route to reduce in-stent re-stenosis can be based on promoting cell response to nano-structured stainless steel (SS) surfaces such as, for example, by patterning nano-pits in SS. In this regard patterning by Focussed Ion-Beam (FIB) milling offers several advantages for flexible prototyping (i) practically any substrate material that is able to withstand high vacuum conditions of the microscope chamber can be used, (ii) there is high flexibility in the obtainable shapes and geometries by modulating the ion beam current and the patterning conditions, (iii) reduced complexity of the pattering process e.g. it is a single-step process with a possibility of real-time monitoring of the milling progression. On the other hand FIB patterning of polycrystalline metals is greatly influenced by channelling effects and re-deposition. Correlative microscopy methods present an opportunity to study such effects comprehensively and derive structure-property understanding that is important for developing improved pattering. In this report we present a FIB patterning protocol for nano-structuring features (concaves) ordered in rectangular arrays on pre-polished 316L Stainless Steel (SS) surfaces. An investigation based on correlative microscopy approach of the size, shape and depth of the developed arrays in relation to the crystal orientation of the underlying SS domains, is presented. The correlative microscopy protocol is based on cross-correlation of top-view Scanning Electron Microscopy (SEM), Electron Backscattered Diffraction (EBSD), and Atomic Force Microscopy (AFM).Various dose tests were performed, aiming at improved productivity by preserving nano-size accuracy of the patterned process. The optimal FIB patterning conditions for achieving reasonably high throughput (patterned rate of about 0.03 mm2 per hour) and nano-size accuracy in dimensions and shapes of the features, are discussed as well.
We report the fabrication and characterisation of the first graphene ring micro electrodes, formed by dip coating fibre optics with subsequently reduced graphite oxide. The behaviour of the so-formed Graphene RIng Micro Electrodes (GRIMEs) is studied using the ferricyanide probe redox system while electrode thicknesses is assessed using established electrochemical methods. A ring electrode of ∼73 nm thickness is produced on 220 μm diameter fibre optics, corresponding to an inner to outer radius ratio of >0.999, so allowing for use of extant analytical descriptions of very thin ring micro electrodes in data analysis. GRIMEs are highly reliable (current response invariant over >3000 scans) with the microring design allowing for efficient use of electrochemically active graphene edge sites. Further, the associated nA scale currents neatly obviate issues relating to the high resistivity of undoped graphene. Thus, the use of graphene in ring micro electrodes improves the reliability of existing micro electrode designs and expands the range of use of graphene-based electrochemical devices.