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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.
Mass Gathering Medicine focuses on mitigating issues at Mass Gathering Events. Medical skills can vary substantially among staff, and the literature provides no specific guidance on staff training. This study highlights expert opinions on minimum training for medical staff to formalize preparation for a mass gathering.
Methods
This is a 3-round Delphi study. Experts were enlisted at Mass Gathering conferences, and researchers emailed participation requests through Stat59 software. Consent was obtained verbally and on Stat59 software. All responses were anonymous. Experts generated opinions. The second and third rounds used a 7-point linear ranking scale. Statements reached a consensus if the responses had a standard deviation (SD) of less than or equal to 1.0.
Results
Round 1 generated 137 open-ended statements. Seventy-three statements proceeded to round 2. 28.7% (21/73) found consensus. In round 3, 40.3% of the remaining statements reached consensus (21/52). Priority themes included venue-specific information, staff orientation to operations and capabilities, and community coordination. Mass casualty preparation and triage were also highlighted as a critical focus.
Conclusions
This expert consensus framework emphasizes core training areas, including venue-specific operations, mass casualty response, triage, and life-saving skills. The heterogeneity of Mass Gatherings makes instituting universal standards challenging. The conclusions highlight recurrent themes of priority among multiple experts.
After Hurricane Ida, faith-based organizations were vital to disaster response. However, this community resource remains understudied. This exploratory study examines local faith-based organizational involvement in storm recovery by evaluating response activities, prevalence and desire for formal disaster education, coordination with other organizations, effect of storm damage on response, and observations for future response.
Methods
An exploratory survey was administered to community leaders throughout the Bayou Region of Louisiana consisting of questions regarding demographics, response efforts, coordination with other organizations, formal disaster training, the impact of storm damage on ability to respond, and insights into future response.
Results
Faith-based organizations are active during storm response. There is a need and desire for formal disaster education. Many organizations experienced storm damage but continued serving their community. Other emerging themes included: importance of clear communications, building stronger relationships with other organizations prior to a disaster, and coordination of resources.
Conclusions
Faith-based organizations serve an important role in disaster response. Though few have formal training, they are ready and present in the area of impact, specifically in hurricane response. In the midst of organizational and personal damage, these organizations respond quickly and effectively to provide a necessary part of the disaster management team.
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.
The global population and status of Snowy Owls Bubo scandiacus are particularly challenging to assess because individuals are irruptive and nomadic, and the breeding range is restricted to the remote circumpolar Arctic tundra. The International Union for Conservation of Nature (IUCN) uplisted the Snowy Owl to “Vulnerable” in 2017 because the suggested population estimates appeared considerably lower than historical estimates, and it recommended actions to clarify the population size, structure, and trends. Here we present a broad review and status assessment, an effort led by the International Snowy Owl Working Group (ISOWG) and researchers from around the world, to estimate population trends and the current global status of the Snowy Owl. We use long-term breeding data, genetic studies, satellite-GPS tracking, and survival estimates to assess current population trends at several monitoring sites in the Arctic and we review the ecology and threats throughout the Snowy Owl range. An assessment of the available data suggests that current estimates of a worldwide population of 14,000–28,000 breeding adults are plausible. Our assessment of population trends at five long-term monitoring sites suggests that breeding populations of Snowy Owls in the Arctic have decreased by more than 30% over the past three generations and the species should continue to be categorised as Vulnerable under the IUCN Red List Criterion A2. We offer research recommendations to improve our understanding of Snowy Owl biology and future population assessments in a changing world.
Daily sodium intake in England is ∼3.3 g/day(1), with government and scientific advice to reduce intake for cardiovascular health purposes having varying success(2). Eccrine sweat is produced during exercise or exposure to warm environments to maintain body temperature through evaporative cooling. Sweat is primarily water, but also contains appreciable amounts of electrolytes, particularly sodium, meaning sweat sodium losses could reduce daily sodium balance without the need for dietary manipulation. However, the effects of sweat sodium losses on 24-h sodium balance are unclear.
