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Retrospective self-report is typically used for diagnosing previous pediatric traumatic brain injury (TBI). A new semi-structured interview instrument (New Mexico Assessment of Pediatric TBI; NewMAP TBI) investigated test–retest reliability for TBI characteristics in both the TBI that qualified for study inclusion and for lifetime history of TBI.
One-hundred and eight-four mTBI (aged 8–18), 156 matched healthy controls (HC), and their parents completed the NewMAP TBI within 11 days (subacute; SA) and 4 months (early chronic; EC) of injury, with a subset returning at 1 year (late chronic; LC).
The test–retest reliability of common TBI characteristics [loss of consciousness (LOC), post-traumatic amnesia (PTA), retrograde amnesia, confusion/disorientation] and post-concussion symptoms (PCS) were examined across study visits. Aside from PTA, binary reporting (present/absent) for all TBI characteristics exhibited acceptable (≥0.60) test–retest reliability for both Qualifying and Remote TBIs across all three visits. In contrast, reliability for continuous data (exact duration) was generally unacceptable, with LOC and PCS meeting acceptable criteria at only half of the assessments. Transforming continuous self-report ratings into discrete categories based on injury severity resulted in acceptable reliability. Reliability was not strongly affected by the parent completing the NewMAP TBI.
Categorical reporting of TBI characteristics in children and adolescents can aid clinicians in retrospectively obtaining reliable estimates of TBI severity up to a year post-injury. However, test–retest reliability is strongly impacted by the initial data distribution, selected statistical methods, and potentially by patient difficulty in distinguishing among conceptually similar medical concepts (i.e., PTA vs. confusion).
The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD.
Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support.
Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein.
Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.
Atom probe tomography, and related methods, probe the composition and the three-dimensional architecture of materials. The software tools which microscopists use, and how these tools are connected into workflows, make a substantial contribution to the accuracy and precision of such material characterization experiments. Typically, we adapt methods from other communities like mathematics, data science, computational geometry, artificial intelligence, or scientific computing. We also realize that improving on research data management is a challenge when it comes to align with the FAIR data stewardship principles. Faced with this global challenge, we are convinced it is useful to join forces. Here, we report the results and challenges with an inter-laboratory call for developing test cases for several types of atom probe microscopy software tools. The results support why defining detailed recipes of software workflows and sharing these recipes is necessary and rewarding: Open source tools and (meta)data exchange can help to make our day-to-day data processing tasks become more efficient, the training of new users and knowledge transfer become easier, and assist us with automated quantification of uncertainties to gain access to substantiated results.
Researchers, clinicians and patients are increasingly using real-time monitoring methods to understand and predict suicidal thoughts and behaviours. These methods involve frequently assessing suicidal thoughts, but it is not known whether asking about suicide repeatedly is iatrogenic. We tested two questions about this approach: (a) does repeatedly assessing suicidal thinking over short periods of time increase suicidal thinking, and (b) is more frequent assessment of suicidal thinking associated with more severe suicidal thinking? In a real-time monitoring study (n = 101 participants, n = 12 793 surveys), we found no evidence to support the notion that repeated assessment of suicidal thoughts is iatrogenic.
Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes.
Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay.
One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004).
Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.
The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates’ mental health and patient outcomes.
Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15–20 min modules, totaling 1.5–2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments.
Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = −0.41), peritraumatic distress (d = −0.24), and experiential avoidance (d = −0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = −0.94), depression (d = −0.23), anxiety (d = −0.29), and experiential avoidance (d = −0.30).
Significance of results
Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.
Introduced mammalian predators are responsible for the decline and extinction of many native species, with rats (genus Rattus) being among the most widespread and damaging invaders worldwide. In a naturally fragmented landscape, we demonstrate the multi-year effectiveness of snap traps in the removal of Rattus rattus and Rattus exulans from lava-surrounded forest fragments ranging in size from <0.1 to >10 ha. Relative to other studies, we observed low levels of fragment recolonization. Larger rats were the first to be trapped, with the average size of trapped rats decreasing over time. Rat removal led to distinct shifts in the foraging height and location of mongooses and mice, emphasizing the need to focus control efforts on multiple invasive species at once. Furthermore, because of a specially designed trap casing, we observed low non-target capture rates, suggesting that on Hawai‘i and similar islands lacking native rodents the risk of killing non-target species in snap traps may be lower than the application of rodenticides, which have the potential to contaminate food webs. These efforts demonstrate that targeted snap-trapping is an effective removal method for invasive rats in fragmented habitats and that, where used, monitoring of recolonization should be included as part of a comprehensive biodiversity management strategy.
