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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
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 field of Quaternary entomology has focused primarily on the study of beetles (Coleoptera) and, to a lesser degree, nonbiting midges (Diptera: Chironomidae). Beetles typically predominate because they have heavily sclerotised exoskeletons, and they are abundant in a great variety of habitats. Because of taphonomy and scarcity, other Quaternary invertebrates have been less studied. Only a few records of fleas (Siphonaptera) and mites (Acari) are reported from Pleistocene deposits that span the Seward Peninsula in Alaska, United States of America, to the Klondike goldfields in central Yukon Territory, Canada. Grasshoppers (Orthoptera) and thrips (Thysanoptera) have not been reported previously from Quaternary deposits across the Arctic’s Beringia region. However, recent extensive sampling of Arctic ground squirrel, Urocitellus parryii Richardson (Rodentia: Sciuridae), middens from permafrost deposits of the Klondike goldfields has yielded specimens from each of these underrepresented invertebrate groups. Here, we present records of fleas (Oropsylla alaskensis Baker (Ceratophyllidae)), mites (including Fusacarus Michael (Astigmata: Glycyphagidae) and cf. Haemogamasus Berlese (Mesostigmata: Laelapidae)), and the first records of grasshoppers (Acrididae: Gomphocerinae) and thrips (Thysanoptera: Thripidae) from Beringia from six middens spanning approximately 80 000–13 500 years BP. We also provide brief reviews of the fossil history of each major taxon.
Pragmatic trials aim to speed translation to practice by integrating study procedures in routine care settings. This study evaluated implementation outcomes related to clinician and patient recruitment and participation in a trial of community paramedicine (CP) and presents successes and challenges of maintaining pragmatic study features.
Methods:
Adults in the pre-hospital setting, emergency department (ED), or hospital being considered for referral to the ED/hospital or continued hospitalization for intermediate-level care were randomized 1:1 to CP care or usual care. Referral and enrollment data were tracked administratively, and patient characteristics were abstracted from the electronic health record (EHR). Enrolled patients completed baseline surveys, and a subset of intervention patients were interviewed. All CPs and a sample of clinicians and administrators were invited to complete a survey and interview.
Results:
Between January 2022 and February 2023, 240 enrolled patients (42% rural) completed surveys, and 22 completed an interview; 63 staff completed surveys and 20 completed an interview. Ninety-three clinicians in 27 departments made at least one referral. Factors related to referrals included program awareness and understanding the CP practice scope. Most patients were enrolled in the hospital, but characteristics were similar to the primary care population and included older and medically complex patients. Challenges to achieving representativeness included limited EHR infrastructure, constraints related to patient consenting, and clinician concerns about patient randomization disrupting preferred care.
Conclusion:
Future pragmatic trials in busy clinical settings may benefit from regulatory policies and EHR capabilities that allow for real-world study conduct and representative participation. Trial registration: NCT05232799.
Racially and ethnically minoritized populations have been historically excluded and underrepresented in research. This paper will describe best practices in multicultural and multilingual awareness-raising strategies used by the Recruitment Innovation Center to increase minoritized enrollment into clinical trials. The Passive Immunity Trial for Our Nation will be used as a primary example to highlight real-world application of these methods to raise awareness, engage community partners, and recruit diverse study participants.
As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring.
Methods:
The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed.
Results:
Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial’s DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report.
Conclusion:
It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.
Localized contamination from research-related activities and its effects on macrofauna communities in the marine environment were investigated at Palmer Station, a medium-sized Antarctic research station. Relatively low concentrations of polycyclic aromatic hydrocarbons (PAHs; 32–302 ng g-1) and total petroleum hydrocarbons (TPHs; 0.9–8.9 μg g-1) were detected in sediments adjacent to the sewage outfall and pier, where most human activities were expected to have occurred, and at even lower concentrations at two seemingly reference areas (PAHs 6–30 ng g-1, TPHs 0.03–5.1 μg g-1). Elevated concentrations of PAHs in one sample taken in one reference area (816 ng g-1) and polychlorinated biphenyls (353 ng g-1) and dichloro-diphenyl-trichloroethane (3.2 and 25.3 ng g-1) in two samples taken adjacent to the sewage outfall indicate spatial heterogeneity of localized sediment contamination. Limpet (Nacella concinna) tissues collected adjacent to Palmer Station had high concentrations of PAHs, copper, lead, zinc and several other metals relative to outlying islands. Sediment and limpet tissue contaminant concentrations have decreased since the early 1990s following the Bahía Paraíso spill. Natural sediment characteristics affected macrofaunal community composition more than contamination adjacent to Palmer Station, presumably because of the low overall contamination levels.
Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.
Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.
Methods
MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.
Results
VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.
Conclusions
Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.
The COVID-19 pandemic prompted the development and implementation of hundreds of clinical trials across the USA. The Trial Innovation Network (TIN), funded by the National Center for Advancing Translational Sciences, was an established clinical research network that pivoted to respond to the pandemic.
Methods:
The TIN’s three Trial Innovation Centers, Recruitment Innovation Center, and 66 Clinical and Translational Science Award Hub institutions, collaborated to adapt to the pandemic’s rapidly changing landscape, playing central roles in the planning and execution of pivotal studies addressing COVID-19. Our objective was to summarize the results of these collaborations and lessons learned.
Results:
The TIN provided 29 COVID-related consults between March 2020 and December 2020, including 6 trial participation expressions of interest and 8 community engagement studios from the Recruitment Innovation Center. Key lessons learned from these experiences include the benefits of leveraging an established infrastructure, innovations surrounding remote research activities, data harmonization and central safety reviews, and early community engagement and involvement.
Conclusions:
Our experience highlighted the benefits and challenges of a multi-institutional approach to clinical research during a pandemic.
A new optimized quasi-helically symmetric configuration is described that has the desirable properties of improved energetic particle confinement, reduced turbulent transport by three-dimensional shaping and non-resonant divertor capabilities. The configuration presented in this paper is explicitly optimized for quasi-helical symmetry, energetic particle confinement, neoclassical confinement and stability near the axis. Post optimization, the configuration was evaluated for its performance with regard to energetic particle transport, ideal magnetohydrodynamic stability at various values of plasma pressure and ion temperature gradient instability induced turbulent transport. The effects of discrete coils on various confinement figures of merit, including energetic particle confinement, are determined by generating single-filament coils for the configuration. Preliminary divertor analysis shows that coils can be created that do not interfere with expansion of the vessel volume near the regions of outgoing heat flux, thus demonstrating the possibility of operating a non-resonant divertor.
Owing to its high magnetic field, high power, and compact size, the SPARC experiment will operate with divertor conditions at or above those expected in reactor-class tokamaks. Power exhaust at this scale remains one of the key challenges for practical fusion energy. Based on empirical scalings, the peak unmitigated divertor parallel heat flux is projected to be greater than 10 GW m−2. This is nearly an order of magnitude higher than has been demonstrated to date. Furthermore, the divertor parallel Edge-Localized Mode (ELM) energy fluence projections (~11–34 MJ m−2) are comparable with those for ITER. However, the relatively short pulse length (~25 s pulse, with a ~10 s flat top) provides the opportunity to consider mitigation schemes unsuited to long-pulse devices including ITER and reactors. The baseline scenario for SPARC employs a ~1 Hz strike point sweep to spread the heat flux over a large divertor target surface area to keep tile surface temperatures within tolerable levels without the use of active divertor cooling systems. In addition, SPARC operation presents a unique opportunity to study divertor heat exhaust mitigation at reactor-level plasma densities and power fluxes. Not only will SPARC test the limits of current experimental scalings and serve for benchmarking theoretical models in reactor regimes, it is also being designed to enable the assessment of long-legged and X-point target advanced divertor magnetic configurations. Experimental results from SPARC will be crucial to reducing risk for a fusion pilot plant divertor design.
Current treatment approaches for depression center on various forms of psychosocial therapy and the use of antidepressant drugs. The response rates for both of these approaches are similar, with mostly reduction, but not complete remission, of symptoms. Poor adherence to recommended treatment is an issue complicating the management of depression and prevention of recurrent episodes. This study evaluated the efficacy of a novel form of receptive music therapy which can be easily adminstered to out patients.
Methods
Enrolled subjects (n=203, average age 49.6 ± 13.1 years, 28.1% male) were randomized into four arms: Music Therapy 1 (MT1), Music Therapy 2 (MT2), Placebo (nature sounds) and waiting-list Control. Subjects listened for 30 minutes, twice daily. Multivariate linear regression models assessed depressive symptom changes over five weeks, based on a composite scale (COMP) and the Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS-D) alone.
