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Adverse childhood experiences (ACEs) are associated with physical and mental health difficulties in adulthood. This study examines the associations of ACEs with functional impairment and life stress among military personnel, a population disproportionately affected by ACEs. We also evaluate the extent to which the associations of ACEs with functional outcomes are mediated through internalizing and externalizing disorders.
Methods
The sample included 4,666 STARRS Longitudinal Study (STARRS-LS) participants who provided information about ACEs upon enlistment in the US Army (2011–2012). Mental disorders were assessed in wave 1 (LS1; 2016–2018), and functional impairment and life stress were evaluated in wave 2 (LS2; 2018–2019) of STARRS-LS. Mediation analyses estimated the indirect associations of ACEs with physical health-related impairment, emotional health-related impairment, financial stress, and overall life stress at LS2 through internalizing and externalizing disorders at LS1.
Results
ACEs had significant indirect effects via mental disorders on all functional impairment and life stress outcomes, with internalizing disorders displaying stronger mediating effects than externalizing disorders (explaining 31–92% vs 5–15% of the total effects of ACEs, respectively). Additionally, ACEs exhibited significant direct effects on emotional health-related impairment, financial stress, and overall life stress, implying ACEs are also associated with these longer-term outcomes via alternative pathways.
Conclusions
This study indicates ACEs are linked to functional impairment and life stress among military personnel in part because of associated risks of mental disorders, particularly internalizing disorders. Consideration of ACEs should be incorporated into interventions to promote psychosocial functioning and resilience among military personnel.
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.
Background: Brain-specific glial fibrillary acidic protein (GFAP) can discriminate stroke type [ischemic stroke (AIS), intracerebral hemorrhage (ICH), stroke mimics (SM)]. Novel point-of-care technology (GFAP levels <15 minutes) is a promising diagnostic tool. We aim to evaluate the feasibility of rapid GFAP analysis in acute stroke. Methods: Exploratory analysis of an ongoing prospective study of suspected undifferentiated stroke <24h from onset. Rapid plasma GFAP levels (pg/mL) are measured at hospital arrival using the i-STAT Alinity® instrument and commercially-available cartridges. Study endpoints include quantitative GFAP levels according to final diagnosis and time from stroke onset. Results: Among 200 patients (mean(±SD) 70.7±15.5 years, 44.5% female, median (IQR) NIHSS 9(4-19), diagnosis was AIS (n=132 (59 large-vessel occlusion), ICH (n=17), and SM (n=51). Median time from hospital arrival to GFAP result was 56.0 (47.0-69.5) minutes. Median rapid GFAP levels were highest in ICH (878.0 (70.5-3,906.5) pg/mL) compared to AIS (49.5 (29.0-95)pg/mL) and SM (29(29-64)pg/mL), p=0.001. Median GFAP was higher in AIS-known onset >4.5h (n=9) (110.0 (44.0-216.0) pg/mL) compared to AIS<4.5h (40.5 (29.0-68.8) pg/mL) (n=72), (p=0.047), while AIS-unknown onset (n=51) (68.0 (29.0-108.5) pg/mL) fell between these two groups, likely reflecting the subgroup’s heterogeneity. Conclusions: Preliminary findings suggest that rapid GFAP analysis is feasible in acute stroke and may inform treatment decisions.
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.
Grazing is a crucial component of dairy farms across many regions of the world. This review explores challenges related to grazing infrastructure and opportunities for future improvement. Farmers who aim to increase pasture utilisation face heightened inter-animal competition necessitated by pasture restriction to achieve target post-grazing sward heights. Increasing the frequency of fresh pasture allocation beyond once per day has been observed to reduce milk production in primiparous animals, due to intensified competition for limited feed resources. Implementing grazing paddocks tailored for 24- to 36-hour allocations helps to mitigate inter-animal competition while concurrently preventing the grazing of fresh regrowth. Crucial to this approach is establishing farm roadway infrastructure that allows access to all sections of the grazing platform. However, the development of these roadway networks has often occurred without a comprehensive assessment of their impact on the efficiency of the dairy herd’s movement between grazing paddocks and the milking parlour. The efficiency of the dairy herd’s movement is most significantly influenced by the location of the milking parlour within the grazing platform. Extreme walking distances or challenging terrain on farm roadways may have an impact on milk production per cow. Factors such as farm roadway surface quality and width significantly influence cow throughput on farm roadways. Recent studies have highlighted inadequate roadway widths on many farms relative to their herd size, while surface condition may also be limiting cow throughput on these farms. Enhancing roadway width and surface condition of farm roadways may improve labour efficiency on commercial farms.
