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Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up.
Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models.
Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups.
These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.
We describe the design and deployment of GREENBURST, a commensal Fast Radio Burst (FRB) search system at the Green Bank Telescope. GREENBURST uses the dedicated L-band receiver tap to search over the 960–1 920 MHz frequency range for pulses with dispersion measures out to
. Due to its unique design, GREENBURST is capable of conducting searches for FRBs when the L-band receiver is not being used for scheduled observing. This makes it a sensitive single pixel detector capable of reaching deeper in the radio sky. While single pulses from Galactic pulsars and rotating radio transients will be detectable in our observations, and will form part of the database we archive, the primary goal is to detect and study FRBs. Based on recent determinations of the all-sky rate, we predict that the system will detect approximately one FRB for every 2–3 months of continuous operation. The high sensitivity of GREENBURST means that it will also be able to probe the slope of the FRB fluence distribution, which is currently uncertain in this observing band.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
The warm, equable, and ice-free early Eocene Epoch permits investigation of ecosystem function and macro-ecological patterns during a very different climate regime than exists today. It also provides insight into what the future may entail, as anthropogenic CO2 release drives Earth toward a comparable hothouse condition. Studying plant–insect herbivore food webs during hothouse intervals is warranted, because these account for the majority of nonmicrobial terrestrial biodiversity. Here, we report new plant and insect herbivore damage census data from two floodplain sites in the Wind River Basin of central Wyoming, one in the Aycross Formation (50–48.25 Ma) at the basin edge (WRE) and the second in the Wind River Formation in the interior of the basin (WRI). The WRI site is in stratigraphic proximity to a volcanic ash that is newly dated to 52.416 ± 0.016/0.028/0.063 (2σ). We compare the Wind River Basin assemblages to published data from a 52.65 Ma floodplain flora in the neighboring Bighorn (BH) Basin and find that only 5.6% of plant taxa occur at all three sites and approximately 10% occur in both basins. The dissimilar floras support distinct suites of insect herbivores, as recorded by leaf damage. The relatively low-diversity BH flora has the highest diversity of insect damage, contrary to hypotheses that insect herbivore diversity tracks floral diversity. The distinctiveness of the WRE flora is likely due to its younger age and cooler reconstructed paleotemperature, but these factors are nearly identical for the WRI and BH floras. Site-specific microenvironmental factors that cannot be measured easily in deep time may account for these differences. Alternatively, the Owl Creek Mountains between the two basins may have provided a formidable barrier to the thermophilic organisms that inhabited the basin interiors, supporting Janzen's hypothesis that mountain passes appear higher in tropical environments.
We present a numerical methodology for construction of reduced-order models (ROMs) of fluid flows through the combination of flow modal decomposition and regression analysis. Spectral proper orthogonal decomposition is applied to reduce the dimensionality of the model and, at the same time, filter the proper orthogonal decomposition temporal modes. The regression step is performed by a deep feedforward neural network (DNN), and the current framework is implemented in a context similar to the sparse identification of nonlinear dynamics algorithm. A discussion on the optimization of the DNN hyperparameters is provided for obtaining the best ROMs and an assessment of these models is presented for a canonical nonlinear oscillator and the compressible flow past a cylinder. Then the method is tested on the reconstruction of a turbulent flow computed by a large eddy simulation of a plunging airfoil under dynamic stall. The reduced-order model is able to capture the dynamics of the leading edge stall vortex and the subsequent trailing edge vortex. For the cases analysed, the numerical framework allows the prediction of the flow field beyond the training window using larger time increments than those employed by the full-order model. We also demonstrate the robustness of the current ROMs constructed via DNNs through a comparison with sparse regression. The DNN approach is able to learn transient features of the flow and presents more accurate and stable long-term predictions compared to sparse regression.
Cardiovascular disease is a leading cause of morbidity and mortality in childhood cancer survivors. Cardiologists must be aware of risk factors and long-term follow-up guidelines, which have historically been the purview of oncologists. Little is known about paediatric cardiologists’ knowledge regarding the cardiotoxicity of cancer treatment and how to improve this knowledge.
A total of 58 paediatric cardiologists anonymously completed a 21-question, web-based survey focused on four cardio-oncology themes: cancer treatment-related risk factors (n = 6), patient-related risk factors (n = 6), recommended surveillance (n = 3), and cardiac-specific considerations (n = 6). Following the baseline survey, a multi-disciplinary team of paediatric cardiologists and cancer survivor providers developed an in-person and web-based educational intervention. A post-intervention survey was conducted 5 months later.
The response rate was 41/58 (70.7%) pre-intervention and 30/58 (51.7%) post-intervention. On the baseline survey, the percentage of correct answers was 68.8 ± 10.3%, which improved to 79.2 ± 16.2% after the intervention (p = 0.009). The theme with the most profound knowledge deficit was surveillance; however, it also had the greatest improvement after the intervention (49.6 ± 26.7 versus 66.7 ± 27.7% correct, p = 0.025). Individual questions with the largest per cent improvement pertained to risk of cardiac dysfunction with time since treatment (52.4 versus 93.1%, p = 0.002) and the role of dexrazoxane (48.8 versus 82.8%, p = 0.020).
