To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
The Murchison Widefield Array (MWA) is an electronically steered low-frequency (<300 MHz) radio interferometer, with a ‘slew’ time less than 8 s. Low-frequency (∼100 MHz) radio telescopes are ideally suited for rapid response follow-up of transients due to their large field of view, the inverted spectrum of coherent emission, and the fact that the dispersion delay between a 1 GHz and 100 MHz pulse is on the order of 1–10 min for dispersion measures of 100–2000 pc/cm3. The MWA has previously been used to provide fast follow-up for transient events including gamma-ray bursts (GRBs), fast radio bursts (FRBs), and gravitational waves, using systems that respond to gamma-ray coordinates network packet-based notifications. We describe a system for automatically triggering MWA observations of such events, based on Virtual Observatory Event standard triggers, which is more flexible, capable, and accurate than previous systems. The system can respond to external multi-messenger triggers, which makes it well-suited to searching for prompt coherent radio emission from GRBs, the study of FRBs and gravitational waves, single pulse studies of pulsars, and rapid follow-up of high-energy superflares from flare stars. The new triggering system has the capability to trigger observations in both the regular correlator mode (limited to ≥0.5 s integrations) and using the Voltage Capture System (VCS, 0.1 ms integration) of the MWA and represents a new mode of operation for the MWA. The upgraded standard correlator triggering capability has been in use since MWA observing semester 2018B (July–Dec 2018), and the VCS and buffered mode triggers will become available for observing in a future semester.
Ethnic minority groups often have more complex and aversive pathways to mental health care. However, large population-based studies are lacking, particularly regarding involuntary hospitalisation. We sought to examine the risk of involuntary admission among first-generation ethnic minority groups with early psychosis in Ontario, Canada.
Using health administrative data, we constructed a retrospective cohort (2009–2013) of people with first-onset non-affective psychotic disorder aged 16–35 years. This cohort was linked to immigration data to ascertain migrant status and country of birth. We identified the first involuntary admission within 2 years and compared the risk of involuntary admission for first-generation migrant groups to the general population. To control for the role of migrant status, we restricted the sample to first-generation migrants and examined differences by country of birth, comparing risk of involuntary admission among ethnic minority groups to a European reference. We further explored the role of migrant class by adjusting for immigrant vs refugee status within the migrant cohort. We also explored effect modification of migrant class by ethnic minority group.
We identified 15 844 incident cases of psychotic disorder, of whom 19% (n = 3049) were first-generation migrants. Risk of involuntary admission was higher than the general population in five of seven ethnic minority groups. African and Caribbean migrants had the highest risk of involuntary admission (African: risk ratio (RR) = 1.52, 95% CI = 1.34–1.73; Caribbean: RR = 1.58, 95% CI = 1.37–1.82), and were the only groups where the elevated risk persisted when compared to the European reference group within the migrant cohort (African: RR = 1.24, 95% CI = 1.04–1.48; Caribbean: RR = 1.29, 95% CI = 1.07–1.56). Refugee status was independently associated with involuntary admission (RR = 1.16, 95% CI = 1.02–1.32); however, this risk varied by ethnic minority group, with Caribbean refugees having an elevated risk of involuntary admission compared with Caribbean immigrants (RR = 1.72, 95% CI = 1.15–2.58).
Our findings are consistent with the international literature showing increased rates of involuntary admission among some ethnic minority groups with early psychosis. Interventions aimed at improving pathways to care could be targeted at these groups to reduce disparities.
Social anxiety lies on a continuum, and young adults with elevated symptoms are at risk for developing a range of psychiatric disorders. Yet relatively little is known about the factors that govern the hour-by-hour experience and expression of social anxiety in the real world.
Here we used smartphone-based ecological momentary assessment (EMA) to intensively sample emotional experience across different social contexts in the daily lives of 228 young adults selectively recruited to represent a broad spectrum of social anxiety symptoms.
Leveraging data from over 11 000 real-world assessments, our results highlight the central role of close friends, family members, and romantic partners. The presence of such close companions was associated with enhanced mood, yet socially anxious individuals had fewer confidants and spent less time with the close companions that they do have. Although higher levels of social anxiety were associated with a general worsening of mood, socially anxious individuals appear to derive larger benefits – lower levels of negative affect, anxiety, and depression – from their close companions. In contrast, variation in social anxiety was unrelated to the amount of time spent with strangers, co-workers, and acquaintances; and we uncovered no evidence of emotional hypersensitivity to these less-familiar individuals.
These findings provide a framework for understanding the deleterious consequences of social anxiety in emerging adulthood and set the stage for developing improved intervention strategies.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
To assess the effect of topical betahistine on Eustachian tube function in subjectively abnormal subjects in a hyperbaric chamber.
Active and passive Eustachian tube function was examined using tympanometry in a pressure chamber.
Active Eustachian tube function was tested against the negative middle ear pressure induced by increasing the chamber pressure to +3 kPa. One voluntary swallow decreased middle-ear pressure by a mean of 1.36 kPa. Passive Eustachian tube function was tested by measuring spontaneous Eustachian tube openings as the chamber pressure dropped from +10 kPa to ambient. Four distinct patterns of Eustachian tube behaviour were seen, three of which indicated Eustachian tube dysfunction. Betahistine had no positive effect on Eustachian tube opening, although previous animal studies had suggested a beneficial effect.
