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Evaluate the time-course, severity and resolution patterns of adverse events (AEs) occurring with long-term aripiprazole treatment for irritability associated with autistic disorder.
Participants were treated with aripiprazole in a 52-week, open-label, flexibly dosed (2–15 mg/day) study. Subjects had either completed one of two 8-week randomised trials or were de novo. AEs with an incidence of ≥10% were evaluated by incidence, peak first onset, severity, percent resolved and time to resolution.
A total of 330 subjects entered open-label treatment; 199 completed 52 weeks. Mean dose for the population stabilised at around 10 mg/day after approximately 4 months. Thirteen AEs had an incidence of ≥10%; most were mild or moderate in severity. Vomiting, diarrhoea and headache had an early first onset and tended to resolve fairly quickly.
Sedation, fatigue and insomnia also appeared early and resolved in a majority of cases, but not as quickly. Increased appetite appeared early (followed by increased weight) and fewer weight-related AEs resolved. More than half of the subjects increased their weight by at least one percentile category rank; nevertheless, only a small proportion of subjects with normal baseline metabolic or glucose measures had a treatment-emergent, clinically relevant laboratory abnormality. Nasopharyngitis, upper respiratory infection, cough, nasal congestion and pyrexia all had peak onset at variable times during the study, resolving in nearly all cases, with short time to resolution.
AEs were mostly mild or moderate and of variable duration. Increased weight was observed.
Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
We investigate the interstellar medium towards seven TeV gamma-ray sources thought to be pulsar wind nebulae using Mopra molecular line observations at 7 mm [CS(1–0), SiO(1–0, v = 0)], Nanten CO(1–0) data and the Southern Galactic Plane Survey/GASS Hi survey. We have discovered several dense molecular clouds co-located to these TeV gamma-ray sources, which allows us to search for cosmic rays coming from progenitor SNRs or, potentially, from pulsar wind nebulae. We notably found SiO(1–0, v = 0) emission towards HESS J1809–193, highlighting possible interaction between the adjacent supernova remnant SNR G011.0–0.0 and the molecular cloud at d ∼ 3.7 kpc. Using morphological features, and comparative studies of our column densities with those obtained from X-ray measurements, we claim a distance d ∼ 8.6 − 9.7kpc for SNR G292.2–00.5, d ∼ 3.5 − 5.6 kpc for PSR J1418–6058 and d ∼ 1.5 kpc for the new SNR candidate found towards HESS J1303–631. From our mass and density estimates of selected molecular clouds, we discuss signatures of hadronic/leptonic components from pulsar wind nebulae and their progenitor SNRs. Interestingly, the molecular gas, which overlaps HESS J1026–582 at d ∼ 5 kpc, may support a hadronic origin. We find however that this scenario requires an undetected cosmic-ray accelerator to be located at d < 10 pc from the molecular cloud. For HESS J1809–193, the cosmic rays which have escaped SNR G011.0–0.0 could contribute to the TeV gamma-ray emission. Finally, from the hypothesis that at most 20% the pulsar spin down power could be converted into CRs, we find that among the studied pulsar wind nebulae, only those from PSR J1809–1917 could potentially contribute to the TeV emission.
We present observations of 50 deg2 of the Mopra carbon monoxide (CO) survey of the Southern Galactic Plane, covering Galactic longitudes l = 300–350° and latitudes |b| ⩽ 0.5°. These data have been taken at 0.6 arcmin spatial resolution and 0.1 km s−1spectral resolution, providing an unprecedented view of the molecular clouds and gas of the Southern Galactic Plane in the 109–115 GHz J = 1–0 transitions of 12CO, 13CO, C18O, and C17O.
We present a series of velocity-integrated maps, spectra, and position-velocity plots that illustrate Galactic arm structures and trace masses on the order of ~106 M⊙ deg−2, and include a preliminary catalogue of C18O clumps located between l = 330–340°. Together with the information about the noise statistics of the survey, these data can be retrieved from the Mopra CO website and the PASA data store.
