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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.
Sulfur-bearing monazite-(Ce) occurs in silicified carbonatite at Eureka, Namibia, forming rims up to ~0.5 mm thick on earlier-formed monazite-(Ce) megacrysts. We present X-ray photoelectron spectroscopy data demonstrating that sulfur is accommodated predominantly in monazite-(Ce) as sulfate, via a clino-anhydrite-type coupled substitution mechanism. Minor sulfide and sulfite peaks in the X-ray photoelectron spectra, however, also indicate that more complex substitution mechanisms incorporating S2– and S4+ are possible. Incorporation of S6+ through clino-anhydrite-type substitution results in an excess of M2+ cations, which previous workers have suggested is accommodated by auxiliary substitution of OH– for O2–. However, Raman data show no indication of OH–, and instead we suggest charge imbalance is accommodated through F– substituting for O2–. The accommodation of S in the monazite-(Ce) results in considerable structural distortion that may account for relatively high contents of ions with radii beyond those normally found in monazite-(Ce), such as the heavy rare earth elements, Mo, Zr and V. In contrast to S-bearing monazite-(Ce) in other carbonatites, S-bearing monazite-(Ce) at Eureka formed via a dissolution–precipitation mechanism during prolonged weathering, with S derived from an aeolian source. While large S-bearing monazite-(Ce) grains are likely to be rare in the geological record, formation of secondary S-bearing monazite-(Ce) in these conditions may be a feasible mineral for dating palaeo-weathering horizons.
Flanged ventricular catheters are now used infrequently. Many patients with longstanding hydrocephalus still harbor these catheters, either as their current ventricular catheter, or as a retained catheter from a prior implant. The removal of flanged ventricular catheters is sometimes necessary, and may be challenging due to intraventricular adhesions. We describe the use of an endoscopic technique for the successful retrieval of flanged ventricular catheters in two patients. The technique described in this report may be helpful for patients that have flanged ventricular catheters that must be removed.
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.
The anabolic potential of a dietary protein is determined by its ability to elicit postprandial rises in circulating essential amino acids and insulin. Minimal data exist regarding the bioavailability and insulinotropic effects of non-animal-derived protein sources. Mycoprotein is a sustainable and rich source of non-animal-derived dietary protein. We investigated the impact of mycoprotein ingestion, in a dose–response manner, on acute postprandial hyperaminoacidaemia and hyperinsulinaemia. In all, twelve healthy young men completed five experimental trials in a randomised, single-blind, cross-over design. During each trial, volunteers consumed a test drink containing either 20 g milk protein (MLK20) or a mass matched (not protein matched due to the fibre content) bolus of mycoprotein (20 g; MYC20), a protein matched bolus of mycoprotein (40 g; MYC40), 60 g (MYC60) or 80 g (MYC80) mycoprotein. Circulating amino acid, insulin and uric acid concentrations, and clinical chemistry profiles, were assessed in arterialised venous blood samples during a 4-h postprandial period. Mycoprotein ingestion resulted in slower but more sustained hyperinsulinaemia and hyperaminoacidaemia compared with milk when protein matched, with overall bioavailability equivalent between conditions (P>0·05). Increasing the dose of mycoprotein amplified these effects, with some evidence of a plateau at 60–80 g. Peak postprandial leucine concentrations were 201 (sem 24) (30 min), 118 (sem 10) (90 min), 150 (sem 14) (90 min), 173 (sem 23) (45 min) and 201 (sem 21 (90 min) µmol/l for MLK20, MYC20, MYC40, MYC60 and MYC80, respectively. Mycoprotein represents a bioavailable and insulinotropic dietary protein source. Consequently, mycoprotein may be a useful source of dietary protein to stimulate muscle protein synthesis rates.
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).
Background: Patients who require hospitalization for a mild or moderate traumatic brain injury (TBI) are often discharged home with uncertainty around their full recovery. This study examines the frequency and severity of common post-TBI symptoms, as assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPCQ). Methods: All adult TBI inpatients discharged home from the Neurosurgery service were interviewed by phone at two weeks by a rehab-based nurse practitioner. RPCQ components (cognitive, emotional, and somatic) were analyzed; findings and management recommendations were communicated to family practitioners and the treating neurosurgeon. Results: In 46 patients, cognitive symptoms were present in 52%, 91% had somatic, and 100% had emotional symptoms. Fatigue was the most common symptom (67%). Double vision was the least common symptom (4%). Recommendations for managing symptoms, return to work, and need for formal clinical assessment were provided for 37% of cases. Conclusions: All patients admitted to neurosurgery with mild or moderate TBI had symptoms at two weeks. The RPCQ is a low-cost structured evaluative tool which highlights needs and provides guidance for patients and care-givers; it also seems effective in identifying those who may require formal clinical assessment.
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.
Climate change is a growing international concern, and it is well established that the release of greenhouse gases (GHG) is a contributing factor. So far, within animal production, there is little or no concerted effort on long-term breeding strategies to mitigate against GHG from ruminants. In recent years, several consortia have been formed to collect and combine data for genetic evaluation. The discussion areas of these consortia focus on (1) What are methane-determining factors, (2) What are genetic parameters for methane emissions, (3) What proxies can be used, and what is their association with methane emission, and (4) How to move on with breeding for lower emitting animals? The methane-determining factors can be divided into four groups: (1) rumen microbial population, (2) feed intake and diet composition, (3) host physiology and (4) host genetics. The genetic parameters show that enteric methane is a heritable trait, and that it is highly genetically correlated with dry matter intake. So far, the most useful proxies relate to feed intake, milk mid IR spectral data and fatty acids in the milk. To be able to move on with a genetic evaluation and ranking of animals for methane emission, it is crucial to make measurements on commercial farms. In order to make that possible, it will be necessary to develop phenotypes that can be used by the farmer to optimise the production on farm level. Also, it is crucial to develop equipment that makes it possible to make measurements without interfering with everyday routines or identify proxies that are highly related to methane and which could easily be measured on a large scale. International collaboration is essential to make progress in this area. This is both in terms of sharing ideas, experiences and phenotypes, but also in terms of coming to a consensus regarding what phenotype to collect and to select for.
The number needed to treat (NNT) statistic was developed to facilitate the
practice of evidence-based medicine. Placebo was assumed to be
therapeutically inert when the NNT was originally conceived, but more recent
data for conditions such as major depressive disorder (MDD) suggest that the
placebo control condition can have considerable therapeutic effects.
Complications arise because the NNT calculated from randomised controlled
trials (RCTs) reflects a comparison between medication plus clinical
management and placebo plus clinical management, whereas, in the clinical
setting, physicians choose between prescribing open medication, observing a
patient over time with a supportive approach, and doing nothing. Thus, NNTs
derived from clinical trials are not directly relevant to clinical
decision-making, because they are based on control conditions that do not
exist in standard practice. Additional difficulties may arise when using
NNTs to compare alternative treatments for MDD, such as medication and
psychotherapy, since these comparisons require the control conditions upon
which the respective NNTs are based to be similar. Whereas pill placebo
conditions include intensive clinical management and elicit expectations of
improvement, attention control conditions for psychotherapy research are
less well developed. Often the effects of psychotherapy are gauged against a
wait-list control condition, which has substantially fewer therapeutic
components than a pill placebo control condition. To improve the clinical
utility of NNTs for the treatment of MDD, we advocate effectiveness studies
that include treatment conditions resembling actual clinical practice,
rather than using placebo-controlled RCTs for this purpose. Until such
studies are performed, the effect of bias in comparing NNTs across
treatments can be controlled by ensuring that the RCT control conditions
upon which the NNTs are based are comparable.
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.