In 2015, a continuous 15.4 m snow/firn core was recovered from central South Georgia Island at ∼850 m a.s.l. All firn core samples were analyzed for major (Al, Ca, Mg, Na, K, Ti and Fe) and trace element concentrations (Sr, Cd, Cs, Ba, La, Ce, Pr, Pb, Bi, U, As, Li, S, V, Cr, Mn, Co, Cu and Zn) and stable water isotopes. The chemical and isotopic signal is well preserved in the top 6.2 m of the core. Below this depth, down to the bottom of the core, signal dampening is observed in the majority of the elemental species making it difficult to distinguish a seasonal signal. Thirteen elements (As, Bi, Ca, Cd, Cu, K, Li, Mg, Na, Pb, S, Sr and Zn) have crustal enrichment factor values higher than 10 suggesting sources in addition to those found naturally in the crust. While this study shows that 850 m a.s.l. is not high enough to preserve a record including recent years, higher-elevation (>1250 m a.s.l.) glaciers may be likely candidates for ice core drilling to recover better-preserved, continuous, recent to past glaciochemical records.
Recent theories have implicated inflammatory biology in the development of psychopathology and maladaptive behaviors in adolescence, including suicidal thoughts and behaviors (STB). Examining specific biological markers related to inflammation is thus warranted to better understand risk for STB in adolescents, for whom suicide is a leading cause of death.
Method:
Participants were 211 adolescent females (ages 9–14 years; Mage = 11.8 years, SD = 1.8 years) at increased risk for STB. This study examined the prospective association between basal levels of inflammatory gene expression (average of 15 proinflammatory mRNA transcripts) and subsequent risk for suicidal ideation and suicidal behavior over a 12-month follow-up period.
Results:
Controlling for past levels of STB, greater proinflammatory gene expression was associated with prospective risk for STB in these youth. Similar effects were observed for CD14 mRNA level, a marker of monocyte abundance within the blood sample. Sensitivity analyses controlling for other relevant covariates, including history of trauma, depressive symptoms, and STB prior to data collection, yielded similar patterns of results.
Conclusions:
Upregulated inflammatory signaling in the immune system is prospectively associated with STB among at-risk adolescent females, even after controlling for history of trauma, depressive symptoms, and STB prior to data collection. Additional research is needed to identify the sources of inflammatory up-regulation in adolescents (e.g., stress psychobiology, physiological development, microbial exposures) and strategies for mitigating such effects to reduce STB.
Highly portable and accessible MRI technology will allow researchers to conduct field-based MRI research in community settings. Previous guidance for researchers working with fixed MRI does not address the novel ethical, legal, and societal issues (ELSI) of portable MRI (pMRI). Our interdisciplinary Working Group (WG) previously identified 15 core ELSI challenges associated with pMRI research and recommended solutions. In this article, we distill those detailed recommendations into a Portable MRI Research ELSI Checklist that offers practical operational guidance for researchers contemplating using this technology.
Historical changes from shifting land use, the natural meandering of waterways, and the aftereffects of erosion complicate modern environments and obfuscate precontact landscapes. Although archaeologists can create stratified sampling models or employ systematic surveys, traditional field methodologies are often not suitable for site discovery, thereby limiting knowledge of ancient cultural landscapes. Many water systems in southern Louisiana, and in many parts of the world, have been covered or concealed in backswamps by natural geomorphological processes, development, or environmental degradation. Investigation standards that do not account for these changes will not be effective at identifying archaeological sites in such transformed landscapes. Discoveries made during ongoing archaeological research in Iberville Parish, Louisiana, provide examples of what can be missed and offer solutions through changes in archaeological field methods. This article advocates for a mixed-methodology approach, drawing from historical research and shallow geophysics to look at landforms and landscape changes. Strictly following state survey guidelines can muddle the archaeological record, particularly in places subject to significant landscape change from historical land-use alteration. By applying these approaches, we offer a way to reconstruct ancient landscapes and landforms that are culturally significant but often missed given the nature of modern environmental conditions.
The negative predictive value of blaCTX-M on BCID2 for ceftriaxone resistance in E. coli and K. pneumoniae group was 97% and 94%, respectively. Creation of a genotypic antibiogram led to updated local guidance for clinicians to utilize for empiric treatment of Enterobacterales bloodstream infections identified via rapid diagnostics.
Congenital coronary artery stenosis coexisting with aortic coarctation in nonsyndromic patients has not previously been reported. This report describes a nonsyndromic aortic coarctation patient who experienced intraoperative cardiac arrest due to a previously undiagnosed critical left main coronary artery stenosis. The patient was successfully resuscitated, underwent patch coronary ostioplasty, and was discharged home. He remains well for four months following repair.