Fourteen active participants (10 males, 4 females; 23±2 years, 45±9 mL/kg/min) completed a preliminary trial and two 24-h randomised, counterbalanced experimental trials. Participants arrived fasted for baseline (0-h) measures (blood/urine samples, blood pressure, nude body mass) followed by breakfast and low-intensity intermittent cycling in the heat (∼36⁰C, ∼50% humidity) to turnover ∼2.5% body mass in sweat (EX), or the same duration of room temperature seated rest (REST). Further blood samples were collected post-EX/REST (1.5-3 h post-baseline). During EX, sweat was collected from 5 sites and water consumed to fully replace sweat losses. During REST, participants drank 100 mL/h. Food intake was individually standardised over the 24-h, with bottled water available ad-libitum. Participants collected all urine produced over the 24-h and returned the following morning to repeat baseline measures fasted (24-h). Sodium balance was estimated over the 24-h using sweat/urine losses and dietary intake. Data were analysed using 2-way ANOVA followed by Shapiro-Wilk and paired t-tests/Wilcoxon signed-rank tests. Data are mean (standard deviation).
Dietary sodium intake was 2.3 (0.3) g and participants lost 2.8 (0.3) % body mass in sweat (containing 2.5 (0.9) g sodium). Sodium balance was lower for EX (-2.0 (1.6) g vs -1.0 (1.6) g; P = 0.022), despite lower 24-h urine sodium losses in EX (1.8 (1.2) g vs 3.3 (1.7) g; P = 0.001). PostEX/REST blood sodium concentration was lower in EX (137.6 (2.3) mmol/L vs 139.9 (1.0) mmol/L; P = 0.002) but did not differ at 0-h (P = 0.906) or 24-h (P = 0.118). There was no difference in plasma volume change (P = 0.423), urine specific gravity (P = 0.495), systolic (P = 0.324) or diastolic (P = 0.274) blood pressure between trials over the 24-h. Body mass change over 24-h was not different between trials (REST +0.25 (1.10) %; EX +0.40 (0.68) %; P = 0.663).
Sweat loss through low-intensity exercise resulted in a lower sodium balance compared to rest. Although urine sodium output reduced with EX, it was not sufficient to offset exercise-induced sodium losses. Despite this, body mass, plasma volume and blood sodium concentration were not different between trials, suggesting sodium may have been lost from non-osmotic sodium stores. This suggests sweat sodium losses could be used to reduce sodium balance, although longer studies are required to confirm this thesis.
Early adversity increases risk for child mental health difficulties. Stressors in the home environment (e.g., parental mental illness, household socioeconomic challenges) may be particularly impactful. Attending out-of-home childcare may buffer or magnify negative effects of such exposures. Using a longitudinal observational design, we leveraged data from the NIH Environmental influences on Child Health Outcomes Program to test whether number of hours in childcare, defined as 1) any type of nonparental care and 2) center-based care specifically, was associated with child mental health, including via buffering or magnifying associations between early exposure to psychosocial and socioeconomic risks (age 0–3 years) and later internalizing and externalizing symptoms (age 3–5.5 years), in a diverse sample of N = 2,024 parent–child dyads. In linear regression models, childcare participation was not associated with mental health outcomes, nor did we observe an impact of childcare attendance on associations between risk exposures and symptoms. Psychosocial and socioeconomic risks had interactive effects on internalizing and externalizing symptoms. Overall, the findings did not indicate that childcare attendance positively or negatively influenced child mental health and suggested that psychosocial and socioeconomic adversity may need to be considered as separate exposures to understand child mental health risk in early life.
This study analyzes disparities in initial health care responses in Turkey and Syria following the 2023 earthquakes.
Methods
Using Humanitarian Data Exchange, Crude Mortality Rates (CMR) and injury rates in both countries were calculated, and temporal trends of death tolls and injuries in the first month post- catastrophe were compared. World Health Organization (WHO) Flash Appeal estimated funding requirements, and ratios of humanitarian aid personnel in Urban Search and Rescue (USAR) teams per population from ReliefWeb and MAPACTION data were used to gauge disparities.