Results
On average, a significant, positive change in COMP was observed for MT1 (β=1.44, p=0.030), but not for MT2 (β=1.14, p=0.059) or Placebo (β=0.57, p=0.397). After 15 weeks, study participation was associated with a mean HAM-D score reduction of 60% for 89,1% of the compliant probands.
Conclusions
Newly composed receptive music therapy, as explored in this study, is associated with reduced depressive symptoms and high treatment compliance, and may therefore potentially represent an effective depression treatment alternative or adjunctive therapy to pharmacological and psychosocial approaches.
Depression is a prevalent, often chronic and disabling disease. Current psychosocial and antidepressant treatments result in similar response rates with mostly symptom reduction, but not complete remission. Poor treatment adherence complicates depression management and prevention of recurrent episodes. Therefore, new therapies must be developed urgently, that alone or combined with present treatments, can significantly improve therapy outcomes.
Depression is potentially associated with decreased heart rate variability (HRV). Based on our previous studies' results which demonstrated HRV increase following auditory stimulation, we developed two interventions based on specifically for depression treatment composed and arranged music and tested the efficacy in a waiting list and placebo controlled double-blind study with depressed outpatients.
Depression status was assessed at the beginning of T1 and T2 using the Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS-D) and by a composite (COMP) scale based on HAM-D, BDI and HADS-D z-scores. Changes in depressive symptoms between T1 and T2 (5 week period) were assessed based on COMP and on HAM-D, BDI and HADS-D scores alone. Compared to the control arm, a significant, positive effect in COMP was observed for MT1 at T2. Both MT1 and MT2 were associated with significant positive effects (HAM-D and HADS-D scores). MT2 resulted in positive effects on BDI scores. No significant change in any depression score was detected in the placebo arm. Treatment continuation was associated with an effect increase (mean HAM-D score reduction of 60%) after 10 to 15 weeks of treatment.
Patients diagnosed with glioblastoma (GBM) are treated with surgery followed by fractionated radiotherapy with concurrent and adjuvant temozolomide. Patients are monitored with serial magnetic resonance imaging (MRI). However, treatment-related changes frequently mimic disease progression. We reviewed a series of patients undergoing surgery for presumed first-recurrence GBM, where pathology reports were available for tissue diagnosis, in order to better understand factors associated with a diagnosis of treatment-related changes on final pathology.
Methods:
Patient records at a single institution between 2005 and 2015 were retrospectively reviewed. Pathology reports were reviewed to determine diagnosis of recurrent GBM or treatment effect. Survival analysis was performed interrogating overall survival (OS) and progression-free survival (PFS). Correlation with radiation treatment plans was also examined.
Results:
One-hundred-twenty-three patients were identified. One-hundred-sixteen patients (94%) underwent resection and seven underwent biopsy. Treatment-related changes were reported in 20 cases (16%). These patients had longer median OS and PFS from the time of recurrence than patients with true disease progression. However, there was no significant difference in OS from the time of initial diagnosis. Treatment effect was associated with surgery within 90 days of completing radiation. In patients receiving radiation at our institution (n = 53), larger radiation target volume and a higher maximum dose were associated with treatment effect.
Conclusion:
Treatment effect was associated with surgery nearer to completion of radiation, a larger radiation target volume, and a higher maximum point dose. Treatment effect was associated with longer PFS and OS from the time of recurrence, but not from the time of initial diagnosis.
The development of Middle Preclassic (900–300 BC) ceremonial architecture is receiving more attention by archaeologists conducting research in the Maya Lowlands. Although a few examples have been partially excavated, there is still a dearth of information on how and why monumental constructions were originally built. This is largely because early structures often lie below several layers of sequential architecture, making them difficult to locate. Even when Middle Preclassic architecture is identified, exposure is often too limited to fully investigate its form and function. A well-preserved and accessible Middle Preclassic platform would be a rare find and could greatly enhance our knowledge and understanding of the subject. At Pacbitun, Cayo District, Belize, such a discovery has been made beneath the artificially raised surface of the main plaza. To make the most of this opportunity, five seasons of excavation worked to expose this massive building in its entirety. In this article, we provide details concerning the structural design of the platform and its abandonment, as well as present potential architectural comparisons. We conclude by reevaluating complexity at Pacbitun.