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We used British national survey data to test specific hypotheses that mood instability 1) is associated with psychosis and individual psychotic phenomena, 2) predicts the later emergence of auditory hallucinations and paranoid ideation, and 3) mediates the link between child sexual abuse and psychosis.
We analysed data from the 2000 and 2007 UK national surveys of psychiatric morbidity (N=8580 and 7403 respectively). The 2000 survey included an 18-month follow-up of a subsample (N=2406). Mood instability was assessed from the Structured Clinical Interview for DSMIV Axis II (SCID-II) questionnaire. Our dependent variables comprised auditory hallucinations, paranoid ideation, the presence of psychosis overall, and a 15-item paranoia scale
Mood Instability was strongly associated in cross-sectional analyses with psychosis (2000 OR: 7.5; 95% CI: I 4.1–13.8; 2007: OR 21.4; CI 9.7–41.2), paranoid ideation (2000: OR: 4.7; CI 4.1–5.4; 2007: OR 5.7; CI 4.9–6.7), auditory hallucinations (2000: OR: 3.4; CI 2.6–4.4; 2007: OR 3.5; CI 2.7–4.7) and paranoia total score (2000: Coefficient: 3.6;CI 3.3–3.9), remaining so after adjustment for current mood state. Baseline mood instability significantly predicted 18-month inceptions of paranoid ideation (OR: 2.3;CI 1.6–3.3) and of auditory hallucinations (OR: 2.6;CI 1.5–4.4). Finally it mediated a third of the total association of child sexual abuse with psychosis and persecutory ideation, and a quarter of that with auditory hallucinations.
Mood instability is a prominent feature of psychotic experience, and may have a role in its genesis. Targeting mood instability could lead to innovative treatments for psychosis.
Sexual dysfunction occurs in 40%-60% of patients with major depressive disorder (MDD), due to either the illness itself and/or the effects of antidepressant treatment. The phase-2 CLARITY trial recently demonstrated the efficacy of adjunctive pimavanserin (PIM) for MDD when added to ongoing selective serotonin or serotonin–norepinephrine reuptake inhibitor (SSRI/SNRI) treatment. No new safety observations were reported in this study. This post-hoc analysis examines the potential impact of PIM treatment on sexual function.
Study methodology has been presented previously (APA 2019). Adult male and female patients with moderate-to-severe MDD were randomized to PIM 34 mg/day (n=51) or placebo (PBO, n=152) added to ongoing SSRI/SNRI treatment. Massachusetts General Hospital–Sexual Functioning Inventory (MGH-SFI) and Hamilton Depression Rating Scale, 17-item version (HAMD-17) item 14 (sexual interest) scores were examined by analysis of covariance.
Adjunctive PIM resulted in significantly greater 5-week reduction (improvement) relative to SSRI/SNRI treatment plus placebo on mean MGH-SFI scores (difference –0.634, SE 0.167; P<0.001; effect size [ES], Cohen’s d 0.614). Similarly, PIM resulted in greater improvement compared with placebo on individual MGH-SFI items that applied to both males and females: Interest in Sex (P=0.006; ES=0.483), Ability to Get Sexually Aroused/Excited (P=0.001; ES=0.560), Ability to Achieve Orgasm (P<0.001; ES=0.609), Overall Sexual Satisfaction (P=0.003; ES=0.524). HAMD-17 item 14 scores were also significantly more reduced (improved) with PIM (P<0.001; ES=0.574).
These results underscore the potential of adjunctive PIM for improving sexual function in patients with MDD and inadequate response to SSRIs/SNRIs. Potential benefits should be confirmed in further studies.
Depression is the leading cause of disability worldwide, with fewer than 50% of treated patients achieving full remission. This study (“CLARITY,” ACP-103-042: NCT03018340) examined the 5-HT2A inverse agonist pimavanserin (PIM) as a potential adjunctive treatment for major depressive disorder (MDD).
Adult female and male subjects with a DSM-5 primary diagnosis of a major depressive episode as part of MDD, inadequate response to ongoing SSRIs or SNRIs of adequate dose and duration as confirmed by the Massachusetts General Hospital Antidepressant Treatment History Questionnaire, and a MADRS total score >20 were randomized to PIM 34 mg/day or placebo (PBO) added to their SSRI/SNRI treatment. A sequential parallel comparison design was used, consisting of two 5-week stages. PBO nonresponders in Stage-1 who met prespecified criteria were re-randomized to PIM or PBO for the second period (Stage-2). The primary efficacy measure was the weighted average of Stage-1 and Stage-2 total scores of the HAMD-17.