Results
56 051 096 individuals were exposed, with Turkey having 44 million vs 12 million in Syria. Turkey had higher CMR in affected areas (10.5 vs. 5.0 per 10,000), while Syria had higher CMR in intensely seismic regions (9.3 vs. 7.7 per 1,000). Turkey had higher injury rates (24.6 vs. 9.9 per 10 000). Death and injury rates plateaued in Syria after 3 days, but steadily rose in Turkey. Syria allocated more funding for all priorities per population except health care facilities’ rehabilitation. Turkey had 219 USAR teams compared to Syria’s 6, with significantly more humanitarian aid personnel (23 vs. 2/100,000).
Conclusions
Significant disparities in the initial health care response were observed between Turkey and Syria, highlighting the need for policymakers to enhance response capabilities in conflict-affected events to reduce the impact on affected populations.
Narrative Abstract
The 2023 Turkish-Syrian earthquakes, the most devastating in the region since 1939, heightened challenges in Syria’s health care system amid ongoing conflict, disrupting Gaziantep’s humanitarian aid supply route. The initial health care responses post-earthquakes in Turkey and Syria were analyzed through a descriptive study, where Crude Mortality Rates (CMR) and injury rates during the first week were calculated. The World Health Organization’s funding priorities and the ratio of humanitarian aid personnel in Urban Search and Rescue teams per population were assessed. Turkey had 4-fold higher earthquake exposure and experienced higher CMR and injuries per population, while Syria had higher CMR in intensely seismic regions. Temporal trends showed plateaued death and injury rates in Syria within 3 days, while Turkey’s continued to increase. Syria required more funding across nearly all priorities while Turkey had more humanitarian aid personnel per population. Significant health care response disparities were observed, emphasizing the imperative for policymakers to enhance initial responses in conflict-affected events.
Major depressive disorder (MDD) is a tremendous global disease burden and the leading cause of disability worldwide. Unfortunately, individuals diagnosed with MDD typically experience a delayed response to traditional antidepressants and many do not adequately respond to pharmacotherapy, even after multiple trials. The critical need for novel antidepressant treatments has led to a recent resurgence in the clinical application of psychedelics, and intravenous ketamine, which has been investigated as a rapid-acting treatment for treatment resistant depression (TRD) as well acute suicidal ideation and behavior. However, variations in the type and quality of experimental design as well as a range of treatment outcomes in clinical trials of ketamine make interpretation of this large body of literature challenging.
Objectives
This umbrella review aims to advance our understanding of the effectiveness of intravenous ketamine as a pharmacotherapy for TRD by providing a systematic, quantitative, large-scale synthesis of the empirical literature.
Methods
We performed a comprehensive PubMed search for peer-reviewed meta-analyses of primary studies of intravenous ketamine used in the treatment of TRD. Meta-analysis and primary studies were then screened by two independent coding teams according to pre-established inclusion criteria as well as PRISMA and METRICS guidelines. We then employed metaumbrella, a statistical package developed in R, to perform effect size calculations and conversions as well as statistical tests.
Results
In a large-scale analysis of 1,182 participants across 51 primary studies, repeated-dose administration of intravenous ketamine demonstrated statistically significant effects (p<0.05) compared to placebo-controlled as well as other experimental conditions in patients with TRD, as measured by standardized clinician-administered and self-report depression symptom severity scales.
Conclusions
This study provides large-scale, quantitative support for the effectiveness of intravenous, repeated-dose ketamine as a therapy for TRD and a report of the relative effectiveness of several treatment parameters across a large and rapidly growing literature. Future investigations should use similar analytic tools to examine evidence-stratified conditions and the comparative effectiveness of other routes of administration and treatment schedules as well as the moderating influence of other clinical and demographic variables on the effectiveness of ketamine on TRD and suicidal ideation and behavior.
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.
There has been rapidly growing interest in understanding the pharmaceutical and clinical properties of psychedelic and dissociative drugs, with a particular focus on ketamine. This compound, long known for its anesthetic and dissociative properties, has garnered attention due to its potential to rapidly alleviate symptoms of depression, especially in individuals with treatment-resistant depression (TRD) or acute suicidal ideation or behavior. However, while ketamine’s psychopharmacological effects are increasingly well-documented, the specific patterns of its neural impact remain a subject of exploration and basic questions remain about its effects on functional activation in both clinical and healthy populations.