This volume contains nine survey articles based on plenary lectures given at the 28th British Combinatorial Conference, hosted online by Durham University in July 2021. This biennial conference is a well-established international event, attracting speakers from around the world. Written by some of the foremost researchers in the field, these surveys provide up-to-date overviews of several areas of contemporary interest in combinatorics. Topics discussed include maximal subgroups of finite simple groups, Hasse–Weil type theorems and relevant classes of polynomial functions, the partition complex, the graph isomorphism problem, and Borel combinatorics. Representing a snapshot of current developments in combinatorics, this book will be of interest to researchers and graduate students in mathematics and theoretical computer science.
The limitations of self-report measures of dietary intake are well-known. Novel, technology-based measures of dietary intake may provide a more accurate, less burdensome alternative to existing tools. The first objective of this study was to compare participant burden for two technology-based measures of dietary intake among school-age children: the Automated-Self-Administered 24-hour Dietary Assessment Tool-2018 (ASA24-2018) and the Remote Food Photography Method (RFPM). The second objective was to compare reported energy intake for each method to the Estimated Energy Requirement for each child, as a benchmark for actual intake. Forty parent–child dyads participated in two, 3-d dietary assessments: a parent proxy-reported version of the ASA24 and the RFPM. A parent survey was subsequently administered to compare satisfaction, ease of use and burden with each method. A linear mixed model examined differences in total daily energy intake between assessments, and between each assessment method and the Estimated Energy Requirement (EER). Reported energy intake was 379 kcal higher with the ASA24 than the RFPM (P = 0·0002). Reported energy intake with the ASA24 was 231 kcal higher than the EER (P = 0·008). Reported energy intake with the RFPM did not differ significantly from the EER (difference in predicted means = −148 kcal, P = 0·09). Median satisfaction and ease of use scores were five out of six for both methods. A higher proportion of parents reported that the ASA24 was more time-consuming than the RFPM (74·4 % v. 25·6 %, P = 0·002). Utilisation of both methods is warranted given their high satisfaction among parents.
On September 20, 2017, Hurricane Maria, a Category 4 hurricane, swept across Puerto Rico (PR), wreaking devastation to PR’s power, water, and health care infrastructure. To address the imminent humanitarian crisis, the US government mobilized Federal Medical Shelters (FMS) to serve the needs of hurricane victims. This study’s objective was to provide a description of the patients seeking emergency care at FMS and the changes in their needs over time.
This retrospective, cross-sectional study included all patients presenting to the FMS Manatí from October 6, two weeks after Hurricane Maria’s landfall, to November 2, 2017. Categories were created to catalogue the nature of new acute medical issues by patients presenting to the Shelter. Descriptive, graphical analyses were performed to assess changes to presenting complaints over time, and by age groups defined as infant (age ≤1 years), child (1 year < age ≤10 years), adolescent (10 years < age ≤ 25 years), and adult (age > 25 years).
Over the 30-day period, 5,268 patients were seen in the FMS seeking medical care (average 188.1 patients per day), spending less than five hours in the facility. The distribution of patients’ age was bimodal: the first peak at one year and the second at age 50. The most common patient complaint was infection (38.8%), then musculoskeletal (MSK) complaints (11.8%) and management of chronic medical conditions (11.8%). The proportion of patients presenting with chronic disease complaints declined over the course of the period of observation (21.4% on Day 4 to 8.0% on Day 30) while the proportion of patients presenting with infection increased (31.0% on Day 4 to 48.6% on Day 30). Infection complaints were highest in all age groups, but most in infxants (80.2%), while MSK and chronic disease complaints were highest in adults (14.9% and 14.9%, respectively).
Infection treatment and chronic disease management were important medical needs facing patients seeking care at FMS Manatí after Hurricane Maria. These findings suggest that basic needs related to sanitation and shelter remained important weeks after the hurricane, and a focus on access to medications, infection control, and injury prevention/management after a disaster needs to be prioritized during disaster response.
Delineating the proximal urethra can be critical for radiotherapy planning but is challenging on computerised tomography (CT) imaging.
Materials and methods:
We trialed a novel non-invasive technique to allow visualisation of the proximal urethra using a rapid sequence magnetic resonance imaging (MRI) protocol to visualise the urinary flow in patients voiding during the simulation scan.
Of the seven patients enrolled, four were able to void during the MRI scan. For these four patients, direct visualisation of urinary flow through the proximal urethra was achieved. The average volume of the proximal urethra contoured on voiding MRI was significantly higher than the proximal urethra contoured on CT, 4·07 and 1·60 cc, respectively (p = 0·02). The proximal urethra location also differed; the Dice coefficient average was 0·28 (range 0–0·62).