Of the 207 patients enrolled, 52 received PIM, and 155 received PBO in Stage 1. Mean age was 46.2 years, and 72.9% of patients were female. Baseline MADRS total (mean [SD]: 31.5 [0.4]) and HAMD-17 total scores (22.2 [0.3]) indicated a moderate overall severity of illness. PIM met the primary endpoint, reducing the weighted Stage-1/Stage-2 HAMD-17 total score relative to PBO (least-square means [LSM] difference, –1.7; standard error [SE], 0.9; P=0.04). Stage-1 PIM patients demonstrated highly significant 5-week improvement on the HAMD-17 (LSM difference=–4.0, SE=1.1; P<0.001; effect size, Cohen’s d: 0.626), separating from placebo by the end of Week 1 (LSM difference=–1.7, SE=0.8; P=0.04). Stage-2 results showed no significant separation among Stage-1 placebo nonresponders (P=0.69). In Stage 2, a substantively smaller number of subjects (n=58) were rerandomized than planned, likely due to restrictive criteria for re-randomization. Greater overall improvement was seen with PIM relative to PBO on the key secondary endpoint, the Sheehan Disability Scale (LSM difference=–0.8, SE=0.3; P=0.004), and positive results were also seen on 7 of the 11 other secondary endpoints, including responder rate (≥50% reduction in HAMD-17 total; P=0.007), Massachusetts General Hospital Sexual Functioning Index (P<0.001), and Karolinska Sleepiness Scale for daytime sleepiness (P=0.02). Discontinuations due to adverse events were low (PIM 1.2%, PBO 3.2%). One serious adverse event was reported in each treatment group, deemed unrelated to treatment. No deaths were reported. Laboratory assessments, electrocardiography, and changes in vital signs were unremarkable, and no new safety signals were reported.
Study data provide evidence of the efficacy, safety, and tolerability of adjunctive PIM in treating MDD inadequately responsive to SSRI or SNRI therapy. Efforts to confirm these results are ongoing in a Phase 3 program.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
Executive functions (EF) drive health and educational outcomes and therefore are increasingly common treatment targets. Most treatment trials rely on questionnaires to capture meaningful change because ecologically valid, pediatric performance-based EF tasks are lacking. The Executive Function Challenge Task (EFCT) is a standardized, treatment-sensitive, objective measure which assesses flexibility and planning in the context of provocative social interactions, making it a “hot” EF task.
We investigate the structure, reliability, and validity of the EFCT in youth with autism (Autism Spectrum Disorder; n = 129), or attention deficit hyperactivity disorder with flexibility problems (n = 93), and typically developing (TD; n = 52) youth.
The EFCT can be coded reliably, has a two-factor structure (flexibility and planning), and adequate internal consistency and consistency across forms. Unlike a traditional performance-based EF task (verbal fluency), it shows significant correlations with parent-reported EF, indicating ecological validity. EFCT performance distinguishes youth with known EF problems from TD youth and is not significantly related to visual pattern recognition, or social communication/understanding in autistic children.
The EFCT demonstrates adequate reliability and validity and may provide developmentally appropriate, treatment-sensitive, and ecologically valid assessment of “hot” EF in youth. It can be administered in controlled settings by masked administrators.
The diurnal feeding patterns of dairy cows affects the 24 h robot utilisation of pasture-based automatic milking systems (AMS). A decline in robot utilisation between 2400 and 0600 h currently occurs in pasture-based AMS, as cow feeding activity is greatly reduced during this time. Here, we investigate the effect of a temporal variation in feed quality and quantity on cow feeding behaviour between 2400 and 0600 h as a potential tool to increase voluntary cow trafficking in an AMS at night. The day was allocated into four equal feeding periods (0600 to 1200, 1200 to 1800, 1800 to 2400 and 2400 to 0600 h). Lucerne hay cubes (CP = 19.1%, water soluble carbohydrate = 3.8%) and oat, ryegrass and clover hay cubes with 20% molasses (CP = 11.8%, water soluble carbohydrate = 10.7%) were offered as the ‘standard’ and ‘preferred’ (preference determined previously) feed types, respectively. The four treatments were (1) standard feed offered ad libitum (AL) throughout 24 h; (2) as per AL, with preferred feed replacing standard feed between 2400 and 0600 h (AL + P); (3) standard feed offered at a restricted rate, with quantity varying between each feeding period (20:10:30:60%, respectively) as a proportion of the (previously) measured daily ad libitum intake (VA); (4) as per VA, with preferred feed replacing standard feed between 2400 and 0600 h (VA + P). Eight non-lactating dairy cows were used in a 4 × 4 Latin square design. During each experimental period, treatment cows were fed for 7 days, including 3 days habituation and 4 days data collection. Total daily intake was approximately 8% greater (P < 0.001) for the AL and AL + P treatments (23.1 and 22.9 kg DM/cow) as compared with the VA and VA + P treatments (21.6 and 20.9 kg DM/cow). The AL + P and VA treatments had 21% and 90% greater (P < 0.001) dry matter intake (DMI) between 2400 and 0600 h, respectively, compared with the AL treatment. In contrast, the VA + P treatment had similar DMI to the VA treatment. Our experiment shows ability to increase cow feeding activity at night by varying feed type and quantity, though it is possible that a penalty to total DMI may occur using VA. Further research is required to determine if the implementation of variable feed allocation on pasture-based AMS farms is likely to improve milking robot utilisation by increasing cow feeding activity at night.
