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Cognitive deficits affect a significant proportion of patients with bipolar disorder (BD). Problems with sustained attention have been found independent of mood state and the causes are unclear. We aimed to investigate whether physical parameters such as activity levels, sleep, and body mass index (BMI) may be contributing factors.
Forty-six patients with BD and 42 controls completed a battery of neuropsychological tests and wore a triaxial accelerometer for 21 days which collected information on physical activity, sleep, and circadian rhythm. Ex-Gaussian analyses were used to characterise reaction time distributions. We used hierarchical regression analyses to examine whether physical activity, BMI, circadian rhythm, and sleep predicted variance in the performance of cognitive tasks.
Neither physical activity, BMI, nor circadian rhythm predicted significant variance on any of the cognitive tasks. However, the presence of a sleep abnormality significantly predicted a higher intra-individual variability of the reaction time distributions on the Attention Network Task.
This study suggests that there is an association between sleep abnormalities and cognition in BD, with little or no relationship with physical activity, BMI, and circadian rhythm.
We present a calibration component for the Murchison Widefield Array All-Sky Virtual Observatory (MWA ASVO) utilising a newly developed PostgreSQL database of calibration solutions. Since its inauguration in 2013, the MWA has recorded over 34 petabytes of data archived at the Pawsey Supercomputing Centre. According to the MWA Data Access policy, data become publicly available 18 months after collection. Therefore, most of the archival data are now available to the public. Access to public data was provided in 2017 via the MWA ASVO interface, which allowed researchers worldwide to download MWA uncalibrated data in standard radio astronomy data formats (CASA measurement sets or UV FITS files). The addition of the MWA ASVO calibration feature opens a new, powerful avenue for researchers without a detailed knowledge of the MWA telescope and data processing to download calibrated visibility data and create images using standard radio astronomy software packages. In order to populate the database with calibration solutions from the last 6 yr we developed fully automated pipelines. A near-real-time pipeline has been used to process new calibration observations as soon as they are collected and upload calibration solutions to the database, which enables monitoring of the interferometric performance of the telescope. Based on this database, we present an analysis of the stability of the MWA calibration solutions over long time intervals.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged antipsychotic use. RE KINECT, a real-world screening study of antipsychotic-treated outpatients, included patients with movements that were clinician-confirmed as possible TD (Cohort 2) and patients with no involuntary movements (Cohort 1). Baseline data from the patient rated EuroQoL 5-Dimension 5-Level questionnaire (EQ-5D-5L) and Sheehan Disability Scale (SDS) were analyzed to evaluate health related quality of life (Cohort 2 vs. Cohort 1) and the effects of possible TD on quality of life (Cohort 2).
Assessments included EQ-5D-5L utility score (0=equivalent to death to 1=perfect health); SDS total score (0=no impact to 30=highest impact); patient- and clinician-rated severity of possible TD in 4 body regions (0=none, 1=some, and 2=a lot; summary score, 0 to 8); and patient-rated impact of possible TD in 7 daily activities (0=none, 1=some, and 2=a lot; summary score, 0 to 14). Populations included Cohort 1 (N=450); full Cohort 2 (N=204); and limited Cohort 2 (N=111, patients who self-reported “some” or “a lot” of TD severity in ≥1 body region). Mean differences between Cohort 2 and Cohort 1 in EQ-5D-5L utility and SDS total scores were analyzed using a generalized linear regression model that was adjusted for potentially confounding factors (e.g., age, sex, psychiatric diagnosis). Associations between TD summary scores (severity, impact) and quality of life (EQ-5D-5L utility, SDS total) were analyzed using a regression model.
The mean score difference between full Cohort 2 (N=204) and Cohort 1 (N=450) was significant for EQ-5D-5L utility (-0.037; P<0.05 [adjusted analysis]) but not SDS total (0.267; P>0.05). However, when limited to Cohort 2 patients who self-reported “a lot” of TD severity (n=53) or impact (n=33), both EQ 5D 5L utility and SDS total scores were significantly worse than in Cohort 1 (P<0.05). Regression coefficients indicated significant associations between patient-rated impact and EQ 5D-5L utility in the full Cohort 2 (-0.021, P<0.001) and limited Cohort 2 (-0.024, P<0.001). A significant association was also found with patient rated severity in limited Cohort 2 (P<0.05), but not with clinician-rated severity. Similar results were found for SDS total score.
RE-KINECT patients were consistent in evaluating the severity and impact of TD, whether based on subjective assessments or standardized patient-reported instruments (EQ-5D-5L, SDS). Clinician-rated severity of TD may not always correlate with patient perceptions of the significance of TD. Patient self-assessments (focused on symptom impact) can be clinically relevant; incorporating such measures into everyday practice may provide a more comprehensive approach to TD assessment and management.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
The climate crisis requires nations to achieve human well-being with low national levels of carbon emissions. Countries vary from one another dramatically in how effectively they convert resources into well-being, and some nations with low levels of emissions have relatively high objective and subjective well-being. We identify urgent research and policy agendas for four groups of countries with either low or high emissions and well-being indicators. Least studied are those with low well-being and high emissions. Understanding social and political barriers to switching from high-carbon to lower-carbon modes of production and consumption, and ways to overcome them, will be fundamental.