Topical betahistine had no effect on Eustachian tube function. Combining a hyperbaric chamber with tympanometry proved ideal for evaluating Eustachian tube function.
Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.
A new combination in Vachellia is published for Acacia pennivenia. A summation of the current state of knowledge of this Socotran endemic species is presented, including a morphological description, a distribution map and an updated conservation assessment. Colour photographs and a black-and-white line drawing are presented.
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
The low-frequency polarisation properties of radio sources are poorly studied, particularly in statistical samples. However, the new generation of low-frequency telescopes, such as the Murchison Widefield Array (the precursor for the low-frequency component of the Square Kilometre Array) offers an opportunity to probe the physics of radio sources at very low radio frequencies. In this paper, we present a catalogue of linearly polarised sources detected at 216 MHz, using data from the Galactic and Extragalactic All-sky Murchison Widefield Array survey. Our catalogue covers the Declination range –17° to –37° and 24 h in Right Ascension, at a resolution of around 3 arcminutes. We detect 81 sources (including both a known pulsar and a new pulsar candidate) with linearly polarised flux densities in excess of 18 mJy across a survey area of approximately 6 400 deg2, corresponding to a surface density of 1 source per 79 deg2. The level of Faraday rotation measured for our sources is broadly consistent with those recovered at higher frequencies, with typically more than an order of magnitude improvement in the uncertainty compared to higher-frequency measurements. However, our catalogue is likely incomplete at low Faraday rotation measures, due to our practice of excluding sources in the region where instrumental leakage appears. The majority of sources exhibit significant depolarisation compared to higher frequencies; however, a small sub-sample repolarise at 216 MHz. We also discuss the polarisation properties of four nearby, large-angular-scale radio galaxies, with a particular focus on the giant radio galaxy ESO 422–G028, in order to explain the striking differences in polarised morphology between 216 MHz and 1.4 GHz.
The family physician is key to facilitating access to psychiatric treatment for young people with first-episode psychosis, and this involvement can reduce aversive events in pathways to care. Those who seek help from primary care tend to have longer intervals to psychiatric care, and some people receive ongoing psychiatric treatment from the family physician.
Our objective is to understand the role of the family physician in help-seeking, recognition and ongoing management of first-episode psychosis.
We will use a mixed-methods approach, incorporating health administrative data, electronic medical records (EMRs) and qualitative methodologies to study the role of the family physician at three points on the pathway to care. First, help-seeking: we will use health administrative data to examine access to a family physician and patterns of primary care use preceding the first diagnosis of psychosis; second, recognition: we will identify first-onset cases of psychosis in health administrative data, and look back at linked EMRs from primary care to define a risk profile for undetected cases; and third, management: we will examine service provision to identified patients through EMR data, including patterns of contacts, prescriptions and referrals to specialised care. We will then conduct qualitative interviews and focus groups with key stakeholders to better understand the trends observed in the quantitative data.
These findings will provide an in-depth description of first-episode psychosis in primary care, informing strategies to build linkages between family physicians and psychiatric services to improve transitions of care during the crucial early stages of psychosis.
Discrepancies between population-based estimates of the incidence of psychotic disorder and the treated incidence reported by early psychosis intervention (EPI) programs suggest additional cases may be receiving services elsewhere in the health system. Our objective was to estimate the incidence of non-affective psychotic disorder in the catchment area of an EPI program, and compare this to EPI-treated incidence estimates.
We constructed a retrospective cohort (1997–2015) of incident cases of non-affective psychosis aged 16–50 years in an EPI program catchment using population-based linked health administrative data. Cases were identified by either one hospitalization or two outpatient physician billings within a 12-month period with a diagnosis of non-affective psychosis. We estimated the cumulative incidence and EPI-treated incidence of non-affective psychosis using denominator data from the census. We also estimated the incidence of first-episode psychosis (people who would meet the case definition for an EPI program) using a novel approach.
Our case definition identified 3245 cases of incident non-affective psychosis over the 17-year period. We estimate that the incidence of first-episode non-affective psychosis in the program catchment area is 33.3 per 100 000 per year (95% CI 31.4–35.1), which is more than twice as high as the EPI-treated incidence of 18.8 per 100 000 per year (95% CI 17.4–20.3).
Case ascertainment strategies limited to specialized psychiatric services may substantially underestimate the incidence of non-affective psychotic disorders, relative to population-based estimates. Accurate information on the epidemiology of first-episode psychosis will enable us to more effectively resource EPI services and evaluate their coverage.
