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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.
To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individuals over time.
Methods
Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18–35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed.
Results
Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates.
Conclusions
Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.
Cardiac surgery-associated acute kidney injury (CS-AKI) and fluid overload (FO) are common among neonates who undergo cardiopulmonary bypass, and increase mortality risk. Current diagnostic criteria may delay diagnosis. Thus, there is a need to identify urine biomarkers that permit earlier and more accurate diagnosis.
Methods:
This single-centre ancillary prospective cohort study describes age- and disease-specific ranges of 14 urine biomarkers at perioperative time points and explores associations with CS-AKI and FO. Neonates (≤28 days) undergoing cardiac surgery were included. Preterm neonates or those who had pre-operative acute kidney injury were excluded. Urine biomarkers were measured pre-operatively, at 0 to < 8 hours after surgery, and at 8 to 24 hours after surgery. Exploratory outcomes included CS-AKI, defined by the modified Kidney Disease Improving Global Outcomes criteria, and>10% FO, both measured at 48 hours after surgery.
Results:
Overall, α-glutathione S-transferase, β-2 microglobulin, albumin, cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, uromodulin, clusterin, and vascular endothelial growth factor concentrations peaked in the early post-operative period; over the sampling period, kidney injury molecule-1 increased and trefoil factor-3 decreased. In the early post-operative period, β-2 microglobulin and α-glutathione S-transferase were higher in neonates who developed CS-AKI; and clusterin, cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, and α-glutathione S-transferase were higher in neonates who developed FO.
Conclusion:
In a small, single-centre cohort, age- and disease-specific urine biomarker concentrations are described. These data identify typical trends and will inform future studies.
Large datasets, combined with modeling techniques, provide a quantitative way to estimate when known archaeological sites will be impacted by climatological changes. With over 4,000 archaeological sites recorded on the coast of Georgia, USA, the state provides an ideal opportunity to compare methods. Here, we compare the popular passive “bathtub” modeling with the dynamic Sea Level Affecting Marshes Model (SLAMM) combined with the Marshes Equilibrium Model (MEM). The goal of this effort is to evaluate prior modeling and test the benefits of more detailed ecological modeling in assessing site loss. Our findings indicate that although rough counts of archaeological sites destroyed by sea-level rise (SLR) are similar in all approaches, using the latter two methods provides critical information needed in prioritizing site studies and documentation before irrevocable damages occur. Our results indicate that within the next 80 years, approximately 40% of Georgia's coastal sites will undergo a loss of archaeological context due to wetlands shifting from dry ecological zones to transitional marshlands or submerged estuaries and swamps.
The absorption of biologically important purines, pyrimidines, and nucleosides by Li-, Na-, Mg-, and Ca-montmorillonite has been studied in aqueous solutions over a range of pH values 2–12. The initial organic concentrations were about 1 m.molar. The ratio clay to organic compounds was such that only up to 25 per cent of the exchange capacity could be saturated by organic cations, but, depending on conditions, up to 100 per cent of the available organic material was absorbed. Of the nineteen compounds studied, only thymine, uracil, and their nucleosides were not absorbed under the experimental conditions. Absorption occurs primarily as a cation exchange reaction under acid conditions and varies with the basicity of the compounds, their aromatic or non-aromatic character, and the possible extent of their van der Waals interaction with the silicate layers. Nucleosides generally are less strongly absorbed than their purines or pyrimidines because their non-planar structure permits less van der Waals interaction; their absorption is influenced by the differences in swelling behavior of montmorillonite with mono- and divalent cations.
Absorptions of purine and pyrimidine derivatives by Co- and Ni- montmorillonite at pH < 6 and by Cu-montmorillonite at pH < 3 are similar to their absorption by Ca-montmorillonite and take place primarily by a cation exchange process. In the weakly acidic to weakly alkaline range, absorption is due to complex formation with the inorganic cations, and decrease in the order Cu ≫ Ni > Co ≫ Ca. Adenine, 7-methyladenine, hypoxanthine, and purine are strongly absorbed, 9-methyladenine, 6-chloropurine, and cytosine are weakly absorbed, and thymine and uracil are not absorbed. At pH < 5, the nucleosides are absorbed by Co-, Ni-, and Cu-montmorillonite in approximately the same manner as by Ca-montmorillonite, but at pH > 6 their absorptions decrease in the order Cu ≫ Ni > Co > Ca. Fe(III)-montmorillonite behaves quite differently from the other mont-morillonites studied. With purines and pyrimidines, there is strong absorption from pH 3 to pH 7–8; with the nucleosides, the absorption varies considerably with the compounds considered decreasing in the order adenosine > cytidine ≫ guanosine ≫ inosine.
Quantitative analysis of clay minerals by X-ray powder diffraction requires oriented clays in order to increase detection limits of the analyses. This is achieved commonly either by smear or sedimentation techniques; however, these techniques can lead to poor analytical precision when used with an internal standard because they often produce non-homogeneous internal standard—clay mineral mixtures. Compaction of bulk shale material at 8000 psi in an hydraulic press produces preferred orientations comparable to that produced by smear or sedimentation. When used with a suitable platy internal standard which provides an estimate of clay mineral preferred orientation, excellent analytical precision is achieved routinely. Several lines of experimental evidence indicate that 1–5 µm MoS2 is an ideal orienting internal standard for use with compaction mounts.