Tardive dyskinesia (TD) is a hyperkinetic movement disorder associated with antipsychotic treatment. RE KINECT (NCT03062033), a real-world study of outpatients prescribed antipsychotics, was designed to identify the presence of possible TD and characterize the impact of involuntary movements on functioning and quality of life. Data from RE-KINECT were used to compare the impact of possible TD in patients with schizophrenia/schizoaffective disorder [SZD] versus mood/other psychiatric disorders [Mood].
Adults with ≥3months of lifetime exposure to antipsychotics and ≥1 psychiatric disorder were recruited. The presence of possible TD was based on clinicians’ observation of involuntary movements in 4 body regions (head, trunk, upper extremities, and lower extremities). Baseline outcomes included demographics, medication history, location/severity of abnormal movements, impact of abnormal movements on daily activities, the Sheehan Disability Scale (SDS), and the EuroQoL 5-Dimensional questionnaire (EQ-5D-5L).
Of 204 patients with clinician-confirmed possible TD, 111 (54.4%) had a SZD diagnosis and 93 (45.6%) had a mood/other psychiatric diagnosis. Significant differences found between groups (Mood vs SZD) included: mean age (56.9 vs 52.7 years; P=0.0263); male sex (33.3% vs 62.2%; P<0.0001); African-American race (7.5% vs 26.1%; P=0.0005); mean lifetime exposure to antipsychotics (9.5 vs 19.5 years; P<0.0001); and percentage of patients currently taking ≥2 psychiatric medications (93.5% vs 79.3%; P=0.0093). Based on clinician observation, there were no significant differences between diagnosis groups in the number of body regions impacted by abnormal movements, maximum severity score across all 4 regions, or patient awareness of possible TD. Over 30% of patients in both groups reported that involuntary movements had “some” or “a lot” of impact on their ability to continue usual activities, be productive, and socialize. No significant differences between the diagnosis groups (Mood vs SZD) were found for mean SDS total score (12.8 vs 10.8), SDS domain scores (work/school [4.1 vs 4.2], social life [4.3 vs 3.7], family life [4.1 vs 3.5]), EQ-5D-5L utility score (0.68 vs 0.74), or EQ-5D-5L health state VAS (64.8 vs 68.5).
In this cohort of outpatients with possible TD, those with Mood disorders were more likely to be older, female, and white than patients with SZD. The ability to function and quality of life were equally impaired in both groups. Further studies on the impact of TD are needed.
Funding Acknowledgements: Neurocrine Biosciences, Inc.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
A 3-yr watermelon experiment was established in fall 2013 to evaluate cover crop, polyethylene mulch, tillage, and herbicide application components for weed control, yield, and profitability. Conservation tillage, either with a cereal rye cover crop alone or integrated with polyethylene mulch, was compared to the standard industry practice of conventional tillage with bedded polyethylene mulch. The study also used a non-bedded conventional tillage system without polyethylene to determine polyethylene and cover crop residue effects. Within each of the four systems, herbicide treatments comprised halosulfuron applied (1) at 26.3 g ai ha–1 PRE, (2) at 26.3 g ai ha–1 POST, or (3) sequentially at 26.3 g ai ha–1 PRE and POST. Each system also had a nontreated control. In addition, clethodim was applied in all plots twice POST at 140 g ai ha–1, except for nontreated in each system. In 2014, polyethylene or cereal rye cover crop effectively controlled tall morningglory, coffee senna, and carpetweed early season in nontreated plots, whereas the integration of the two was effective at controlling common purslane. Tall morningglory and purslane control was insufficient late season regardless of production system and herbicide application. In 2015, polyethylene effectively controlled cutleaf eveningprimrose, sicklepod, and arrowleaf sida early season in nontreated plots. Yellow nutsedge control was insufficient late season regardless of production system and herbicide application. Utilizing sequential halosulfuron applications did not increase weed control over PRE or POST alone in all years. Polyethylene use resulted in yields higher than systems without in all years. Across all 3 yr, net returns were highest for polyethylene mulch systems. The results of this experiment underscore the need for more progress in developing integrated conservation systems for watermelon production. Effective herbicides, low-disturbance cultivation, and/or hand weeding are most likely the key to success in conservation specialty crop systems.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
We use deep Chandra and HST data to uniquely classify the X-ray binary (XRB) populations in M81 on the basis of their donor stars and local stellar populations (into early-type main sequence, yellow giant, supergiant, low-mass, and globular cluster). First, we find that more massive, redder, and denser globular clusters are more likely to be associated with XRBs. Second, we find that the high-mass XRBs (HMXBs) overall have a steeper X-ray luminosity function (XLF) than the canonical star-forming galaxy XLF, though there is some evidence of variations in the slopes of the sub-populations. On the other hand, the XLF of the prototypical starburst M82 is described by the canonical powerlaw (αcum ∼ 0.6) down to LX ∼ 1036 erg s−1. We attribute variations in XLF slopes to different mass transfer modes (Roche-lobe overflow versus wind-fed systems).