Mechanical Turk has become an important source of subjects for social science experiments, providing a low-cost alternative to the convenience of using undergraduates while avoiding the expense of drawing fully representative samples. However, we know little about how the rates we pay to “Turkers” for participating in social science experiments affects their participation. This study examines subject performance using two experiments – a short survey experiment and a longer dynamic process tracing study of political campaigns – that recruited Turkers at different rates of pay. Looking at demographics and using measures of attention, engagement and evaluation of the candidates, we find no effects of pay rates upon subject recruitment or participation. We conclude by discussing implications and ethical standards of pay.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
The present study addresses the reaction zone structure and burning mechanism of unstable detonations. Experiments investigated mainly two-dimensional methane–oxygen cellular detonations in a thin channel geometry. The sufficiently high temporal resolution permitted the determination of the probability density function of the shock distribution, a power law with an exponent of
, and the burning rate of unreacted pockets from their edges – through surface turbulent flames with a speed approximately 3–7 times larger than the laminar one at the local conditions. Numerical simulations were performed using a novel large-eddy simulation method where the reactions due to both autoignition and turbulent transport were treated exactly at the subgrid scale in a reaction–diffusion formulation. The model is an extension of Kerstein and Menon’s linear eddy model for large-eddy simulation to treat flows with shock waves and rapid gas-dynamic transients. The two-dimensional simulations recovered well the amplification of the laminar flame speed due to the turbulence generated mainly by the shear layers originating from the triple points and subsequent Richtmyer–Meshkov instability associated with the internal pressure waves. The simulations clarified how the level of turbulence generated controlled the burning rate of the pockets, the hydrodynamic thickness of the wave, the cellular structure and its distribution. Three-dimensional simulations were found to be in general good agreement with the two-dimensional ones, in that the subgrid-scale model captured the ensuing turbulent burning once the scales associated with the cellular dynamics, where turbulent kinetic energy is injected, are well resolved.
Pertussis epidemics have displayed substantial spatial heterogeneity in countries with high socioeconomic conditions and high vaccine coverage. This study aims to investigate the relationship between pertussis risk and socio-environmental factors on the spatio-temporal variation underlying pertussis infection. We obtained daily case numbers of pertussis notifications from Queensland Health, Australia by postal area, for the period January 2006 to December 2012. A Bayesian spatio-temporal model was used to quantify the relationship between monthly pertussis incidence and socio-environmental factors. The socio-environmental factors included monthly mean minimum temperature (MIT), monthly mean vapour pressure (VAP), Queensland school calendar pattern (SCP), and socioeconomic index for area (SEIFA). An increase in pertussis incidence was observed from 2006 to 2010 and a slight decrease from 2011 to 2012. Spatial analyses showed pertussis incidence across Queensland postal area to be low and more spatially homogeneous during 2006–2008; incidence was higher and more spatially heterogeneous after 2009. The results also showed that the average decrease in monthly pertussis incidence was 3·1% [95% credible interval (CrI) 1·3–4·8] for each 1 °C increase in monthly MIT, while average increase in monthly pertussis incidences were 6·2% (95% CrI 0·4–12·4) and 2% (95% CrI 1–3) for SCP periods and for each 10-unit increase in SEIFA, respectively. This study demonstrated that pertussis transmission is significantly associated with MIT, SEIFA, and SCP. Mapping derived from this work highlights the potential for future investigation and areas for focusing future control strategies.
Expert judgement is frequently used within general insurance. It tends to be a method of last resort and used where data is sparse, non-existent or non-applicable to the problem under consideration. Whilst such judgements can significantly influence the end results, their quality is highly variable. The use of the term “expert judgement” itself can lend a generous impression of credibility to what may be a little more than a guess. Despite the increased emphasis placed on the importance of robust expert judgements in regulation, actuarial research to date has focussed on the more technical or data-driven methods, with less emphasis on how to use and incorporate softer information or how best to elicit judgements from others in a way that reduces cognitive biases. This paper highlights the research that the Getting Better Judgement Working Party has conducted in this area. Specifically, it covers the variable quality of expert judgement, both within and outside the regulatory context, and presents methods that may be applied to improve its formation. The aim of this paper is to arm the insurance practitioner with tools to distinguish between low-quality and high-quality judgements and improve the robustness of judgements accordingly, particularly for highly material circumstances.