Objectives
This meta-analysis seeks to contribute to the evolving landscape of neuroscience research on dissociative drugs such as ketamine by comprehensively examining the effects of acute ketamine administration on neural activation, as measured by functional magnetic resonance imaging (fMRI), in healthy participants.
Methods
We conducted a meta-analysis of existing fMRI activation studies of ketamine using multilevel kernel density analysis (MKDA). Following a comprehensive PubMed search, we quantitatively synthesized all published primary fMRI whole-brain activation studies of the effects of ketamine in healthy subjects with no overlapping samples (N=18). This approach also incorporated ensemble thresholding (α=0.05-0.0001) to minimize cluster-size detection bias and Monte Carlo simulations to correct for multiple comparisons.
Results
Our meta-analysis revealed statistically significant (p<0.05-0.0001; FWE-corrected) alterations in neural activation in multiple cortical and subcortical regions following the administration of ketamine to healthy participants (N=306).
Conclusions
These results offer valuable insights into the functional neuroanatomical effects caused by acute ketamine administration. These findings may also inform development of therapeutic applications of ketamine for various psychiatric and neurological conditions. Future studies should investigate the neural effects of ketamine administration, including both short-term and long-term effects, in clinical populations and their relation to clinical and functional improvements.
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.
An electrooptic birefringence technique was employed to study the effect of particle size, saturating cation, and clay type on the rotational diffusion coefficient (a measure of the rate at which the particles rotate or relax within the solution) from a preferred orientation. These studies help elucidate the nature of the cation—water environment near the clay particles.
Previous work has shown that some clay particles orient at both low and high voltages due to a permanent dipole and an induced dipole, respectively, whereas other clays under similar short-duration pulses orient only at high voltages. The permanent dipole was attributed to the iron in the octahedral layer of the clay mineral, whereas the induced dipole was probably due to a redistribution of the diffuse double-layer cations. This study shows that smaller clay particles orient more readily at low voltages and have greater rotational diffusion coefficients at high voltages. The higher the rotational diffusion coefficient, the faster the particles move in their surrounding water-cation environment. The effect of the saturating cation on the rotational diffusion coefficients was Na > Li > K for the permanent dipole and K > Li > Na > Ca > Mg for the induced dipole orientation. Previous results (Schepers and Miller, 1974) are interpreted to mean that a particle in dilute suspension can rotate independently of its environment only when the salt concentration in the surrounding medium approaches zero. At higher salt concentrations, or if the particle environment is perturbed by an electric field, the particle rotates with a water shell. As the concentration of salt or strength of the electric field increases further, either the viscosity of the surrounding solution increases or the size of the rotating shell is greatly increased. Thus, the water around clay particles appears to be structurally different than normal, and this condition is probably caused by the nature of the clay—cation interaction.
FTIR studies of six partially-deuterated montmorillonites (MS) reveal the presence of two O-D stretching bands, one between 2702–2728 cm-1 and another near 2680 cm-1. For homoionic (Li, Na, Mg, Ca, or La) Wyoming-type MS, the position of the higher frequency band, designated as (O-D)h, is between 2714–2728 cm-1, whereas for homoionic Cheto-type MS it is between 2702–2706 cm-1. The lower frequency band, designated as (O-D)1, is in the narrow range of 2674–2684 cm-1. Resolution of two corresponding O-H bands, appearing near 3670 and 3635 cm-1, was observed only after partial dehydroxylation of the smectites. The changes in the relative intensities of the two O-D stretching bands as a function of the smectite type and of the Lewis acidity (charge density) of the exchangeable ion were determined. For Wyoming-type MS, the intensity of the (O-D)h band is much lower than that of the (O-D)l band, whereas for Cheto-type MS, the intensity of the (O-D)h band is about equal or slightly higher than that of the (O-D)l band. The observed resolution can be ascribed tentatively to the presence of (at least) two types of octahedral OH groups in the smectites, the (O-D)h band being assigned to AlMgOH and the (O-D)1 band to AlAlOH groups. Pillaring of Cheto-type MS with hydroxy-Al13 oligocations resulted in products showing much higher thermal stability between 400–600°C compared to that of identically pillared Wyoming-type MS. Compositional and other factors, e.g., CEC values and mode of pillaring, may cause this difference in stability.