The essays in this volume provide a new perspective on the history of convicts and penal colonies. They demonstrate that the nineteenth and twentieth centuries were a critical period in the reconfiguration of empires, imperial governmentality, and punishment, including through extensive punitive relocation and associated extractive labour. Ranging across the global contexts of Africa, Asia, Australasia, Japan, the Americas, the Pacific, Russia, and Europe, and exploring issues of criminalization, political repression, and convict management alongside those of race, gender, space, and circulation, this collection offers a perspective from the colonies that radically transforms accepted narratives of the history of empire and the history of punishment. In this introduction, we argue that a colony-centred perspective reveals that, during a critical period in world history, convicts and penal colonies created new spatial hierarchies, enabled the incorporation of territories into spheres of imperial influence, and forged new connections and distinctions between “metropoles” and “colonies”. Convicts and penal colonies enabled the formation of expansive and networked global configurations and processes, a factor hitherto unappreciated in the literature.
The ‘Digital Index of North American Archaeology’ (DINAA) project demonstrates how the aggregation and publication of government-held archaeological data can help to document human activity over millennia and at a continental scale. These data can provide a valuable link between specific categories of information available from publications, museum collections and online databases. Integration improves the discovery and retrieval of records of archaeological research currently held by multiple institutions within different information systems. It also aids in the preservation of those data and makes efforts to archive these research results more resilient to political turmoil. While DINAA focuses on North America, its methods have global applicability.
Objectives: Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. Methods: Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. Results: In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. Conclusions: This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention. (JINS, 2018, 24, 445–455)
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.
To evaluate the long-term safety/tolerability and efficacy of deutetrabenazine in patients with TD. Week 54 open-labelresults are reported in this interim analysis.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safetymeasures included incidence of adverse events (AEs), serious AEs (SAEs), drug-related AEs, and AEs leading to withdrawal, dose reduction, or dose suspension. This analysis reports results up to Week 54.
304 patients enrolled in the extension study. There were 215 patient-years of exposure in this analysis, and exposure-adjusted incidence rates (EAIRs) of AEs (incidence/patient-years) were comparable to or lower than those observed with short-term deutetrabenazine treatment and placebo. The frequency of SAEs (EAIR 0.14) was similar to rates observed with short-termplacebo (EAIR 0.33) and deutetrabenazine (EAIR range 0.06–0.33) treatment. AEs leading to study discontinuation (EAIR 0.08), dose reduction (EAIR 0.17), and dose suspension (EAIR 0.09) were uncommon.
Long-term treatment with deutetrabenazine was generally safe and well tolerated in patients with TD, and did not result in cumulative toxicity.
Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
Tardive dyskinesia (TD) is an involuntary movement disorder resulting from exposure to dopamine-receptor antagonists. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.
To evaluate the efficacy and safety of long-term deutetrabenazine therapy in patients with TD.
Patients with TD who completed the ARM-TD or AIM-TD studies were eligible to enter this open-label, single-arm, long-term safety study after they completed the 1-week washout period and final evaluation in the blinded portion of the trial. Efficacy endpoints included the change in AIMS score from baseline, and treatment success (defined as “much improved” or “very much improved”) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC). This analysis reports results up to Week 54.
304 patients enrolled in the extension study. At Week 54, the mean (standard error) change in AIMS score was –5.1 (0.52). After 6 weeks of deutetrabenazine treatment, the proportion of patients who achieved treatment success was 58% per the CGIC and 53% per the PGIC, and by Week 54 was 72% per the CGIC and 59% per the PGIC, thus demonstrating maintenance or enhancement of benefit over time. Deutetrabenazine was well tolerated for up to 54 weeks, and compared with the ARM-TD and AIM-TD studies, no new safety signals were detected.
54 weeks of deutetrabenazine treatment was generally efficacious, safe, and well tolerated in patients with TD.
Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
Tardive dyskinesia (TD) is an involuntary movement disorder that is often irreversible, can affect any body region, and can be debilitating. In the ARM-TDand AIM-TD studies, deutetrabenazine treatment demonstrated statistically and clinically significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo (primary endpoint).
To evaluate the efficacy of deutetrabenazine, as measured by the Clinical Global Impression of Change (CGIC) scale, in patients with TD from the pooled ARM-TDand AIM-TD (24 and 36 mg/day doses) data sets, as compared with the pooled placebo cohort.
ARM-TD and AIM-TD were 12-week, randomized, double-blind, placebo-controlled studies that evaluated the safety and efficacy of deutetrabenazine for thetreatment of TD. The key secondary endpoint of each study was the proportion of patients “much improved” or “very much improved” (treatment success) at Week 12 on theCGIC.
At Week 12, the odds of treatment success among patients treated with deutetrabenazine (n=152) was more than double that of patients given placebo (n=107; odds ratio: 2.12; P=0.005). In a categorical analysis of CGIC ratings, patients treated with deutetrabenazine showed greater improvement than patients given placebo (P=0.003). Patients treated with deutetrabenazine also had a significantly better treatment response than those given placebo (least-squares mean CGIC score treatment difference: –0.4; P=0.006).
Deutetrabenazine treatment led to statistically and clinically significant improvements in TD symptoms based on the CGIC result, suggesting that clinicians were able to recognize the benefit in patients treated with deutetrabenazine.
Presented at: The International Congress of Parkinson’s Disease and Movement Disorders; June 4–8, 2017; Vancouver, British Columbia, Canada.
These studies were funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.