Fronto-limbic structural brain abnormalities have been reported in patients with bipolar disorder (BD), but findings in individuals at increased genetic risk of developing BD have been inconsistent. We conducted a study in adolescents and young adults (12–30 years) comparing measures of fronto-limbic cortical and subcortical brain structure between individuals at increased familial risk of BD (at risk; AR), subjects with BD and controls (CON). We separately examined cortical volume, thickness and surface area as these have distinct neurodevelopmental origins and thus may reflect differential effects of genetic risk.
We compared fronto-limbic measures of grey and white matter volume, cortical thickness and surface area in 72 unaffected-risk individuals with at least one first-degree relative with bipolar disorder (AR), 38 BD subjects and 72 participants with no family history of mental illness (CON).
The AR group had significantly reduced cortical thickness in the left pars orbitalis of the inferior frontal gyrus (IFG) compared with the CON group, and significantly increased left parahippocampal gyral volume compared with those with BD.
The finding of reduced cortical thickness of the left pars orbitalis in AR subjects is consistent with other evidence supporting the IFG as a key region associated with genetic liability for BD. The greater volume of the left parahippocampal gyrus in those at high risk is in line with some prior reports of regional increases in grey matter volume in at-risk subjects. Assessing multiple complementary morphometric measures may assist in the better understanding of abnormal developmental processes in BD.
Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives.
Neurocognitive and social cognitive ability was examined in 99 young people (age range 16–30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD.
Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs.
Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.
Under intensive pig husbandry, outdoor systems offer a more complex physical and social environment compared with indoor systems (farrowing sheds). As the rearing environment affects behavioural development, it can, therefore, influence behavioural responses of pigs to stressful environments in later stages of production. We tested how the rearing environment influenced behavioural responses to a novel arena test in piglets on the day that they were weaned and mixed into large groups. We recorded video footage and compared the behavioural responses of 30 outdoor-raised and 30 farrowing shed-raised piglets tested in an experimental arena and sequentially exposed to four challenges (each for 5 min) on the day of weaning. Quantitative and qualitative behavioural measures were recorded using time budgets and scoring demeanour or ‘qualitative behavioural expression’ (using Qualitative Behavioural Assessment (QBA)). When held in isolation (challenge 1), both groups were scored as more ‘scared/worried’, while outdoor-raised piglets spent more time eating and jumping against the arena walls. Both groups interacted with a plastic ball (challenge 2: exposure to a novel object) during which they were scored as more ‘playful/curious’ than other challenges. When a food bowl was introduced (challenge 3), farrowing shed-raised piglets were more interested in playing with the food bowl itself, whereas outdoor-raised piglets spent more time eating the feed. Finally, there were no significant differences in social behaviour (challenge 4: introduction of another piglet) between the two groups in terms of the latency to contact each other, amount of time recorded engaged in aggressive/non-aggressive social interactions or QBA scores. Although piglets spent 30% of their time interacting with the other piglet, and half of this time (47%) was engaged in negative interactions (pushing, biting), the levels of aggression were not different between the two groups. Overall, outdoor-raised piglets ate more and were scored as more ‘calm/passive’, whereas farrowing shed-raised piglets spent more time investigating their environment and were scored as more ‘playful/inquisitive’. In conclusion, we did not find differences in behaviour between outdoor-raised and farrowing shed-raised piglets that would highlight welfare issues. The differences found in this study may reflect conflicting affective states, with responses to confinement, neophobia and motivation for exploration evident.
