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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.
Along with increasing product complexity and quality requirements, the consistent consideration of inevitable production-induced variations within the product development process becomes a decisive factor for the market success of products. Consequently, various tolerancing approaches have emerged over the last few decades. However, tolerancing is considered complex in education, research, and industry, as it is a highly interdisciplinary task that takes place at different levels of detail, ranging from Robust Design to tolerance specification to manufacturing process design. This contribution proposes a novel approach that allows a holistic and structured description of tolerancing and fosters a common understanding among all involved stakeholders from design, manufacturing, and inspection. This is achieved by categorizing it into several distinct elements: activities, methods, tools, models and data, information, and knowledge. This ensures clarity and supports the utilization of existing approaches. While this contribution focuses on tolerancing in product design, the linkage to subsequent product realization stages and further engineering domains is also addressed in the proposed description scheme. An exemplary classification of research papers and a description of a practical development process of a technical system with its different tolerancing activities illustrate the benefits of the proposed description scheme.
Humanitarian mine action (HMA) stakeholders have an organized presence with well-resourced medical capability in many conflict and post-conflict settings. Humanitarian mine action has the potential to positively augment local trauma care capacity for civilian casualties of explosive ordnance (EO) and explosive weapons (EWs). Yet at present, few strategies exist for coordinated engagement between HMA and the health sector to support emergency care system strengthening to improve outcomes among EO/EW casualties.
Methods:
A scoping literature review was conducted to identify records that described trauma care interventions pertinent to civilian casualties of EO/EW in resource-constrained settings using structured searches of indexed databases and grey literature. A 2017 World Health Organization (WHO) review on trauma systems components in low- and middle-income countries (LMICs) was updated with additional eligible reports describing trauma care interventions in LMICs or among civilian casualties of EO/EWs after 2001.
Results:
A total of 14,195 non-duplicative records were retrieved, of which 48 reports met eligibility criteria. Seventy-four reports from the 2017 WHO review and 16 reports identified from reference lists yielded 138 reports describing interventions in 47 countries. Intervention efficacy was assessed using heterogenous measures ranging from trainee satisfaction to patient outcomes; only 39 reported mortality differences. Interventions that could feasibly be supported by HMA stakeholders were synthesized into a bundle of opportunities for HMA engagement designated links in a Civilian Casualty Care Chain (C-CCC).
Conclusions:
This review identified trauma care interventions with the potential to reduce mortality and disability among civilian EO/EW casualties that could be feasibly supported by HMA stakeholders. In partnership with local and multi-lateral health authorities, HMA can leverage their medical capabilities and expertise to strengthen emergency care capacity to improve trauma outcomes in settings affected by EO/EWs.
Cells of magnetotactic bacteria are used as model systems for studying the magnetic properties of ferrimagnetic nanocrystals. Each individual bacterial strain produces magnetosomes (membrane-bounded magnetic crystals) that have distinct sizes, shapes, crystallographic orientations and spatial arrangements, thereby providing nanoparticle systems whose unique magnetic properties are unmatched by synthetic chemically-produced crystals. Here, we use off-axis electron holography in the transmission electron microscope to study the magnetic properties of isolated and closely-spaced bullet-shaped magnetite (Fe3O4) magnetosomes biomineralized by the following magnetotactic bacterial strains: the cultured Desulfovibrio magneticus RS-1 and the uncultured strains LO-1 and HSMV-1. These bacteria biomineralize magnetite crystals whose crystallographic axes of elongation are parallel to <100> (RS-1 and LO-1) or <110> (HSMV-1). We show that the individual magnetosome crystals are single magnetic domains and measure their projected in-plane magnetization distributions and magnetic dipole moments. We use analytical modelling to assess the interplay between shape anisotropy and the magnetically preferred <111> magneto-crystalline easy axis of magnetite.
The early use of Robust Design (RD) supports the development of product concepts with low sensitivity to variation, which offers advantages for reducing the risk of costly iterations. Due to the lack of approaches for early evaluation of product robustness, the embodiment-function-relation and tolerance (EFRT-) model was developed, which combines the contact and channel approach and tolerance graphs. The information exchange of both approaches offers a high potential for reliable robustness evaluation results. However, that potential currently relies unused, since the link between applicable robustness criteria and the extended information is missing. To solve this problem, four research steps were determined: (1) understanding of robustness, (2) collection of RD principles, (3) identification of EFRT-model information and (4) mapping of RD principles and information. The results show nine adapted RD principles, the identified model information for the robustness evaluation, the evaluation criteria as well as their mapping. Utilizing the mapping and the proposed criteria in this contribution, a more comprehensive robustness evaluation in early stages is enabled.