We analyse the vertical distribution of High Mass X-ray Binaries (HMXBs) in NGC 55, the nearest edge-on galaxy to the Milky Way. Our analysis reveals significant spatial offsets of HMXBs from the star forming regions, greater than those observed in the SMC and the LMC but similar with the Milky Way. The spatial offsets can be explained by a momentum kick the X-ray binaries receive during the formation of the compact object. The difference between the scale height of the vertical distribution of HMXBs and the vertical distribution of star-forming activity is 0.48±0.04 kpc. The centre-of-mass velocity of the distribution of HMXBs in NGC 55 is moving at a velocity of 52.4±11.4 km s−1, greater than the corresponding velocity of HMXBs in the SMC and LMC, but consistent with velocities of Milky Way HMXBs.
Cognitive theories of generalised anxiety disorder (GAD) posit that cognitive and behavioural factors maintain the disorder. This study examined whether avoidance and safety behaviours mediated the relationship between cognitive factors and GAD symptoms. We also examined the reverse mediation model; that is, whether cognitive factors mediated the relationship between maladaptive behaviours and GAD symptoms. Undergraduate psychology students (N = 125 and N = 292) completed the Worry Behaviours Inventory (a recently developed measure of maladaptive behaviours associated with GAD), in addition to measures of intolerance of uncertainty, cognitive avoidance, metacognitive beliefs, and symptoms of GAD and depression. Analyses supported the reliability and validity of the WBI. We consistently found that engagement in maladaptive behaviours significantly mediated the relationship between cognitive factors and symptoms of GAD. The reverse mediation model was also supported. Our results are consistent with the contention that cognitive and behavioural factors contribute to GAD symptom severity.
The Pediatric Heart Network designed a career development award to train the next generation of clinician scientists in paediatric-cardiology-related research, a historically underfunded area. We sought to identify the strengths/weaknesses of the programme and describe the scholars’ academic achievements and the network’s return on investment.
Survey questions designed to evaluate the programme were sent to applicants – 13 funded and 19 unfunded applicants – and 20 mentors and/or principal investigators. Response distributions were calculated. χ2 tests of association assessed differences in ratings of the application/selection processes among funded scholars, unfunded applicants, and mentors/principal investigators. Scholars reported post-funding academic achievements.
Survey response rates were 88% for applicants and 100% for mentor/principal investigators. Clarity and fairness of the review were rated as “clear/fair” or “very clear/very fair” by 98% of respondents, but the responses varied among funded scholars, unfunded applicants, and mentors/principal investigators (clarity χ2=10.85, p=0.03; fairness χ2=16.97, p=0.002). Nearly half of the unfunded applicants rated feedback as “not useful” (47%). “Expanding their collaborative network” and “increasing publication potential” were the highest-rated benefits for scholars. Mentors/principal investigators found the programme “very” valuable for the scholars (100%) and the network (75%). The 13 scholars were first/senior authors for 97 abstracts and 109 manuscripts, served on 22 Pediatric Heart Network committees, and were awarded $9,673,660 in subsequent extramural funding for a return of ~$10 for every scholar dollar spent.
Overall, patient satisfaction with the Scholar Award was high and scholars met many academic markers of success. Despite this, programme challenges were identified and improvement strategies were developed.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
Background: Cognitive models of generalized anxiety disorder (GAD) suggest that maladaptive behaviours may contribute to the maintenance of the disorder; however, little research has concentrated on identifying and measuring these behaviours. To address this gap, the Worry Behaviors Inventory (WBI) was developed and has been evaluated within a classical test theory (CTT) approach. Aims: As CTT is limited in several important respects, this study examined the psychometric properties of the WBI using an Item Response Theory approach. Method: A large sample of adults commencing treatment for their symptoms of GAD (n = 537) completed the WBI in addition to measures of GAD and depression symptom severity. Results: Patients with a probable diagnosis of GAD typically engaged in four or five maladaptive behaviours most or all of the time in an attempt to prevent, control or avoid worrying about everyday concerns. The two-factor structure of the WBI was confirmed, and the WBI scales demonstrated good reliability across a broad range of the respective scales. Together with previous findings, our results suggested that hypervigilance and checking behaviours, as well as avoidance of saying or doing things that are worrisome, were the most relevant maladaptive behaviours associated with GAD, and discriminated well between adults with low, moderate and high degrees of the respective WBI scales. Conclusions: Our results support the importance of maladaptive behaviours to GAD and the utility of the WBI to index these behaviours. Ramifications for the classification, theoretical conceptualization and treatment of GAD are discussed.