Sprays are a class of multiphase flows which exhibit a wide range of drop size and velocity scales spanning several orders of magnitude. The objective of the current work is to experimentally investigate the prospect of dynamical similarity in these flows. We are also motivated to identify a choice of length and time scales which could lead towards a universal description of the drop size and velocity spectra. Towards this end, we have fabricated a cohort of geometrically similar pressure swirl atomizers using micro-electromechanical systems (MEMS) as well as additive manufacturing technology. We have characterized the dynamical characteristics of the sprays as well as the drop size and velocity spectra (in terms of probability density functions, p.d.f.s) over a wide range of Reynolds (
) and Weber numbers (
) using high-speed imaging and phase Doppler interferometry, respectively. We show that the dimensionless Sauter mean diameter (
) scaled to the boundary layer thickness in the liquid sheet at the nozzle exit (
) exhibits self-similarity in the core region of the spray, but not in the outer zone. In addition, we show that global drop size spectra in the sprays show two distinct characteristics. The spectra from varying
collapse onto a universal p.d.f. for drops of size
, a residual effect of
persists in the size spectra. We explain this characteristic by the fact that the physical mechanisms that cause large drops is different from that which is responsible for the small drops. Similarly, with the liquid sheet velocity at the nozzle exit (
) as the choice of velocity scale, we show that drops moving with a velocity
collapse onto a universal p.d.f., while drops with
exhibit a residual effect of
. From these observations, we suggest that physically accurate models for drop size and velocity spectra should rely on piecewise descriptions of the p.d.f. rather than invoking a single mathematical form for the entire distribution. Finally, we show from a dynamical modal analysis that the conical liquid sheet flapping characteristics exhibit a sharp transition in Strouhal number (
) at a critical
Achieving a consistent level of robot utilisation throughout 24 h maximises automatic milking system (AMS) utilisation. However, levels of robot utilisation in the early morning hours are typically low, caused by the diurnal feeding behaviour of cows, limiting the inherent capacity and total production of pasture-based AMS. Our objective was to determine robot utilisation throughout 24 h by dairy cows, based on milking frequency (MF; milking events per animal per day) in a pasture-based AMS. Milking data were collected from January and February 2013 across 56 days, from a single herd of 186 animals (Bos taurus) utilising three Lely A3 robotic milking units, located in Tasmania, Australia. The dairy herd was categorised into three equal sized groups (n=62 per group) according to the cow’s mean daily MF over the duration of the study. Robot utilisation was characterised by an interaction (P< 0.001) between the three MF groups and time of day, with peak milking time for high MF cows within one h of a fresh pasture allocation becoming available, followed by the medium MF and low MF cows 2 and 4 h later, respectively. Cows in the high MF group also presented for milking between 2400 and 0600 h more frequently (77% of nights), compared to the medium MF group (57%) and low MF group (50%). This study has shown the formation of three distinct groups of cows within a herd, based on their MF levels. Further work is required to determine if this finding is replicated across other pasture-based AMS farms.
What Australian psychologists currently learn about specific learning disorders (SLDs) through postgraduate-level training is not clear. Accordingly, the current Australia-wide study analysed 800 postgraduate psychology unit handbook entries to identify which courses teach about SLD and what they teach in this area. Only 2.38% of the identified units explicitly indicated SLD-related content, with 0.38% solely dedicated to SLD content. Descriptive analyses revealed differences in labels used for SLD. Thematic analyses identified five areas of knowledge and skills across SLD units including assessment, intervention, theory and empirical evidence, developmental and cultural awareness and sensitivity, and interpersonal communication. The present findings can inform future refinements to university-level psychology programs across Australia by highlighting the gaps and needs in psychology training.