To investigate the effect of body mass index on hearing outcomes, operative time and complication rates following stapes surgery.
Method
This is a five-year retrospective review of 402 charts from a single tertiary otology referral centre from 2015 to 2020.
Results
When the patient's shoulder was adjacent to the surgeon's dominant hand, the average operative time of 40 minutes increased to 70 minutes because of a significant positive association between higher body mass index and longer operative times (normal body mass index group (<25 kg/m2) r = 0.273, p = 0.032; overweight body mass index group (25–30 kg/m2) r = 0.265, p = 0.019). Operative times were not significantly longer upon comparison of low and high body mass index groups without stratification by laterality (54.9 ± 19.6 minutes vs 57.8 ± 19.2 minutes, p = 0.127).
Conclusion
There is a clinically significant relationship between body mass index and operating times. This may be due to access limitations imposed by shoulder size.
The mathematical physicists Bershadsky–Cecotti–Ooguri–Vafa (BCOV) proposed, in a seminal article from 1994, a conjecture extending genus zero mirror symmetry to higher genera. With a view towards a refined formulation of the Grothendieck–Riemann–Roch theorem, we offer a mathematical description of the BCOV conjecture at genus one. As an application of the arithmetic Riemann–Roch theorem of Gillet–Soulé and our previous results on the BCOV invariant, we establish this conjecture for Calabi–Yau hypersurfaces in projective spaces. Our contribution takes place on the B-side, and together with the work of Zinger on the A-side, it provides the first complete examples of the mirror symmetry program in higher dimensions. The case of quintic threefolds was studied by Fang–Lu–Yoshikawa. Our approach also lends itself to arithmetic considerations of the BCOV invariant, and we study a Chowla–Selberg type theorem expressing it in terms of special $\Gamma $-values for certain Calabi–Yau manifolds with complex multiplication.
Immigrants now constitute a sizeable and rapidly growing group among many Western countries' electorates, but analyses of their party preferences remain limited. Theoretically, immigrants' party preferences might be explained with both standard electoral theories and immigrant-specific approaches. In this article, we rigorously test both perspectives against each other using the most recent data from Germany. Applying the Michigan model, with its three central explanatory variables – party identification, issue orientations and candidate evaluations – to the party preferences of immigrant-origin and native voters, we find that this standard model can explain both groups well. In contrast, we find no direct effects of the most prominent immigrant-specific variables, and neither do these meaningfully moderate the Michigan variables. However, we find strong formative effects on the presence of political attitudes and beliefs: immigrants with a longer time spent in Germany, a stronger German identity and less experience of discrimination report significantly fewer item non-responses for the Michigan model's main explanatory variables.
The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.
Targeted drug development efforts in patients with CHD are needed to standardise care, improve outcomes, and limit adverse events in the post-operative period. To identify major gaps in knowledge that can be addressed by drug development efforts and provide a rationale for current clinical practice, this review evaluates the evidence behind the most common medication classes used in the post-operative care of children with CHD undergoing cardiac surgery with cardiopulmonary bypass.
Methods:
We systematically searched PubMed and EMBASE from 2000 to 2019 using a controlled vocabulary and keywords related to diuretics, vasoactives, sedatives, analgesics, pulmonary vasodilators, coagulation system medications, antiarrhythmics, steroids, and other endocrine drugs. We included studies of drugs given post-operatively to children with CHD undergoing repair or palliation with cardiopulmonary bypass.
Results:
We identified a total of 127 studies with 51,573 total children across medication classes. Most studies were retrospective cohorts at single centres. There is significant age- and disease-related variability in drug disposition, efficacy, and safety.
Conclusion:
In this study, we discovered major gaps in knowledge for each medication class and identified areas for future research. Advances in data collection through electronic health records, novel trial methods, and collaboration can aid drug development efforts in standardising care, improving outcomes, and limiting adverse events in the post-operative period.
Although cardiac catheterisation (cath) is the diagnostic test for pulmonary hypertension, it is an invasive procedure. Echocardiography (echo) is commonly used for the non-invasive diagnosis of pulmonary hypertension but maybe limited by lack of adequate signals. Therefore, emphasis has been placed on biomarkers as a potential diagnostic tool. No prior paediatric studies have simultaneously compared N-terminal pro-B-type-natriuretic peptide (NTproBNP) with cath/echo as a potential diagnostic tool. The aim of this study was to determine if NTproBNP was a reliable diagnostic tool for pulmonary hypertension in this population.
