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Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2).
Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis.
In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3–7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI.
Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.
Body condition score (BCS) is a subjective assessment of the proportion of body fat an animal possesses and is independent of frame size. There is a growing awareness of the importance of mature animal live-weight given its contribution to the overall costs of production of a sector. Because of the known relationship between BCS and live-weight, strategies to reduce live-weight could contribute to the favouring of animals with lesser body condition. The objective of the present study was to estimate the average difference in live-weight per incremental change in BCS, measured subjectively on a scale of 1 to 5. The data used consisted of 19 033 BCS and live-weight observations recorded on the same day from 7556 ewes on commercial and research flocks; the breeds represented included purebred Belclare (540 ewes), Charollais (1484 ewes), Suffolk (885 ewes), Texel (1695 ewes), Vendeen (140 ewes), as well as, crossbreds (2812 ewes). All associations were quantified using linear mixed models with the dependent variable of live-weight; ewe parity was included as a random effect. The independent variables were BCS, breed (n=6), stage of the inter-lambing interval (n=6; pregnancy, lambing, pre-weaning, at weaning, post-weaning and mating) and parity (1, 2, 3, 4 and 5+). In addition, two-way interactions were used to investigate whether the association between BCS and live-weight differed by parity, a period of the inter-lambing interval or breed. The association between BCS and live-weight differed by parity, by a period of the inter-lambing interval and by breed. Across all data, a one-unit difference in BCS was associated with 4.82 (SE=0.08) kg live-weight, but this differed by parity from 4.23 kg in parity 1 ewes to 5.82 kg in parity 5+ ewes. The correlation between BCS and live-weight across all data was 0.48 (0.47 when adjusted for nuisance factors in the statistical model), but this varied from 0.48 to 0.53 by parity, from 0.36 to 0.63 by stage of the inter-lambing interval and from 0.41 to 0.62 by breed. Results demonstrate that consideration should be taken of differences in BCS when comparing ewes on live-weight as differences in BCS contribute quite substantially to differences in live-weight; moreover, adjustments for differences in BCS should consider the population stratum, especially breed.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
Accurate genomic analyses are predicated on access to a large quantity of accurately genotyped and phenotyped animals. Because the cost of genotyping is often less than the cost of phenotyping, interest is increasing in generating genotypes for phenotyped animals. In some instances this may imply the requirement to genotype older animals with greater phenotypic information content. Biological material for these older informative animals may, however, no longer exist. The objective of the present study was to quantify the ability to impute 11 129 single nucleotide polymorphism (SNP) genotypes of non-genotyped animals (in this instance sires) from the genotypes of their progeny with or without including the genotypes of the progenys’ dams (i.e. mates of the sire to be imputed). The impact on the accuracy of genotype imputation by including more progeny (and their dams’) genotypes in the imputation reference population was also quantified. When genotypes of the dams were not available, genotypes of 41 sires with at least 15 genotyped progeny were used for the imputation; when genotypes of the dams were available, genotypes of 21 sires with at least 10 genotyped progeny were used for the imputation. Imputation was undertaken exploiting family and population level information. The mean and variability in the proportion of genotypes per individual that could not be imputed reduced as the number of progeny genotypes used per individual increased. Little improvement in the proportion of genotypes that could not be imputed was achieved once genotypes of seven progeny and their dams were used or genotypes of 11 progeny without their respective dam’s genotypes were used. Mean imputation accuracy per individual (depicted by both concordance rates and correlation between true and imputed) increased with increasing progeny group size. Moreover, the range in mean imputation accuracy per individual reduced as more progeny genotypes were used in the imputation. If the genotype of the mate of the sire was also used, high accuracy of imputation (mean genotype concordance rate per individual of 0.988), with little additional benefit thereafter, was achieved with seven genotyped progeny. In the absence of genotypes on the dam, similar imputation accuracy could not be achieved even using genotypes on up to 15 progeny. Results therefore suggest, at least for the SNP density used in the present study, that it is possible to accurately impute the genotypes of a non-genotyped parent from the genotypes of its progeny and there is a benefit of also including the genotype of the sire’s mate (i.e. dam of the progeny).