Background: Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogenous group of disorders with the common theme of iron accumulation in the basal ganglia. These disorders typically present in childhood with progressive neurodegeneration and neuropsychiatric symptoms. Caring for an individual with NBIAs is intensive, however it is unknown what factors impact caregiver well-being and quality of life. Methods: Common themes were obtained via literature review of quality of life surveys in children with neurological and chronic illnesses. Five domains were addressed: Diagnosis, Communication, Symptom Management, Clinical Experience and Resources/Support. The survey was approved by the Family Advisory Committee at the CHEO Research Institute and the CHEO REB. The survey was distributed via the Rare Connect Platform to Canadian caregivers. Results: Survey responses are being analyzed and will be presented at the CNSF. Within each domain, Likert scales will be analyzed. Domains will be ranked according to the caregiver responses. Conclusions: Results of this survey will assist in developing care management guidelines, resources for families and help with future advocacy for patients and families affected by NBIAs. The results will also help guide future NBIA Canada Family Conferences.
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
Methods
As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
Results
Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
Conclusions
Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
Illite diagenesis in Tertiary and Mesozoic shales in the Bergen High area, northern North Sea, was studied using mineralogic, isotopic, and computerized thermal modeling techniques. The Tertiary shales are dominated by smectite, with lesser amounts of illite, kaolinite, and chlorite. At present burial temperatures of >70°C smectite is absent, and the shales contain abundant lath-shaped illite which yields a mixed-layer illite/smectite (I/S) X-ray powder diffraction (XRD) pattern. Transmission electron microscopy (TEM) indicates that the illite laths increase in abundance and thickness with increasing depth; XRD patterns indicate a progressive increase in the illite component of the I/S. The deepest samples were found to contain long-range ordered (R=3) I/S, which showed platy particle morphology with the TEM. K-Ar ages of most of the <0.1-μm-size illite separates imply that illitization was a relatively brief event affecting a thick sequence of sediments during late Cretaceous to early Paleocene time (65–87 Ma); however, measured ages were affected by trace levels of detrital Ar contamination and do not represent the true age of diagenesis.
Several methods of quantifying Ar contamination were used to correct measured ages to obtain a reasonable estimate of the true age of diagenesis. The corrected ages are imprecise due to uncertainties in quantifying the levels of sample contamination, but generally suggest a Paleogene (38–66 Ma) period of illitization. In contrast, simple kinetic models of smectite-illitization suggest much younger ages of diagenesis (0–40 Ma at the Veslefrikk field; 0–60 Ma at the Huldra field). The timing of the diagenesis and the morphologic aspects of the authigenic illite suggest that illite precipitated before late Tertiary compaction and resulted in a decrease in fluid permeability. Low trapping efficiency of early Tertiary sediments, vertical escape of warm fluid from the Brent sandstone, and high heat flow may have promoted illite diagenesis in the shales prior to deep late-Tertiary burial.
Evaluation of adult antibiotic order sets (AOSs) on antibiotic stewardship metrics has been limited. The primary outcome was to evaluate the standardized antimicrobial administration ratio (SAAR). Secondary outcomes included antibiotic days of therapy (DOT) per 1,000 patient days (PD); selected antibiotic use; AOS utilization; Clostridioides difficile infection (CDI) cases; and clinicians’ perceptions of the AOS via a survey following the final study phase.
Design:
This 5-year, single-center, quasi-experimental study comprised 5 phases from 2017 to 2022 over 10-month periods between August 1 and May 31.
Setting:
The study was conducted in a 752-bed tertiary care, academic medical center.
Intervention:
Our institution implemented AOSs in the electronic medical record (EMR) for common infections among hospitalized adults.
Results:
For the primary outcome, a statistically significant decreases in SAAR were detected from phase 1 to phase 5 (1.0 vs 0.90; P < .001). A statistically significant decreases were detected in DOT per 1,000 PD (4,884 vs 3,939; P = .001), fluoroquinolone orders (407 vs 175; P < .001), carbapenem orders (147 vs 106; P = .024), and clindamycin orders (113 vs 73; P = .01). No statistically significant change in mean vancomycin orders was detected (991 vs 902; P = .221). A statistically significant decrease in CDI cases was also detected (7.8, vs 2.4; P = .002) but may have been attributable to changes in CDI case diagnosis. Clinicians indicated that the AOSs were easy to use overall and that they helped them select the appropriate antibiotics.
Conclusions:
Implementing AOS into the EMR was associated with a statistically significant reduction in SAAR, antibiotic DOT per 1,000 PD, selected antibiotic orders, and CDI cases.