Assessment of performance validity during neuropsychology evaluation is essential to reliably interpret cognitive test scores. Studies (Webber et al., 2018; Wisdom, et al., 2012) have validated the use of abbreviated measures, such as Trial 1 (T1) of the Test of Memory Malingering (TOMM), to detect invalid performance. Only one study (Bauer et al., 2007) known to these authors has examined the utility of Green’s Word Memory Test (WMT) immediate recall (IR) as a screening tool for invalid performance. This study explores WMT IR as an independent indicator of performance validity in a mild TBI (mTBI) veteran population.
Participants and Methods:
Participants included 211 (Mage = 32.1, SD = 7.4; Medu = 13.1, SD = 1.64; 94.8% male; 67.8% White) OEF/OIF/OND veterans with a history of mTBI who participated in a comprehensive neuropsychological evaluation at one of five participating VA Medical Centers. Performance validity was assessed using validated cut scores from the following measures: WMT IR and delayed recall (DR); TOMM T1; WAIS-IV reliable digit span; CVLT-II forced choice raw score; Wisconsin Card Sorting Test failure to maintain set; and the Rey Memory for Fifteen Items test, combo score. Sensitivity and specificity were calculated for each IR score compared with failure on DR. In addition, sensitivity and specificity were calculated for each WMT IR score compared to failure of at least one additional performance validity measure (excluding DR), two or more measures, and three or more measures, respectively.
Results:
Results indicated that 46.8% participants failed to meet cut offs for adequate performance validity based on the standard WMT IR cut score (i.e., 82.5%; M = 81.8%, SD = 17.7%); however, 50.2% participants failed to meet criteria based on the standard WMT DR cut score (M = 79.8% SD = 18.6%). A cut score of 82.5% or below on WMT IR correctly identified 82.4% (i.e., sensitivity) of subjects who performed below cut score on DR, with a specificity of 94.2%. Examination of IR cutoffs compared to failure of one or more other PVTs revealed that the standardized cut score of 82.5% or below had a sensitivity of 78.2% and a specificity of 72.4%; whereas, a cut score of 65% or below had a sensitivity of 41% and a specificity of 91.3%. Similarly, examination of IR cutoffs compared to failure of two or more additional PVTs revealed that the cut score of 60% or below had a sensitivity of 45.7% and specificity of 93.1% ; whereas, a cut score of 57.5% or below had a sensitivity of 57.9% and specificity of 90.9% when using failure of three or more PVTs as the criterion.
Conclusions:
Results indicated that a cut score of 82.5% or below on WMT IR may be sufficient to detect invalid performance when considering WMT DR as criterion. Furthermore, WMT IR alone, with adjustments to cut scores, appears to be a reasonable way to assess symptom validity compared to other PVTs. Sensitivity and specificity of WMT IR scores may have been adversely impacted by lower sensitivity of other PVTs to independently identify invalid performance.
We present and evaluate the prospects for detecting coherent radio counterparts to gravitational wave (GW) events using Murchison Widefield Array (MWA) triggered observations. The MWA rapid-response system, combined with its buffering mode ($\sim$4 min negative latency), enables us to catch any radio signals produced from seconds prior to hours after a binary neutron star (BNS) merger. The large field of view of the MWA ($\sim$$1\,000\,\textrm{deg}^2$ at 120 MHz) and its location under the high sensitivity sky region of the LIGO-Virgo-KAGRA (LVK) detector network, forecast a high chance of being on-target for a GW event. We consider three observing configurations for the MWA to follow up GW BNS merger events, including a single dipole per tile, the full array, and four sub-arrays. We then perform a population synthesis of BNS systems to predict the radio detectable fraction of GW events using these configurations. We find that the configuration with four sub-arrays is the best compromise between sky coverage and sensitivity as it is capable of placing meaningful constraints on the radio emission from 12.6% of GW BNS detections. Based on the timescales of four BNS merger coherent radio emission models, we propose an observing strategy that involves triggering the buffering mode to target coherent signals emitted prior to, during or shortly following the merger, which is then followed by continued recording for up to three hours to target later time post-merger emission. We expect MWA to trigger on $\sim$$5-22$ BNS merger events during the LVK O4 observing run, which could potentially result in two detections of predicted coherent emission.