The objective of the present study was to quantify the extent of genetic variation in three health-related traits namely dagginess, lameness and mastitis, in an Irish sheep population. Each of the health traits investigated pose substantial welfare implications as well as considerable economic costs to producers. Data were also available on four body-related traits, namely body condition score (BCS), live weight, muscle depth and fat depth. Animals were categorised as lambs (<365 days old) or ewes (⩾365 days old) and were analysed both separately and combined. After edits, 39 315 records from 264 flocks between the years 2009 and 2015 inclusive were analysed. Variance components were estimated using animal linear mixed models. Fixed effects included contemporary group, represented as a three-way interaction between flock, date of inspection and animal type (i.e. lamb, yearling ewe (i.e. females ⩾365 days but <730 days old that have not yet had a recorded lambing) or ewe), animal breed proportion, coefficients of heterosis and recombination, animal gender (lambs only), animal parity (ewes only; lambs were assigned a separate ‘parity’) and the difference in age of the animal from the median of the respective parity/age group. An additive genetic effect and residual effect were both fitted as random terms with maternal genetic and non-genetic components also considered for traits of the lambs. The direct heritability of dagginess was similar across age groups (0.14 to 0.15), whereas the direct heritability of lameness ranged from 0.06 (ewes) to 0.12 (lambs). The direct heritability of mastitis was 0.04. For dagginess, 13% of the phenotypic variation was explained by dam litter, whereas the maternal heritability of dagginess was 0.05. The genetic correlation between ewe and lamb dagginess was 0.38; the correlation between ewe and lamb lameness was close to zero but was associated with a large standard error. Direct genetic correlations were evident between dagginess and BCS in ewes and between lameness and BCS in lambs. The present study has demonstrated that ample genetic variation exists for all three health traits investigated indicating that genetic improvement is indeed possible.
There are now significant data to support the hypothesis that early life nutrition in the fetus, infant and young child can have profound effects on long-term health. This review considers some of this evidence with specific reference to the current burden of disease in Australia and New Zealand. As the findings of further research become available, recommendations on optimizing early life nutrition should be formulated and made widely available as part of the preventative health policy agenda in both Australia and New Zealand.
Three spatially extended travelling wave exact coherent states, together with one spanwise-localised state, are presented for channel flow. Two of the extended flows are derived by homotopy from solutions to the problem of channel flow subject to a spanwise rotation investigated by Wall & Nagata (J. Fluid Mech., vol. 727, 2013, pp. 523–581). Both these flows are asymmetric with respect to the channel centreplane, and feature streaky structures in streamwise velocity flanked by staggered vortical structures. One of these flows features two streak/vortex systems per spanwise wavelength, while the other features one such system. The former substantially reduces the value of the lowest Reynolds number at which channel flow solutions ,other than the basic flow, are known to exist down to 665. The third flow has, in contrast, half-turn rotational symmetry about a streamwise axis through a point on the channel centreplane, and is found to be the flow from which one of the asymmetric flows bifurcates in a symmetry-breaking bifurcation. This flow is found to exist on an isolated bifurcation branch, whose upper and lower branches both lie on the boundary basin separating initial conditions that lead to turbulent events, and those that directly decay back to laminar flow. The structure of this flow, in which the disturbance to the basic flow is concentrated in a core region in a spanwise period, allowed the derivation of a corresponding spanwise-localised flow, which is also discussed.
Increasing phosphorus (P) fertilizer use efficiency in grassland is desirable, since uncertainty exists over the reserves of finite phosphate rock and its future availability. This necessitates revaluation of the current P fertilizer recommendations for grassland to examine the potential to increase fertilizer P efficiency. The present paper reports results from a long-term grassland P experiment (17 years) on two sites in which annual P fertilizer application rates were 0, 15, 30 and 45 kg P/ha/year. The effect of P fertilizer rate on herbage production and mineral concentration in herbage were investigated in addition to the soil test P (Morgan's) trends and P balance over the duration of the experiment for each rate of P fertilizer. The results showed that the P response to herbage yield and P concentration was similar on both sites. The response of herbage yield to P fertilizer was limited to harvests early in the growing season. The P concentration in herbage was lower in mid-season than in spring or autumn. Annual P fertilizer applications > 30 kg P/ha/year were required to maintain soil P levels at their initial levels over the duration of the experiment.
