We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save 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 saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
Background: Neck vessel imaging is often performed in hyperacute stroke to allow neurointerventionalists to estimate access complexity. This study aimed to assess clinician agreement on catheterization strategies based on imaging in these scenarios. Methods: An electronic portfolio of 60 patients with acute ischemic stroke was sent to 53 clinicians. Respondents were asked: (1) the difficulty of catheterization through femoral access with a regular Vertebral catheter, (2) whether to use a Simmons or reverse-curve catheter initially, and (3) whether to consider an alternative access site. Agreement was assessed using Fleiss’ Kappa statistics. Results: Twenty-two respondents (7 neurologists, 15 neuroradiologists) completed the survey. Overall there was slight interrater agreement (κ=0.17, 95% CI: 0.10–0.25). Clinicians with >50 cases annually had better agreement (κ=0.22) for all questions than those with fewer cases (κ=0.07). Agreement did not significantly differ by imaging modality: CTA (κ=0.18) and MRA (κ=0.14). In 40/59 cases (67.80%), at least 25% of clinicians disagreed on whether to use a Simmons or reverse-curve catheter initially. Conclusions: Agreement on catheterization strategies remains fair at best. Our results suggest that visual assessment of pre-procedural vessels imaging is not reliable for the estimation of endovascular access complexity.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.
Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
We provide an assessment of the Infinity Two fusion pilot plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio $A = 10$, quasi-isodynamic stellarator with improved confinement appealing to a max-$J$ approach, elevated plasma density and high magnetic fields ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. At the envisioned operating point ($800$ MW deuterium-tritium (DT) fusion), the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed helium-cooled pebble bed is TBR $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.
In this work, we present a detailed assessment of fusion-born alpha-particle confinement, their wall loads and stability of Alfvén eigenmodes driven by these energetic particles in the Infinity Two Fusion Pilot Plant baseline plasma design, a four-field-period quasi-isodynamic stellarator to operate in deuterium–tritium fusion conditions. Using the Monte Carlo codes, SIMPLE, ASCOT5 and KORC-T, we study the collisionless and collisional dynamics of guiding-centre and full-orbit alpha-particles in the core plasma. We find that core energy losses to the wall are less than 4 %. Our simulations shows that peak power loads on the wall of this configuration are approximately 2.5 MW m-$^2$ and are spatially localised, toroidally and poloidaly, in the vicinity of x-points of the magnetic island chain $n/m = 4/5$ outside the plasma volume. Also, an exploratory analysis using various simplified walls shows that shaping and distance of the wall from the plasma volume can help reduce peak power loads. Our stability assessment of Alfvén eigenmodes using the STELLGAP and FAR3d codes shows the absence of unstable modes driven by alpha-particles in Infinity Two due to the relatively low alpha-particle beta at the envisioned 800 MW operating scenario.
The magnetohydrodynamic (MHD) equilibrium and stability properties of the Infinity Two fusion pilot plant baseline plasma physics design are presented. The configuration is a four-field period, aspect ratio $A = 10$ quasi-isodynamic stellarator optimised for excellent confinement at elevated density and high magnetic field $B = 9\,T$. Magnetic surfaces exist in the plasma core in vacuum and retain good equilibrium surface integrity from vacuum to an operational $\beta = 1.6 \,\%$, the ratio of the volume average of the plasma and magnetic pressures, corresponding to $800\ \textrm{MW}$ deuterium–tritium fusion operation. Neoclassical calculations show that a self-consistent bootstrap current of the order of ${\sim} 1\ \textrm{kA}$ slightly increases the rotational transform profile by less than 0.001. The configuration has a magnetic well across its entire radius. From vacuum to the operating point, the configuration exhibits good ballooning stability characteristics, exhibits good Mercier stability across most of its minor radius and it is stable against global low-n MHD instabilities up to $\beta = 3.2\,\%$.
Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.
We present a novel scheme for rapid quantitative analysis of debris generated during experiments with solid targets following relativistic laser–plasma interaction at high-power laser facilities. Results are supported by standard analysis techniques. Experimental data indicate that predictions by available modelling for non-mass-limited targets are reasonable, with debris of the order of hundreds of μg per shot. We detect for the first time two clearly distinct types of debris emitted from the same interaction. A fraction of the debris is ejected directionally, following the target normal (rear and interaction side). The directional debris ejection towards the interaction side is larger than on the side of the target rear. The second type of debris is characterized by a more spherically uniform ejection, albeit with a small asymmetry that favours ejection towards the target rear side.
We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.