Specific knowledge deficits about the care of paediatric cancer survivors were identified amongst cardiologists using a web-based survey. Knowledge of surveillance was initially lowest but improved the most after an educational intervention. This highlights the need for cardio-oncology-based educational initiatives among paediatric cardiologists.
Current techniques for measuring the dry matter intake (DMI) of grazing lactating beef cows are invasive, time consuming and expensive making them impractical for use on commercial farms. This study was undertaken to explore the potential to develop and validate a model to predict DMI of grazing lactating beef cows, which could be applied in a commercial farm setting, using non-invasive animal measurements. The calibration dataset used to develop the model was comprised of 94 measurements recorded on 106 beef or beef–dairy crossbred cows (maternal origin). The potential of body measurements, linear type scoring, grazing behaviour and thermal imaging to predict DMI in combination with known biologically plausible adjustment variables and energy sinks was investigated. Multivariable regression models were constructed for each independent variable using SAS PROC REG and contained milk yield, BW, parity, calving day and maternal origin (dairy or beef). Of the 94 variables tested, 32 showed an association with DMI (P < 0.25) upon multivariable analysis. These variables were incorporated into a backwards linear regression model using SAS PROC REG. Variables were retained in this model if P < 0.05. Five variables; width at pins, full body depth, ruminating mastications, central ligament and rump width score, were retained in the model in addition to milk yield, BW, parity, calving day and maternal origin. The inclusion of these variables in the model increased the predictability of DMI by 0.23 (R2 = 0.68) when compared to a model containing milk yield, BW, parity, calving day and maternal origin only. This model was applied to data recorded on an independent dataset; a herd of 60 lactating beef cows two years after the calibration study. The R2 for the validation was 0.59. Estimates of DMI are required for measuring feed efficiency. While acknowledging challenges in applicability, the findings suggest a model such as that developed in this study may be used as a tool to more easily and less invasively estimate DMI on large populations of commercial beef cows, and therefore measure feed efficiency.
We present an account of why we decided to retract a paper. We discovered a lack of adherence to conventional trials registration, execution, interpretation and reporting, and consequently, with the authors, needed to correct the scientific record. We set out our responses in general to strengthen research integrity.
Declaration of interest
K.S.B. is Editor-in-Chief of the British Journal of Psychiatry. W.L., K.R.K. and S.M.L. are members of the senior editorial committee and the research integrity committee for the journal. In the past three years, S.M.L. has received research support from Janssen and Lundbeck, and personal support from Janssen, Otsuka and Sunovion.
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
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.
We provide the first in situ measurements of antenna element beam shapes of the Murchison Widefield Array. Most current processing pipelines use an assumed beam shape, which can cause absolute and relative flux density errors and polarisation ‘leakage’. Understanding the primary beam is then of paramount importance, especially for sensitive experiments such as a measurement of the 21-cm line from the epoch of reionisation, where the calibration requirements are so extreme that tile to tile beam variations may affect our ability to make a detection. Measuring the primary beam shape from visibilities is challenging, as multiple instrumental, atmospheric, and astrophysical factors contribute to uncertainties in the data. Building on the methods of Neben et al. [Radio Sci., 50, 614], we tap directly into the receiving elements of the telescope before any digitisation or correlation of the signal. Using ORBCOMM satellite passes we are able to produce all-sky maps for four separate tiles in the XX polarisation. We find good agreement with the beam model of Sokolowski et al. [2017, PASA, 34, e062], and clearly observe the effects of a missing dipole from a tile in one of our beam maps. We end by motivating and outlining additional on-site experiments.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
The prevalence of mental disorders among Black, Latino, and Asian adults is lower than among Whites. Factors that explain these differences are largely unknown. We examined whether racial/ethnic differences in exposure to traumatic events (TEs) or vulnerability to trauma-related psychopathology explained the lower rates of psychopathology among racial/ethnic minorities.
We estimated the prevalence of TE exposure and associations with onset of DSM-IV depression, anxiety and substance disorders and with lifetime post-traumatic stress disorder (PTSD) in the Collaborative Psychiatric Epidemiology Surveys, a national sample (N = 13 775) with substantial proportions of Black (35.9%), Latino (18.9%), and Asian Americans (14.9%).
TE exposure varied across racial/ethnic groups. Asians were most likely to experience organized violence – particularly being a refugee – but had the lowest exposure to all other TEs. Blacks had the greatest exposure to participation in organized violence, sexual violence, and other TEs, Latinos had the highest exposure to physical violence, and Whites were most likely to experience accidents/injuries. Racial/ethnic minorities had lower odds ratios of depression, anxiety, and substance disorder onset relative to Whites. Neither variation in TE exposure nor vulnerability to psychopathology following TEs across racial/ethnic groups explained these differences. Vulnerability to PTSD did vary across groups, however, such that Asians were less likely and Blacks more likely to develop PTSD following TEs than Whites.
Lower prevalence of mental disorders among racial/ethnic minorities does not appear to reflect reduced vulnerability to TEs, with the exception of PTSD among Asians. This highlights the importance of investigating other potential mechanisms underlying racial/ethnic differences in psychopathology.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.
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.
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.