Antarctic and Southern Ocean science is vital to understanding natural variability, the processes that govern global change and the role of humans in the Earth and climate system. The potential for new knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic community came together to ‘scan the horizon’ to identify the highest priority scientific questions that researchers should aspire to answer in the next two decades and beyond. Wide consultation was a fundamental principle for the development of a collective, international view of the most important future directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific questions through structured debate, discussion, revision and voting. Questions were clustered into seven topics: i) Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world, iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond, and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require innovative experimental designs, novel applications of technology, invention of next-generation field and laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples. Sustained year-round access to Antarctica and the Southern Ocean will be essential to increase winter-time measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the Earth System, and provide predictions at spatial and temporal resolutions useful for decision making. A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration, will be essential as no scientist, programme or nation can realize these aspirations alone.
Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents.
To assess the efficacy of aripiprazole once-monthly compared with oral aripiprazole for maintenance treatment of schizophrenia.
A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to aripiprazole once-monthly 400 mg, oral aripiprazole (10–30 mg/day) or aripiprazole once-monthly 50mg (a dose below the therapeutic threshold for assay sensitivity). (Trial registration: clinicaltrials.gov, NCT00706654.)
A total of 1118 patients were screened, and 662 responders to oral aripiprazole were randomised. Kaplan–Meier estimated impending relapse rates at week 26 were 7.12% for aripiprazole once-monthly 400mg and 7.76% for oral aripiprazole. This difference (−0.64%, 95% CI −5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments were superior to aripiprazole once-monthly 50mg (21.80%, P⩽0.001).
Aripiprazole once-monthly 400mg was non-inferior to oral aripiprazole, and the reduction in Kaplan–Meier estimated impending relapse rate at week 26 was statistically significant v. aripiprazole once-monthly 50 mg.
Mineralized soil nitrogen (N) is an important source of N for grassland production. Some soils can supply large quantities of plant-available N through mineralization of soil organic matter. Grass grown on such soils require less fertilizer N applications per unit yield. A reliable, accurate and user-friendly method to account for soil N supply potential across a large diversity of soils and growing conditions is needed to improve N management and N recommendations over time. In the current study, the effectiveness of chemical N tests and soil properties to predict soil N supply for grass uptake across 30 Irish soil types varying in N supply potential was investigated under controlled environmental conditions. The Illinois soil N test (ISNT) combined with soil C : N ratio provided a good estimate of soil N supply in soils with low residual mineral N. Total oxidized N (TON) had the largest impact on grass dry matter (DM) yield and N uptake across the 30 soil types, declining in its influence in later growth periods. This reflected the high initial mineral N levels in these soils, which declined over time. In the current study, a model with ISNT-N, C : N and TON (log TON) best explained variability in grass DM yield and N uptake. All three rapid chemical soil tests could be performed routinely on field samples to provide an estimate of soil N supply prior to making N fertilizer application decisions. It can be concluded that these soil tests, through their assessment of soil N supply potential, can be effective tools for N management on grassland; however, field studies are needed to evaluate this under more diverse growing conditions.