Non-psychotic affective symptoms are important components of psychotic syndromes. They are frequent and are now thought to influence the emergence of paranoia and hallucinations. Evidence supporting this model of psychosis comes from recent cross-fertilising epidemiological and intervention studies. Epidemiological studies identify plausible targets for intervention but must be interpreted cautiously. Nevertheless, causal inference can be strengthened substantially using modern statistical methods.
Directed Acyclic Graphs were used in a dynamic Bayesian network approach to learn the overall dependence structure of chosen variables. DAG-based inference identifies the most likely directional links between multiple variables, thereby locating them in a putative causal cascade. We used initial and 18-month follow-up data from the 2000 British National Psychiatric Morbidity survey (N = 8580 and N = 2406).
We analysed persecutory ideation, hallucinations, a range of affective symptoms and the effects of cannabis and problematic alcohol use. Worry was central to the links between symptoms, with plausible direct effects on insomnia, depressed mood and generalised anxiety, and recent cannabis use. Worry linked the other affective phenomena with paranoia. Hallucinations were connected only to worry and persecutory ideation. General anxiety, worry, sleep problems, and persecutory ideation were strongly self-predicting. Worry and persecutory ideation were connected over the 18-month interval in an apparent feedback loop.
These results have implications for understanding dynamic processes in psychosis and for targeting psychological interventions. The reciprocal influence of worry and paranoia implies that treating either symptom is likely to ameliorate the other.
Textual data are plagued by underreporting bias. For example, news sources often fail to report human rights violations. Cook et al. propose a multi-source estimator to gauge, and to account for, the underreporting of state repression events within human codings of news texts produced by the Agence France-Presse and Associated Press. We evaluate this estimator with Monte Carlo experiments, and then use it to compare the prevalence and seriousness of underreporting when comparable texts are machine coded and recorded in the World-Integrated Crisis Early Warning System dataset. We replicate Cook et al.’s investigation of human-coded state repression events with our machine-coded events, and validate both models against an external measure of human rights protections in Africa. We then use the Cook et al. estimator to gauge the seriousness and prevalence of underreporting in machine and human-coded event data on human rights violations in Colombia. We find in both applications that machine-coded data are as valid as human-coded data.
In recent decades, instructors have increasingly adopted the use of “serious” games in their classrooms. Typically, these games take the form of role-playing simulations or wargames. However, online computer-run games have opened up new possibilities: to explore complex conceptual relationships, to utilize and display asymmetric information, to be playable anywhere and by anyone, and more. This article describes the game, Dark Networks, and shows why this type of game is valuable as well as how it has been used for pedagogical gains.
The age-metallicity relation (AMR) is a fundamental observational constraint for understanding how the Galactic disc formed and evolved chemically in time. However, there is not yet an agreement on the observational properties of the AMR, primarily due to the difficulty in obtaining accurate ages for individual field stars. We have started an observational campaign for providing new observational input by using wide white dwarf-main sequence (WDMS) binaries. WDs are natural clocks and can be used to derive accurate ages. Metallicities can be obtained from the MS companions. Since the progenitors of WDs and the MS stars were born at the same time, WDMS provide a unique opportunity to constrain in a robust way the properties of the AMR. We present the AMR derived from analysing a pilot sample of 23 WDMS and provide clear evidence for the lack of correlation between age and metallicity at young and intermediate ages.
We use the Sloan Digital Sky Survey Data Release 12, which is the largest available white dwarf catalog to date, to study the evolution of the kinematical properties of the population of white dwarfs in the Galactic disc. We derive masses, ages, photometric distances and radial velocities for all white dwarfs with hydrogen-rich atmospheres. For those stars for which proper motions from the USNO-B1 catalog are available the true three-dimensional components of the stellar space velocity are obtained. This subset of the original sample comprises 20,247 objects, making it the largest sample of white dwarfs with measured three-dimensional velocities. Furthermore, the volume probed by our sample is large, allowing us to obtain relevant kinematical information. In particular, our sample extends from a Galactocentric radial distance RG = 7.8 kpc to 9.3 kpc, and vertical distances from the Galactic plane ranging from Z = −0.5 kpc to 0.5 kpc. We examine the mean components of the stellar three-dimensional velocities, as well as their dispersions with respect to the Galactocentric and vertical distances. We confirm the existence of a mean Galactocentric radial velocity gradient, ∂〈VR〉/∂RG = −3 ± 5 km s−1 kpc−1. We also confirm North-South differences in 〈Vz〉. Specifically, we find that white dwarfs with Z > 0 (in the North Galactic hemisphere) have 〈Vz〉 < 0, while the reverse is true for white dwarfs with Z < 0. The age-velocity dispersion relation derived from the present sample indicates that the Galactic population of white dwarfs may have experienced an additional source of heating, which adds to the secular evolution of the Galactic disc.