Methods:
Patients were divided into Study (echo evidence/established diagnosis of pulmonary hypertension undergoing cath) and Control (cath for small atrial septal defect/patent ductus arteriosus and endomyocardial biopsy post cardiac transplant) groups. NTproBNP, cath/echo data were obtained.
Results:
Thirty-one patients met inclusion criteria (10 Study, 21 Control). Median NTproBNP was significantly higher in the Study group. Echo parameters including transannular plane systolic excursion z scores, pulmonary artery acceleration time and right ventricular fractional area change were lower in the Study group and correlated negatively with NTproBNP. Receiver operation characteristic curve analysis demonstrated NTproBNP > 389 pg/ml was 87% specific for the diagnosis of pulmonary hypertension with the addition of pulmonary artery acceleration time improving the specificity.
Conclusions:
NTproBNP may be a valuable adjunctive diagnostic tool for pulmonary hypertension in the paediatric population. Echo measures of transannular plane systolic excursion z score, pulmonary artery acceleration time and right ventricular fractional area change had negative correlations with NTproBNP. The utility of NTproBNP as a screening tool for pulmonary hypertension requires validation in a population with unknown pulmonary hypertension status.
We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19) was <0.5%, which suggests that early local public health interventions were successful. Although our protocol was resource intensive, it prevented exposures to healthcare team members.
Greenhouse and outdoor container experiments were conducted to determine garden spurge and large crabgrass emergence when seeds were placed either on top of or below three different mulch materials [pine bark (PB), hardwood (HW), or pine straw (PS)] applied at five depths (0, 1.3, 2.5, 5.1, and 10.2 cm). To elucidate mulch characteristics that contributed to weed control, photosynthetic active radiation (PAR) was recorded underneath each mulch layer, moisture retention was monitored for 24 h following irrigation, and particle size was determined using standard soil sieves. HW reduced PAR (97%) more than did PB (90%) or PS (92%) at 1.3 cm, but few or no differences were noted between mulches at greater mulch depths. HW also contained the highest percentage of small particles and consequently retained more water (29%), than PB (14%) or PS (22%) 24 h following a simulated irrigation event. Emergence of large crabgrass and garden spurge was consistently greater when seeds were placed on top of the mulch, compared to seeds placed below. Emergence of both species also tended to respond to increasing depth in a quadratic manner, indicating that once a critical level of mulch was applied (2.5 to 5 cm), further reductions in weed emergence would not be observed, at least over the short term (12 wk). PB and PS tended to provide a greater reduction in emergence of both species compared to HW. This research also indicates that larger particle materials such as PB or PS would be advantageous because of their ability to suppress weed emergence regardless of seed position.
To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Background:
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
Methods:
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
Results:
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Conclusions:
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
Core facilities play crucial roles in carrying out the academic research mission by making available to researchers advanced technologies, facilities, or expertise that are unfeasible for most investigators to obtain on their own. To facilitate translational science through support of core services, the University of California, Los Angeles Clinical and Translational Science Institute (UCLA CTSI) created a Core Voucher program. The underlying premise is that by actively promoting interplay between researchers and core facilities, a dynamic feedback loop could be established that could enhance both groups, the productivity of the former and the relevance of the latter. Our primary goal was to give translational investigators what they need to pursue their immediate projects at hand.
Methods:
To implement this system across four noncontiguous campuses, open-source web-accessible software applications were created that were scalable and could efficiently administer investigator submissions and subsequent reviews in a multicampus fashion.
Results:
In the past five years, we have processed over 1400 applications submitted by over 750 individual faculty members across both clinical and nonclinical departments. In total, 1926 core requests were made in conjunction with 1467 submitted proposals. The top 10 most popular cores accounted for 50% of all requests, and the top half of the most popular cores accounted for 90% of all requests.
Conclusion:
Tracking investigator demand provides a unique window into what are the high- and low-priority core services that best support translational research.