Excellent reproductive performance in both males and females is fundamental to profitable dairy and beef production systems. In this review we undertook a meta-analysis of genetic parameters for female reproductive performance across 55 dairy studies or populations and 12 beef studies or populations as well as across 28 different studies or populations for male reproductive performance. A plethora of reproductive phenotypes exist in dairy and beef cattle and a meta-analysis of the literature suggests that most of the female reproductive traits in dairy and beef cattle tend to be lowly heritable (0.02 to 0.04). Reproductive-related phenotypes in male animals (e.g. semen quality) tend to be more heritable than female reproductive phenotypes with mean heritability estimates of between 0.05 and 0.22 for semen-related traits with the exception of scrotal circumference (0.42) and field non-return rate (0.001). The low heritability of reproductive traits, in females in particular, does not however imply that genetic selection cannot alter phenotypic performance as evidenced by the decline until recently in dairy cow reproductive performance attributable in part to aggressive selection for increased milk production. Moreover, the antagonistic genetic correlations among reproductive traits and both milk (dairy cattle) and meat (beef cattle) yield is not unity thereby implying that simultaneous genetic selection for both increased (milk and meat) yield and reproductive performance is indeed possible. The required emphasis on reproductive traits within a breeding goal to halt deterioration will vary based on the underlying assumptions and is discussed using examples for Ireland, the United Kingdom and Australia as well as quantifying the impact on genetic gain for milk production. Advancements in genomic technologies can aid in increasing the accuracy of selection for especially reproductive traits and thus genetic gain. Elucidation of the underlying genomic mechanisms for reproduction could also aid in resolving genetic antagonisms. Past breeding programmes have contributed to the deterioration in reproductive performance of dairy and beef cattle. The tools now exist, however, to reverse the genetic trends in reproductive performance underlying the observed phenotypic trends.
The current study investigated the coupling of groundwater and surface water nitrogen (N) dynamics over 3 years, and considered intensive agricultural land-management influences over this period where the risk of N loss to water was considered high. Groundwater N (as nitrate) was monitored monthly in different strata and zones in four hillslopes, two in each of two agricultural catchments of c. 10 km2, and stream water N flux was monitored sub-hourly in the catchment outlets. Field nutrient sources were connected to surface water via groundwater; the groundwater along hillslopes was seen to be influenced spatially and temporally by management, geology and weather as observed in the concentration variability of nitrate in groundwater. Based on spatio-temporal averages of nitrate-N concentration, groundwater status was considered good (at least below a maximum acceptable concentration (MAC) of 11·3 mg/l). However, zones coincident with land-use change (ploughing and reseeding, typical of a management event in intensive landscapes), showed high spatio-temporal variability in nitrate-N concentration, exceeding the MAC temporarily, before recovering. This spatio-temporal variability highlighted the need for insight into these differences when interpreting groundwater quality data from a limited number of basin-scale sampling points and occasions. In both catchments the 3-year mean nitrate-N concentration in stream water was similar to the spatio-temporal mean concentration in groundwater. The magnitude and variability of loads, however, were more related to changes in annual runoff rather than changes in annual groundwater nitrate-N status. In one wet year, nitrate-N loads exceeded 48 kg/ha from an Arable catchment and 45 kg/ha from a grassland catchment (close to double the loss in a dry year).
Although the cadmium chloride treatment is an essential process for high efficiency thin film cadmium telluride photovoltaic devices, the precise mechanisms involved that improve the cadmium telluride layer are not well understood. In this investigation we apply advanced micro-structural characterization techniques to study the effect of varying the time of the cadmium chloride annealing treatment on the micro-structure of cadmium telluride solar cells deposited by close spaced sublimation (CSS) and relate this to cell performance. A range of techniques has been used to observe the morphological changes to the micro-structure as well as the chemical and crystallographic changes as a function of treatment parameters. Electrical tests that link the device performance with the micro-structural properties of the cells have also been undertaken. Techniques used include Transmission Electron Microscopy (TEM) for sub-grain analysis and XPS for composition-depth profiling. The study provides a new insight in to the mechanisms involved in the initiation and the subsequent complete re-crystallization of the cadmium telluride layer.