Bulk and size-fractionated kaolinites from seven localities in Australia as well as the Clay Minerals Society Source Clays Georgia KGa-1 and KGa-2 have been studied by X-ray diffraction (XRD), laser scattering, and electron microscopy in order to understand the variation of particle characteristics across a range of environments and to correlate specific particle characteristics with intercalation behavior. All kaolinites have been intercalated with N-methyl (NMF) after pretreatment with hydrazine hydrate, and the relative efficiency of intercalation has been determined using XRD. Intercalate yields of kaolinite: NMF are consistently low for bulk samples that have a high proportion of small-sized particles (i.e., <0.5 µm) and for biphased kaolinites with a high percentage (>60%) of low-defect phase. In general, particle size appears to be a more significant controlling factor than defect distribution in determining the relative yield of kaolinite: NMF intercalate.
Kaolinite:NaCl intercalates with basal layer dimensions of 0.95 and 1.25 nm have been prepared by direct reaction of saturated aqueous NaCl solution with well-crystallized source clay KGa-1. The intercalates and their thermal decomposition products have been studied by XRD, solid-state 23Na, 27Al, and 29Si MAS NMR, and FTIR. Intercalate yield is enhanced by dry grinding of kaolinite with NaCl prior to intercalation. The layered structure survives dehydroxylation of the kaolinite at 500°–600°C and persists to above 800°C with a resultant tetrahedral aluminosilicate framework. Excess NaCl can be readily removed by rinsing with water, producing an XRD “amorphous” material. Upon heating at 900°C this material converts to a well-crystallized framework aluminosilicate closely related to low-carnegieite, NaAlSiO4, some 350°C below its stability field. Reaction mechanisms are discussed and structural models proposed for each of these novel materials.
Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I–III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30–60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.
Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population.
Aims
To investigate whether omega-3 polyunsaturated fatty acid (n−3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis.
Method
Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n−3 PUFA levels predicted change in cognitive performance.
Results
The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months.
Conclusions
We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n−3 PUFAs.
The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.
Method
Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.
Results
Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.
Conclusions
We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
In March 2020, New York City became the epicenter of the coronavirus disease 2019 (COVID-19) pandemic in the United States. Because healthcare facilities were overwhelmed with patients, the Jacob K. Javits Convention Center was transformed into the nation’s largest alternate care site: Javits New York Medical Station (hereafter termed Javits). Protecting healthcare workers (HCWs) during a global shortage of personal protective equipment (PPE) in a nontraditional healthcare setting posed unique challenges. We describe components of the HCW safety program implemented at Javits.
Setting:
Javits, a large convention center transformed into a field hospital, with clinical staff from the US Public Health Service Commissioned Corps and the US Department of Defense.
Methods:
Key strategies to ensure HCW safety included ensuring 1-way flow of traffic on and off the patient floor, developing a matrix detailing PPE required for each work activity and location, PPE extended use and reuse protocols, personnel training, and monitoring adherence to PPE donning/doffing protocols when entering or exiting the patient floor. Javits staff who reported COVID-19 symptoms were immediately isolated, monitored, and offered a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction (RT-PCR) test.
Conclusions:
A well-designed and implemented HCW safety plan can minimize the risk of SARS-CoV-2 infection for HCWs. The lessons learned from operating the nation’s largest COVID-19 alternate care site can be adapted to other environments during public health emergencies.
The utility of questionnaire based self-report measures for non-clinical psychotic symptoms is unclear and there are few reliable data about the nature and prevalence of these phenomena in children. The study aimed to investigate psychosis-like symptoms (PLIKS) in children utilizing both self-report measures and semi-structured observer rated assessments.
Methods:
The study was cross-sectional; the setting being an assessment clinic for members of the ALSPAC birth cohort in Bristol, UK. 6455 respondents were assessed over 21 months, mean age 12.9 years. The main outcome measure was: 12 self-report screening questions for psychotic symptoms followed by semi-structured observer rated assessments by trained psychology graduates. The assessment instrument utilised stem questions, glossary definitions, and rating rules adapted from DISC-IV and SCAN items.
Results:
The 6-month period prevalence for one or more PLIKS rated by self-report questions was 38.9 % (95% CI = 37.7-40.1). Prevalence using observer rated assessments was 13.7% (95% CI = 12.8-14.5). Positive Predictive Values for the screen questions versus observer rated scores were low, except for auditory hallucinations (PPV=70%; 95% CI = 67.1-74.2). The most frequent observer rated symptom was auditory hallucinations (7.3%); in 18.8% of these cases symptoms occurred weekly or more. The prevalence of DSM-IV ‘core’ schizophrenia symptoms was 3.62%. Rates were significantly higher in children with low socio-economic status.
Conclusions:
With the exception of auditory hallucinations, self-rated questionnaires are likely to substantially over-estimate the frequency of PLIKS in 12-year-old children. However, more reliable observer rated assessments reveal that PLIKS occur in a significant proportion of children.
We sampled individual growth rings from three ancient remnant bald cypress (Taxodium distichum) trees from a massive buried deposit at the mouth of the Altamaha River on the Georgia Coast to determine the best technique for radiocarbon (14C) dating pretreatment. The results of our comparison of traditional ABA pretreatment and holocellulose and α-cellulose fractions show no significant differences among the pretreatments (<1 sigma) thereby suggesting that ABA pretreatment will prove sufficient for the development of a high-resolution 14C tree-ring chronology based on these ancient bald cypresses which will indicate whether the U.S. Southeast is subject to a regional radiocarbon offset.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350 $\mu$m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200 $\mu$m images will also have a factor $\sim $30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.