Childhood depressive symptoms may arise from genetic and environmental risks, which act to bias the ways in which children process emotional information. Previous studies show that several “cognitive biases” are heritable and share genetic and environmental risks with depressive symptoms. Past research suggests that many cognitive biases only reflect genetic risks for depressive symptoms from adolescence. The present study sought to identify (a) when interpersonal cognitions mature as risk factors for depressive symptoms by examining whether these factors are stable and predict symptoms across time in childhood, and (b) the extent to which interpersonal cognitions reflect inherited/environmental risks on children's depressive symptoms. Results showed that there was some stability for interpersonal cognitive biases from age 8 to 10 years (rs = .32–.43). Only the absence of positive self/other perceptions, and negative peer and mother expectations at age 8 predicted depressive symptoms at age 10 (after controlling for depressive symptoms at age 8). The absence of positive self/other perceptions shared genetic influences with depressive symptoms within and across time. Across middle to late childhood, interpersonal cognitions begin to operate as vulnerability-trait factors for depressive symptoms, gradually reflecting distal genetic risks on symptoms.
Specific roles of individual CDPKs vary, but in general they mediate essential biological functions necessary for parasite survival. A comparative analysis of the structure-activity relationships (SAR) of Neospora caninum, Eimeria tenella and Babesia bovis calcium-dependent protein kinases (CDPKs) together with those of Plasmodium falciparum, Cryptosporidium parvum and Toxoplasma gondii was performed by screening against 333 bumped kinase inhibitors (BKIs). Structural modelling and experimental data revealed that residues other than the gatekeeper influence compound–protein interactions resulting in distinct sensitivity profiles. We subsequently defined potential amino-acid structural influences within the ATP-binding cavity for each orthologue necessary for consideration in the development of broad-spectrum apicomplexan CDPK inhibitors. Although the BKI library was developed for specific inhibition of glycine gatekeeper CDPKs combined with low inhibition of threonine gatekeeper human SRC kinase, some library compounds exhibit activity against serine- or threonine-containing CDPKs. Divergent BKI sensitivity of CDPK homologues could be explained on the basis of differences in the size and orientation of the hydrophobic pocket and specific variation at other amino-acid positions within the ATP-binding cavity. In particular, BbCDPK4 and PfCDPK1 are sensitive to a larger fraction of compounds than EtCDPK1 despite the presence of a threonine gatekeeper in all three CDPKs.
This article extends Lau and Redlawsk's notion of correct voting – whether voters, under conditions of uncertainty, choose the alternative they would have chosen had they been fully informed about the issues and candidates in that election – to sixty-nine elections in thirty-three established and emerging democracies around the world. At the individual level, political sophistication, political experience and motivation all significantly predict the probability of casting a correct vote. However several institutional factors proved to be even more important. In particular, elections with more parties running – and settings that encourage candidate-centred voting – decrease the probability of correct voting, while more ideologically distinctive alternatives, clearer lines of responsibility and greater media access to information are associated with higher rates of correct voting.
Natural and synthetic hydroxyapatite (HA) scaffolds for potential
load-bearing bone implants were fabricated by two methods. The natural
scaffolds were formed by heating bovine cancellous bone at 1325°C, which
removed the organic and sintered the HA. The synthetic scaffolds were
prepared by freeze-casting HA powders, using different solid loadings (20–35
vol.%) and cooling rates (1–10°C/min). Both types of scaffolds were
infiltrated with polymethylmethacrylate (PMMA). The porosity, pore size, and
compressive mechanical properties of the natural and synthetic scaffolds
were investigated and compared to that of natural cortical and cancellous
bone. Prior to infiltration, the sintered cancellous scaffolds exhibited
pore sizes of 100 – 300 μm, a strength of 0.4 – 9.7 MPa, and a Young’s
modulus of 0.1 – 1.2 GPa. The freeze-casted scaffolds had pore sizes of 10 –
50 μm, strengths of 0.7 – 95.1 MPa, and Young’s moduli of 0.1 –19.2 GPa.
When infiltrated with PMMA, the cancellous bone- PMMA composite showed a
strength of 55 MPa and a Young’s modulus of 4.5 GPa. Preliminary data for
the synthetic HA-PMMA composite showed a strength of 42 MPa and a modulus of