In this small, proof-of-concept prospective clinical trial, the volume and location of the proximal urethra differed significantly when contoured on a voiding MRI scan compared to that determined by a conventional CT simulation. The shape of the proximal urethra on voiding MRI may be more anatomically correct compared to the proximal urethra shape determined with a semi-rigid catheter in place.
Pre-analysis plans (PAPs) have been championed as a solution to the problem of research credibility, but without any evidence that PAPs actually bolster the credibility of research. We analyze a representative sample of 195 PAPs registered on the Evidence in Governance and Politics (EGAP) and American Economic Association (AEA) registration platforms to assess whether PAPs registered in the early days of pre-registration (2011–2016) were sufficiently clear, precise, and comprehensive to achieve their objective of preventing “fishing” and reducing the scope for post-hoc adjustment of research hypotheses. We also analyze a subset of ninety-three PAPs from projects that resulted in publicly available papers to ascertain how faithfully they adhere to their pre-registered specifications and hypotheses. We find significant variation in the extent to which PAPs registered during this period accomplished the goals they were designed to achieve. We discuss these findings in light of both the costs and benefits of pre-registration, showing how our results speak to the various arguments that have been made in support of and against PAPs. We also highlight the norms and institutions that will need to be strengthened to augment the power of PAPs to improve research credibility and to create incentives for researchers to invest in both producing and policing them.
Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset.
Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups.
Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups.
PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages.
Fundamental knowledge about the processes that control the functioning of the biophysical workings of ecosystems has expanded exponentially since the late 1960s. Scientists, then, had only primitive knowledge about C, N, P, S, and H2O cycles; plant, animal, and soil microbial interactions and dynamics; and land, atmosphere, and water interactions. With the advent of systems ecology paradigm (SEP) and the explosion of technologies supporting field and laboratory research, scientists throughout the world were able to assemble the knowledge base known today as ecosystem science. This chapter describes, through the eyes of scientists associated with the Natural Resource Ecology Laboratory (NREL) at Colorado State University (CSU), the evolution of the SEP in discovering how biophysical systems at small scales (ecological sites, landscapes) function as systems. The NREL and CSU are epicenters of the development of ecosystem science. Later, that knowledge, including humans as components of ecosystems, has been applied to small regions, regions, and the globe. Many research results that have formed the foundation for ecosystem science and management of natural resources, terrestrial environments, and its waters are described in this chapter. Throughout are direct and implicit references to the vital collaborations with the global network of ecosystem scientists.
ABSTRACT IMPACT: Optimization of primary septal-hippocampal co-cultures facilitates studying central cholinergic synapse formation and dysfunction OBJECTIVES/GOALS: Septal cholinergic innervation to the hippocampus is critical for normal learning and memory and is severely degenerated in Alzheimer’s disease. To understand the molecular events underlying this loss, we optimized a primary septal-hippocampal co-culture system that facilitates the study of central cholinergic synapses. METHODS/STUDY POPULATION: We developed an optimized in vitro septal-hippocampal co-culture system modified from previously published protocols. Briefly, hippocampal and septal tissue were harvested from embryonic day 19 (E19) Sprague-Dawley rats, digested with 0.1% trypsin, and an equal number of cells from each region plated onto coverslips coated with poly-D-lysine and laminin at a final density of 300 cells/mm2. We use immunostaining with validated primary antibodies and a fluorescent binding assay, together with confocal microscopy, to determine the structure of cholinergic synapses that are 1) native, 2) mammalian, 3) CNS derived, 4) comprised of physiological synaptic partners, and 5) developmentally mature. RESULTS/ANTICIPATED RESULTS: After DIV21, co-cultures maintained a healthy morphology. A subpopulation of neurons strongly expressed the cholinergic markers vesicular ACh transporter (vAChT), choline acetyltransferase (ChAT), and the high-affinity choline transporter (ChT1), whereas most neurons lacked vAChT expression and were presumably glutamatergic or GABAergic. The percentage of cholinergic neurons attained in the co-culture is ˜5-7%. The size of these cholinergic neurons is strikingly similar to that reported for BFCNs in the intact brain (mean 30μm, range 18-43μm). All sampled cholinergic neurons (28/28 neurons) also expressed molecular machinery necessary for GABA release. Staining for a cholinergic postsynaptic marker shows that 63% of the contacts made with are synaptic. DISCUSSION/SIGNIFICANCE OF FINDINGS: Primary septal-hippocampal co-cultured neurons have not been exploited extensively in the field, perhaps due to the difficulty in maintaining such cultures for extended periods. Here, we optimized an in vitro septal-hippocampal co-culture system, a powerful tool to comprehensively analyze central cholinergic synapse formation and dysfunction.