Global disruption, technological advances, and population demographics are rapidly affecting the types of jobs that are available and the workers who will fill those jobs in the future of work. Successful workers in the dynamic and uncertain landscape of the workplace of the future will need to adapt rapidly to changing job demands, highlighting the necessity for lifelong learning and development. With few exceptions, industrial-organizational (I-O) psychologists have tended to take an organization-centered perspective on training and development; a perspective that promotes worker development as a means to organizational success. Hence, we call for a broadening of this view to include a person-centered perspective on workplace learning focused on individual skill development. A person-centered perspective addresses lifelong learning and skill development for those already in the labor force, whether they are working within or outside of organizations (e.g., gig workers), or those looking for work. It includes the most vulnerable people currently working or seeking work. We describe the factors affecting the future of work, the need to incorporate a person-centered perspective on work-related skill learning into I-O research and practice, and highlight several areas for future research and practice.
Understanding the physics of electromagnetic pulse (EMP) emission and nozzle damage is critical for the long-term operation of laser experiments with gas targets, particularly at facilities looking to produce stable sources of radiation at high repetition rates. We present a theoretical model of plasma formation and electrostatic charging when high-power lasers are focused inside gases. The model can be used to estimate the amplitude of gigahertz EMPs produced by the laser and the extent of damage to the gas jet nozzle. Looking at a range of laser and target properties relevant to existing high-power laser systems, we find that EMP fields of tens to hundreds of kV/m can be generated several metres from the gas jet. Model predictions are compared with measurements of EMPs, plasma formation and nozzle damage from two experiments on the VEGA-3 laser and one experiment on the Vulcan Petawatt laser.
This article discusses alternative procedures to the standard F-test for ANCOVA in case the covariate is measured with error. Both a functional and a structural relationship approach are described. Examples of both types of analysis are given for the simple two-group design. Several cases are discussed and special attention is given to issues of model identifiability. An approximate statistical test based on the functional relationship approach is described. On the basis of Monte Carlo simulation results it is concluded that this testing procedure is to be preferred to the conventional F-test of the ANCOVA null hypothesis. It is shown how the standard null hypothesis may be tested in a structural relationship approach. It is concluded that some knowledge of the reliability of the covariate is necessary in order to obtain meaningful results.
This study reveals the usefulness of multiple correlation techniques in estimating the relative importance of different aspects of a tracking task in the operator's tracking behavior. The technique is applied to a compensatory tracking task with a position control.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines Therapeutic-Clinical Working Group members gathered critical recommendations in follow-up to lessons learned manuscripts released earlier in the COVID-19 pandemic. Lessons around agent prioritization, preclinical therapeutics testing, master protocol design and implementation, drug manufacturing and supply, data sharing, and public–private partnership value are shared to inform responses to future pandemics.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
Gaming disorder has become a global concern and it could have a variety of health and social consequences. The trauma model has been applied to the understanding of different types of addictions as behavioral addictions can sometimes be conceptualized as self-soothing strategies to avoid trauma-related stressors or triggers. However, much less is known about the relationship between trauma exposure and gaming disorder.
Objectives
To inform prevention and intervention strategies and to facilitate further research, we conducted the first scoping review to explore and summarize the literature on the relationship between trauma and gaming disorder.
Methods
A systematic search was conducted on the Web of Science, Scopus and ProQuest. We looked for original studies published in English that included a measure of trauma exposure and a measure of gaming disorder symptoms, as well as quantitative data regarding the relationship between trauma exposure and gaming disorder.
Results
The initial search generated 412 articles, of which 15 met the inclusion criteria. All of them were cross-sectional studies, recruiting participants from both clinical and non-clinical populations. Twelve of them (80%) reported significant correlations between trauma exposure and the severity of gaming disorder symptoms (r = 0.18 to 0.46, p < 0.010). Several potential mediators, including depressive symptoms and dissociative experiences, have been identified. One study found that parental monitoring moderated the relationship between trauma and gaming disorder symptoms. No studies reported the prevalence of trauma or trauma-related symptoms among people with gaming disorder.
Conclusions
There is some evidence supporting the association between trauma and gaming disorder, at small to medium effect sizes. Future studies should investigate the mediators and moderators underlying the relationship between trauma and gaming disorder. The longitudinal relationship between trauma exposure and the development of gaming disorder should be clarified. A trauma-informed approach may be a helpful strategy to alleviate gaming disorder symptoms.
Panic disorder (PD) and agoraphobia (AG) are highly comorbid anxiety disorders with an increasing prevalence that have a significant clinical and public health impact but are not adequately recognized and treated. Although the current functional neuroimaging literature has documented a range of neural abnormalities in these disorders, primary studies are often not sufficiently powered and their findings have been inconsistent.
Objectives
This meta-analysis aims to advance our understanding of the neural underpinnings of PD and AG by identifying the most robust patterns of differential neural activation that differentiate individuals diagnosed with one of or both these disorders from age-matched healthy controls.