The Eocene Huber Formation, exposed in the CFI Hall mine south of Irwinton, in Wilkinson County, Georgia, displays colored zones that are a consequence of an oxidative weathering front. These zones vary from very light gray (gray) to pinkish white (pink) to very pale yellow (cream) (Munsell N8, 5YR 8/2 and 2.5Y 8/2, respectively) with increasing degree of oxidation. A representative sample from each zone was collected and analyzed for its chemical, crystallographic and Raman spectroscopic properties. The comparison of these genetically related samples allowed for a quantitatively accurate assessment of anatase’s contribution to the total TiO2 content. All samples contain ∼1.5 wt.% TiO2. Progressing from gray to pink to cream, anatase contents range from half to nearly all the TiO2. The a lattice parameter for anatase is constant in all three kaolins (3.7916 Å), suggesting a constant 4.6 mol.% isomorphous substitution of Fe for Ti.
Phase characterization and mass-balance considerations of the gray, pink and cream kaolins indicate that ilmenite and pyrite are precursor Ti- and Fe-bearing phases in the gray kaolin that undergo oxidation. Pseudorutile is a proposed intermediate phase resulting from the anodic corrosion of ilmenite. Hematite, goethite and anatase are the dominant end-products via dissolution-precipitation from the reactants pyrite and pseudorutile. The removal of Fe sulfides and organic matter and addition of hematite and goethite causes kaolin colors to change from gray to pink. Oxygen diffusing from groundwater in permeable overlying and underlying formations facilitates a process that probably involves aerobic and anaerobic bacteria that utilize Fe from pyrite, hematite and goethite. We postulate that the end result is the mobilization of Fe by siderophores and a kaolin color change from pink to cream.
Strong gas-mineral interactions or slow adsorption kinetics require a molecular-level understanding of both adsorption and diffusion for these interactions to be properly described in transport models. In this combined molecular simulation and experimental study, noble gas adsorption and mobility is investigated in two naturally abundant zeolites whose pores are similar in size (clinoptilolite) and greater than (mordenite) the gas diameters. Simulated adsorption isotherms obtained from grand canonical Monte Carlo simulations indicate that both zeolites can accommodate even the largest gas (Rn). However, gas mobility in clinoptilolite is significantly hindered at pore-limiting window sites, as seen from molecular dynamics simulations in both bulk and slab zeolite models. Experimental gas adsorption isotherms for clinoptilolite confirm the presence of a kinetic barrier to Xe uptake, resulting in the unusual property of reverse Kr/Xe selectivity. Finally, a kinetic model is used to fit the simulated gas loading profiles, allowing a comparison of trends in gas diffusivity in the zeolite pores.
Cognitive decline is a common non-motor feature of Parkinson's disease (PD). However, the underlying mechanisms of cognitive impairment in PD require further elucidation. FDG PET imaging data analyses have revealed distinct brain metabolic patterns associated with the cognitive features of PD. The PD cognition-related pattern (PDCP) and default mode network (DMN) are two overlapping, but topographically distinct, networks that may serve as biomarkers of cognitive decline in PD. Decreased activity of the resting-state DMN and increased expression of the PDCP are associated with cognitive impairment in PD. Studies have consistently demonstrated the association between neuropsychological memory test performance and PDCP expression. Thus, we examined whether memory performance could offer additional value in predicting PDCP expression in PD patients. We hypothesized that DMN and memory performance would predict greater variance in PDCP expression than the DMN alone.
Participants and Methods:
Participants included 48 PD patients ages 46-80 (mean (SD) Age: 61.9 (8.1), Education: 15.0 (2.8), IQ: 112.5 (14.9), DRS total: 136.7 (5.8)). All participants completed the FDG PET and neuropsychological evaluation 8-12 hours after their last dose of Levodopa. Neuropsychological memory testing included the California Verbal Learning Test (CVLT) z score of sum of learning trials. PDCP and DMN values were z scores generated from normal controls in previous studies. Data were analyzed using linear regression analyses.
Results:
A hierarchical regression was performed to predict PDCP as a function of DMN and CVLT learning performance. Variables were entered in two separate blocks. The first block included DMN as a predictor, and the overall regression was significant (R2 = 0.55, F(1, 39)= 47.0, p < 0.001). As hypothesized, DMN significantly predicted PCDP expression (β= -0.74, p < 0.001). The second block of the regression included CVLT learning memory performance. Both DMN and CVLT performance explained a significant amount of variance in PDCP (R2 change = 0.05, F(2, 39)= 27.6, p < 0.001). CVLT performance significantly predicted PDCP (β= -0.22, p =0.048). The final model accounted for 60.0% of the variance inPDCP.
Conclusions:
Disruptions in functional connectivity within brain networks have become increasingly recognized as mechanisms responsible for cognitive impairment in patients. As demonstrated in previous studies, our results indicated that DMN loss is a strong predictor of PDCP expression, likely due to the networks' overlapping spatial regions. However, we found that the addition of memory performance to the model could explain a small amount of variance (5%) over and above DMN expression. Overall, the current findings demonstrate a functional (i.e., learning) distinction between population-specific (PDCP) and more general brain networks (DMN).