This paper presents the first major data release and survey description for the ANU WiFeS SuperNovA Programme. ANU WiFeS SuperNovA Programme is an ongoing supernova spectroscopy campaign utilising the Wide Field Spectrograph on the Australian National University 2.3-m telescope. The first and primary data release of this programme (AWSNAP-DR1) releases 357 spectra of 175 unique objects collected over 82 equivalent full nights of observing from 2012 July to 2015 August. These spectra have been made publicly available via the WISEREP supernova spectroscopy repository.
We analyse the ANU WiFeS SuperNovA Programme sample of Type Ia supernova spectra, including measurements of narrow sodium absorption features afforded by the high spectral resolution of the Wide Field Spectrograph instrument. In some cases, we were able to use the integral-field nature of the Wide Field Spectrograph instrument to measure the rotation velocity of the SN host galaxy near the SN location in order to obtain precision sodium absorption velocities. We also present an extensive time series of SN 2012dn, including a near-nebular spectrum which both confirms its ‘super-Chandrasekhar’ status and enables measurement of the sub-solar host metallicity at the SN site.
Cannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity.
We tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test, a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory. Dopamine synthesis capacity, indexed as the influx rate constant Kicer, was measured in 10 users and six controls with 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine positron emission tomography.
There was no significant difference in aberrant salience between the groups [F1,32 = 1.12, p = 0.30 (implicit); F1,32 = 1.09, p = 0.30 (explicit)]. Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r = 0.61, p = 0.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F1,15 = 5.8, p = 0.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r = −0.91, p = 0.01), whereas this relationship was non-significant within users (difference between correlations: Z = −2.05, p = 0.04).
Aberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use.
Toxigenic strains of Vibrio cholerae serogroups O1 and O139 have caused cholera epidemics, but other serogroups – such as O75 or O141 – can also produce cholera toxin and cause severe watery diarrhoea similar to cholera. We describe 31 years of surveillance for toxigenic non-O1, non-O139 infections in the United States and map these infections to the state where the exposure probably originated. While serogroups O75 and O141 are closely related pathogens, they differ in how and where they infect people. Oysters were the main vehicle for O75 infection. The vehicles for O141 infection include oysters, clams, and freshwater in lakes and rivers. The patients infected with serogroup O75 who had food traceback information available ate raw oysters from Florida. Patients infected with O141 ate oysters from Florida and clams from New Jersey, and those who only reported being exposed to freshwater were exposed in Arizona, Michigan, Missouri, and Texas. Improving the safety of oysters, specifically, should help prevent future illnesses from these toxigenic strains and similar pathogenic Vibrio species. Post-harvest processing of raw oysters, such as individual quick freezing, heat-cool pasteurization, and high hydrostatic pressurization, should be considered.
Several extragalactic HI surveys using a λ21 cm 13-beam focal plane array will begin in early 1997 using the Parkes 64 m telescope. These surveys are designed to detect efficiently nearby galaxies that have failed to be identified optically because of low optical surface brightness or high optical extinction. We discuss scientific and technical aspects of the multibeam receiver, including astronomical objectives, feed, receiver and correlator design and data acquisition. A comparison with other telescopes shows that the Parkes multibeam receiver has significant speed advantages for any large-area λ21 cm galaxy survey in the velocity range range 0–14000 km s−1.
During 1990 we surveyed the southern sky using a multi-beam receiver at frequencies of 4850 and 843 MHz. The half-power beamwidths were 4 and 25 arcmin respectively. The finished surveys cover the declination range between +10 and −90 degrees declination, essentially complete in right ascension, an area of 7.30 steradians. Preliminary analysis of the 4850 MHz data indicates that we will achieve a five sigma flux density limit of about 30 mJy. We estimate that we will find between 80 000 and 90 000 new sources above this limit. This is a revised version of the paper presented at the Regional Meeting by the first four authors; the surveys now have been completed.