Methods
We conducted a comprehensive literature search in the PubMed database for all peer-reviewed, whole-brain, task-based functional magnetic resonance imaging (fMRI) activation studies that compared adults diagnosed with PD and/or AG with age-matched healthy controls. Each of these articles was screened by two independent coding teams using formal inclusion criteria and according to current PRISMA guidelines. We then performed a voxelwise, whole-brain, meta-analytic comparison of PD/AG participants with age-matched healthy controls using multilevel kernel density analysis (MKDA) with ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias and 10,000 Monte Carlo simulations to correct for multiple comparisons.
Results
With data from 34 primary studies and a substantial sample size (N=2138), PD/AG participants, relative to age-matched healthy controls, exhibited a reliable pattern of statistically significant, (p<.05-0.0001; FWE-corrected) abnormal neural activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
In this meta-analysis we found robust patterns of differential neural activation in participants diagnosed with PD/AG relative to age-matched healthy controls. These findings advance our understanding of the neural underpinnings of PD and AG and inform the development of brain-based clinical interventions such as non-invasive brain stimulation (NIBS) and treatment prediction and matching algorithms. Future studies should also investigate the neural similarities and differences between PD and AG to increase our understanding of possible differences in their etiology, diagnosis, and treatment.
Bipolar I disorder (BD-I) is a chronic and recurrent mood disorder characterized by alternating episodes of depression and mania; it is also associated with substantial morbidity and mortality and with clinically significant functional impairments. While previous studies have used functional magnetic resonance imaging (fMRI) to examine neural abnormalities associated with BD-I, they have yielded mixed findings, perhaps due to differences in sampling and experimental design, including highly variable mood states at the time of scan.
Objectives
The purpose of this study is to advance our understanding of the neural basis of BD-I and mania, as measured by fMRI activation studies, and to inform the development of more effective brain-based diagnostic systems and clinical treatments.
Methods
We conducted a large-scale meta-analysis of whole-brain fMRI activation studies that compared participants with BD-I, assessed during a manic episode, to age-matched healthy controls. Following PRISMA guidelines, we conducted a comprehensive PubMed literature search using two independent coding teams to evaluate primary studies according to pre-established inclusion criteria. We then used multilevel kernel density analysis (MKDA), a well-established, voxel-wise, whole-brain, meta-analytic approach, to quantitatively synthesize all qualifying primary fMRI activation studies of mania. We used ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias, and 10,000 Monte Carlo simulations to correct for multiple comparisons.
Results
We found that participants with BD-I (N=2,042), during an active episode of mania and relative to age-matched healthy controls (N=1,764), exhibit a pattern of significantly (p<0.05-0.0001; FWE-corrected) different activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
This study supports the formulation of a robust neural basis for BD-I during manic episodes and advances our understanding of the pattern of abnormal activation in this disorder. These results may inform the development of novel brain-based clinical tools for bipolar disorder such as diagnostic biomarkers, non-invasive brain stimulation, and treatment-matching protocols. Future studies should compare the neural signatures of BD-I to other related disorders to facilitate the development of protocols for differential diagnosis and improve treatment outcomes in patients with BD-I.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric condition that frequently originates in early development and is associated with a variety of functional impairments. Despite a large functional neuroimaging literature on ADHD, our understanding of the neural basis of this disorder remains limited, and existing primary studies on the topic include somewhat divergent results.
Objectives
The present meta-analysis aims to advance our understanding of the neural basis of ADHD by identifying the most statistically robust patterns of abnormal neural activation throughout the whole-brain in individuals diagnosed with ADHD compared to age-matched healthy controls.
Methods
We conducted a meta-analysis of task-based functional magnetic resonance imaging (fMRI) activation studies of ADHD. This included, according to PRISMA guidelines, a comprehensive PubMed search and predetermined inclusion criteria as well as two independent coding teams who evaluated studies and included all task-based, whole-brain, fMRI activation studies that compared participants diagnosed with ADHD to age-matched healthy controls. We then performed multilevel kernel density analysis (MKDA) a well-established, whole-brain, voxelwise approach that quantitatively combines existing primary fMRI studies, with ensemble thresholding (p<0.05-0.0001) and multiple comparisons correction.
Results
Participants diagnosed with ADHD (N=1,550), relative to age-matched healthy controls (N=1,340), exhibited statistically significant (p<0.05-0.0001; FWE-corrected) patterns of abnormal activation in multiple brains of the cerebral cortex and basal ganglia across a variety of cognitive control tasks.
Conclusions
This study advances our understanding of the neural basis of ADHD and may aid in the development of new brain-based clinical interventions as well as diagnostic tools and treatment matching protocols for patients with ADHD. Future studies should also investigate the similarities and differences in neural signatures between ADHD and other highly comorbid psychiatric disorders.