Meta-analyses of functional magnetic resonance imaging (fMRI) studies have been used to elucidate the most reliable neural features associated with various psychiatric disorders. However, it has not been well-established whether each of these neural features is linked to a specific disorder or is transdiagnostic across multiple disorders and disorder categories, including mood, anxiety, and anxiety-related disorders.
Objectives
This project aims to advance our understanding of the disorder-specific and transdiagnostic neural features associated with mood, anxiety, and anxiety-related disorders as well as to refine the methodology used to compare multiple disorders.
Methods
We conducted an exhaustive PubMed literature search followed by double-screening, double-extraction, and cross-checking to identify all whole-brain, case-control fMRI activation studies of mood, anxiety, and anxiety-related disorders in order to construct a large-scale meta-analytic database of primary studies of these disorders. We then employed multilevel kernel density analysis (MKDA) with Monte-Carlo simulations to correct for multiple comparisons as well as ensemble thresholding to reduce cluster size bias to analyze primary fMRI studies of mood, anxiety, and anxiety-related disorders followed by application of triple subtraction techniques and a second-order analysis to elucidate the disorder-specificity of the previously identified neural features.
Results
We found that participants diagnosed with mood, anxiety, and anxiety-related disorders exhibited statistically significant (p < .05 – 0.0001; FWE-corrected) differences in neural activation relative to healthy controls throughout the cerebral cortex, limbic system, and basal ganglia. In addition, each of these psychiatric disorders exhibited a particular profile of neural features that ranged from disorder-specific, to category-specific, to transdiagnostic.
Conclusions
These findings indicate that psychiatric disorders exhibit a complex profile of neural features that vary in their disorder-specificity and can be detected with large-scale fMRI meta-analytic techniques. This approach has potential to fundamentally transform neuroimaging investigations of clinical disorders by providing a novel procedure for establishing disorder-specificity of observed results, which can be then used to advance our understanding of individual disorders as well as broader nosological issues related to diagnosis and classification of psychiatric disorders.
Generalized anxiety disorder (GAD) is a highly prevalent mental illness that is associated with clinically significant distress, functional impairment, and poor emotional regulation. Primary functional magnetic resonance imaging (fMRI) studies of GAD report neural abnormalities in comparison to healthy controls. However, many of these findings in the primary literature are inconsistent, and it is unclear whether they are specific to GAD or shared transdiagnostically across related disorders.
Objectives
This meta-analysis seeks to establish the most reliable neural abnormalities observed in individuals with GAD, as reported in the primary fMRI activation literature.
Methods
We conducted an exhaustive literature search in PubMed to identify primary studies that met our pre-specified inclusion criteria and then extracted relevant data from primary, whole-brain fMRI activation studies of GAD that reported coordinates in Talairach or MNI space. We then used multilevel kernel density analysis (MKDA) with ensemble thresholding to examine the differences between adults with GAD and healthy controls in order to identify brain regions that reached statistical significance across primary studies.
Results
Patients with GAD showed statistically significant (α=0.05–0.0001; family-wise-error-rate corrected) neural activation in various regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
These results inform our understanding of the neural basis of GAD and are interpreted using a frontolimbic model of anxiety as well as specific clinical symptoms of this disorder and its relation to other mood and anxiety disorders. These results also suggest possible novel targets for emerging neurostimulation therapies (e.g., transcranial magnetic stimulation) and may be used to advance our understanding of the effects of current pharmaceutical treatments and ways to improve treatment selection and symptom-targeting for patients diagnosed with GAD.