A phenotype describes the outcome of the interacting development between the genotype of an individual and its specific environment throughout life. Animal breeding currently exploits large data sets of phenotypic and pedigree information to estimate the genetic merit of animals. Here we describe rapid, low-cost phenomic tools for dairy cattle. We give particular emphasis to infrared spectroscopy of milk because the necessary spectral data are already routinely available on milk samples from individual cows and herds, and therefore the operational cost of implementing such a phenotyping strategy is minimal. The accuracy of predicting milk quality traits from mid-infrared spectroscopy (MIR) analysis of milk, although dependent on the trait under investigation, is particularly promising for differentiating between good and poor-quality dairy products. Many fatty acid concentrations in milk, and in particular saturated fatty acid content, can be very accurately predicted from milk MIR. These results have been confirmed in many international populations. Albeit from only two studied populations investigated in the RobustMilk project, milk MIR analysis also appears to be a reasonable predictor of cow energy balance, a measure of animal robustness; high accuracy of prediction was not expected as the gold standard method of measuring energy balance in those populations was likely to contain error. Because phenotypes predicted from milk MIR are available routinely from milk testing, longitudinal data analyses could be useful to identify animals of superior genetic merit for milk quality and robustness, as well as for monitoring changes in milk quality and robustness because of management, while simultaneously accounting for the genetic merit of the animals. These sources of information can be very valuable input parameters in decision-support tools for both milk producers and processors.
Genetic improvement is easy when selecting for one heritable and well-recorded trait at a time. Many industrialised national dairy herds have overall breeding indices that incorporate a range of traits balanced by their known or estimated economic value. Future breeding goals will contain more non-production traits and, in the context of this paper, traits associated with human health and cow robustness. The definition of Robustness and the traits used to predict it are currently fluid; however, the use of mid-infrared reflectance spectroscopic analysis of milk will help to create new phenotypes on a large scale that can be used to improve the human health characteristics of milk and the robustness of cows producing it. This paper describes the state-of-the-art in breeding strategies that include animal robustness (mainly energy status) and milk quality (as described by milk fatty acid profile), with particular emphasis on the research results generated by the FP7-funded RobustMilk project
Three-dimensional exact, finite-amplitude solutions are presented for the problem of channel flow subject to a system rotation about a spanwise axis. The solutions are of travelling wave form, and may bifurcate as tertiary flows from the two-dimensional streamwise-independent secondary flow, or as secondary flows directly from the basic flow. For the tertiary flows, we consider solutions of spanwise superharmonic and subharmonic type. We distinguish flows on the basis of symmetry, originating eigenmode and major solution branch, and thus identify 15 distinct flows: 5 superharmonic tertiary, 5 subharmonic tertiary and 5 secondary flows. The tertiary flows all feature a single layer of vortical structures in the spanwise–wall-normal plane, the secondary flows feature single-, double-, triple- or quadruple-layer flow structures in this plane. All flows feature low-speed streamwise-orientated streaks in the streamwise velocity component and/or pulses of low-speed streamwise velocity. The streaks may be sinusoidal or varicose. Sinusoidal streaks are flanked by staggered streamwise vortices, varicose streaks and pulses are flanked by aligned vortices. A comparison with previous simulation and experimental studies finds that the simplest three-dimensional flows observed previously correspond to superharmonic tertiary flows bifurcating from the upper branch of the secondary flow. The mean absolute vorticity of the present flows is also considered. A flattening of the profile of this vorticity is observed in the central region of the channel for two-dimensional secondary and many of the three-dimensional flows, with two-step profiles also observed. This phenomenon is attributed to mixing of the vorticity across zones of the channel in which streamwise vortex structures exist, and is demonstrated by a two-dimensional model. The phenomenon appears to be distinct to that observed in fully turbulent rotating channel flows.
The future of centimetre and metre-wave astronomy lies with the Square Kilometre Array (SKA), a telescope under development by a consortium of 17 countries that will be 50 times more sensitive than any existing radio facility. Most of the key science for the SKA will be addressed through large-area imaging of the Universe at frequencies from a few hundred MHz to a few GHz. The Australian SKA Pathfinder (ASKAP) is a technology demonstrator aimed in the mid-frequency range, and achieves instantaneous wide-area imaging through the development and deployment of phased-array feed systems on parabolic reflectors. The large field-of-view makes ASKAP an unprecedented synoptic telescope that will make substantial advances in SKA key science. ASKAP will be located at the Murchison Radio Observatory in inland Western Australia, one of the most radio-quiet locations on the Earth and one of two sites selected by the international community as a potential location for the SKA. In this paper, we outline an ambitious science program for ASKAP, examining key science such as understanding the evolution, formation and population of galaxies including our own, understanding the magnetic Universe, revealing the transient radio sky and searching for gravitational waves.