OBJECTIVES/SPECIFIC AIMS: The objective of this study was to prospectively assess caregiver-perceived barriers to accessing post-acute care for their injured child and determine if caregivers report ongoing, unmet health needs for their children after trauma. METHODS/STUDY POPULATION: This was a prospective cohort study that followed 50 participants for 6 months and administered surveys to parents of children who are admitted to a pediatric level 1 trauma center for injury. Surveys were given bi-weekly regarding care children received after hospital discharge. At 3 months, parents were surveyed over the phone on whether they were able to access all needed health services and if there were any perceived barriers to obtaining or providing at-home care. At 6 months, parents were given the Child & Family Follow-up Survey to assess ongoing physical, mental, social, and scholastic needs. Free responses and transcribed interviews were analyzed using thematic content analysis and frequencies are reported for discrete data. RESULTS/ANTICIPATED RESULTS: Out of 50 families recruited, 47 completed follow-up assessments. At 3 months, common themes regarding challenges after hospital discharge included difficulty scheduling specialist care; uncertainty in managing their child’s pain; transitioning home without enough knowledge to meet their child’s medical needs; lack of communication between multiple providers; distress at having providers release children to full activities before caregivers were comfortable. At 6 months, approximately 24% of parents reported children had ongoing cognitive limitations, 29% reported emotional problems, 19% reported physical limitations, 33.3% reported difficulty in school, and 15% reported play/social difficulties. DISCUSSION/SIGNIFICANCE OF IMPACT: Evidence suggests families face significant barriers in accessing follow-up care, despite nearly universal health insurance coverage for children. Further, a large percentage of parents report ongoing health needs, despite the majority of the cohort having only mild or moderate severity injuries. Making follow-up care more patient-centered for families of traumatically injured children may improve compliance with medical regiments and reduce the likelihood of future disability. Examples of this may be coordinating care among multiple specialty providers, so that patients with multiple injuries can schedule multiple follow-up appointments on the same day. Additionally, more caregiver education on administering pain medication, caring for wounds, and safe practices for returning to full activities would be beneficial for families.
OBJECTIVES/SPECIFIC AIMS: The objective of this study is to determine predictors and motives for sustained opioid use, prescription misuse, and nonmedical opioid use in the adolescent trauma population. METHODS/STUDY POPULATION: This is a prospective cohort study that will follow patients for 1 year and administer surveys to patients on prescription opioid usage; substance use; utilization of pain management and mental health services; mental and physical health conditions; and behavioral and social risk factors. Patient eligibility criteria include: (1) patient is 12–18 years of age; (2) admitted for trauma; (3) english speaking; (4) resides within Indianapolis, IN metropolitan area; and (5) consent can be obtained from a parent or guardian. Patients with severe brain injuries or other injuries that prevent survey participation will be excluded. The patient sample will comprise of 50 traumatically injured adolescents admitted for trauma who will be followed for 12 months after discharge. RESULTS/ANTICIPATED RESULTS: We expect that the results of this study will identify multiple risk factors for sustained opioid use that can be used to create targeted interventions to reduce opioid misuse in the adolescent trauma population. Clinical predictors such as opioid type, dosage, and duration that can be modified to reduce the risk of long-term opioid use will be identified. We expect to elucidate clinical, behavioral, and social risk factors that increase the likelihood adolescents will misuse their medication and initiate nonmedical opioid use. DISCUSSION/SIGNIFICANCE OF IMPACT: Trauma is a surgical specialty that often has limited collaboration with behavioral health providers. Collaborative care models for trauma patients to adequately address the psychological impact of a traumatic injury have become more common in recent years. These models have primarily been concerned with the prevention of post-traumatic stress disorder. We would like to apply the findings of our research to better understand what motivates adolescents to misuse pain medications as well as how clinical, individual, behavioral, and social factors affect medication usage. This may help identify patients at greater risk of developing a SUD by asking questions not commonly addressed in the hospital setting. For example, similar to how trauma centers have mandated brief interventions on alcohol use be performed for center verification, screening patients’ on their social environment may identify patients at greater risk for SUD than assumed. The long-term goal would be to prevent opioid use disorders in injured adolescents by providing better post-acute care support, possibly by developing and implementing a collaborative care model that addresses opioid use. Additionally, we believe our findings could be applied in the acute care setting as well to help inform opioid prescribing and pain management methods in the acute phase of an injury. Genetic testing to determine which opioid to prescribe pediatric surgical patients is starting to be done at some pediatric hospitals. Certain genes determine which specific opioid is most effective in controlling a patient’s pain and, further, using the optimal opioid medication can also reduce overdose. Our findings may help refine prescribing patterns that could increase or decrease the likelihood of developing SUD in patients with certain genetic, clinical, behavioral, and social characteristics.