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The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
There is increasing emphasis on reducing the use and improving the safety of mechanical restraint (MR) in psychiatric settings, and on improving the quality of evidence for outcomes. To date, however, a systematic appraisal of evidence has been lacking.
Methods
We included studies of adults (aged 18–65) admitted to inpatient psychiatric settings. We included primary randomised or observational studies from 1990 onwards that reported patterns of MR and/or outcomes associated with MR, and qualitative studies referring to an index admission or MR episode. We presented prevalence data only for studies from 2010 onwards. The risk of bias was assessed using an adapted checklist for randomised/observational studies and the Newcastle-Ottawa scale for interventional studies.
Results
We included 83 articles on 73 studies from 1990–2022, from 22 countries. Twenty-six studies, from 11 countries, 2010 onwards, presented data from on proportions of patients/admissions affected by MR. There was wide variation in prevalence (<1–51%). This appeared to be mostly due to variations in standard protocols between countries and regions, which dictated use compared to other restrictive practices such as seclusion. Indications for MR were typically broad (violence/aggression, danger to self or property). The most consistently associated factors were the early phase of admission, male sex, and younger age. Ward and staff factors were inconsistently examined. There was limited reporting of patient experience or positive effects.
Conclusions
MR remains widely practiced in psychiatric settings internationally, with considerable variation in rates, but few high-quality studies of outcomes. There was a notable lack of studies investigating different types of restraint, indications, clinical factors associated with use, the impact of ethnicity and language, and evidence for outcomes. Studies examining these factors are crucial areas for future research. In limiting the use of MR, some ward-level interventions show promise, however, wider contextual factors are often overlooked.
In schizophrenia (SZ), impairments in cognitive functions, such as working memory, have been associated with alterations in certain types of inhibitory neurons that utilize the neurotransmitter γ-aminobutyric acid (GABA) in the dorsolateral prefrontal cortex (DLPFC). For example, GABA neurons that express parvalbumin (PV) or somatostatin (SST) have more prominent gene expression alterations than those that express vasoactive intestinal peptide (VIP). In bipolar disorder (BD) and major depression (MD), which exhibit similar, but less severe, cognitive impairments than SZ, alterations of transcript levels in GABA neurons have also been reported. However, the extent to which GABA neuron subtype-selective transcripts in the DLPFC are affected, and the relative magnitudes of the diagnosis-associated effects, have not been directly compared across SZ, BD, and MD in the same study.
Methods
We used quantitative polymerase chain reaction to examine levels of GABA neuron subtype-selective transcripts (PV, potassium voltage-gated channel modifier subfamily-S member-3, SST, VIP, and calretinin mRNAs), as well as the pan-GABA neuron marker 67 kDa glutamate decarboxylase mRNA, in DLPFC total gray matter of 160 individuals, including those with SZ, BD, or MD and unaffected comparison (UC) individuals.
Results
Relative to UC individuals, individuals with SZ exhibited large deficits in levels of all transcripts except for calretinin mRNA, whereas individuals with BD or MD showed a marked deficit only for PV or SST mRNAs, respectively.
Conclusions
These findings suggest that broader and more severe alterations in DLPFC GABA neurons might contribute to the greater cognitive impairments in SZ relative to BD and MD.
This study identified 26 late invasive primary surgical site infection (IP-SSI) within 4–12 months of transplantation among 2073 SOT recipients at Duke University Hospital over the period 2015–2019. Thoracic organ transplants accounted for 25 late IP-SSI. Surveillance for late IP-SSI should be maintained for at least one year following transplant.
Children with neurodevelopmental disorders (NDDs) commonly experience attentional and executive function (EF) difficulties that are negatively associated with academic success, psychosocial functioning, and quality of life. Access to early and consistent interventions is a critical protective factor and there are recommendations to deliver cognitive interventions in schools; however, current cognitive interventions are expensive and/or inaccessible, particularly for those with limited resources and/or in remote communities. The current study evaluated the school-based implementation of two game-based interventions in children with NDDs: 1) a novel neurocognitive attention/EF intervention (Dino Island; DI), and 2) a commercial educational intervention (Adventure Academy; AA). DI is a game-based attention/EF intervention specifically developed for children for delivery in community-based settings.
Participants and Methods:
Thirty five children with NDDs (ages 5-13 years) and 17 EAs participated. EAs completed on-line training to deliver the interventions to assigned students at their respective schools (3x/week, 40-60 minutes/session, 8 weeks, 14 hours in total). We gathered baseline child and EA demographic data, completed pre-intervention EA interviews, and conducted regular fidelity checks throughout the interventions. Implementation data included paper-pencil tracking forms, computerized game analytic data, and online communications.
Results:
Using a mixed methods approach we evaluated the following implementation outcomes: fidelity, feasibility, acceptability, and barriers. Overall, no meaningful between-group differences were found in EA or child demographics, except for total number of years worked as an EA (M = 17.18 for AA and 9.15 for DI; t (22) = - 4.34, p < .01) and EA gender (χ2 (1) = 6.11, p < .05). For both groups, EA age was significantly associated with the number of sessions played [DI (r = .847, p < .01), AA (r = .986, p < .05)]. EAs who knew their student better completed longer sessions [DI (r = .646), AA (r = .973)], all ps < .05]. The number of years worked as an EA was negatively associated with the total intervention hours for both groups. Qualitative interview data indicated that most EAs found DI valuable and feasible to deliver in their classrooms, whereas more implementation challenges were identified with AA. Barriers common to both groups included technical difficulties (e.g., game access, internet firewalls), environmental barriers (e.g., distractions in surroundings, time of the year), child factors (e.g., lack of motivation, attentional difficulties, frustration), and game-specific factors (e.g., difficulty level progression). Barriers specific to DI included greater challenges in motivating children as a function of difficulty level progression. Furthermore, given the comprehensive nature of training required for delivery, EAs needed a longer time to complete the training for DI. Nevertheless, many EAs in the DI group found the training helpful, with a potential to generalize to other children in the classroom.
Conclusions:
The availability of affordable, accessible, and effective cognitive intervention is important for children with NDDs. We found that delivery of a novel cognitive intervention by EAs was feasible and acceptable, with similarities and differences in implementation facilitators/barriers between the cognitive and commercialized academic intervention. Recommendations regarding strategies for successful school-based implementation of neurocognitive intervention will be elaborated on in the poster.
Executive functions (EFs) are considered to be both unitary and diverse functions with common conceptualizations consisting of inhibitory control, working memory, and cognitive flexibility. Current research indicates that these abilities develop along different timelines and that working memory and inhibitory control may be foundational for cognitive flexibility, or the ability to shift attention between tasks or operations. Very few interventions target cognitive flexibility despite its importance for academic or occupational tasks, social skills, problem-solving, and goal-directed behavior in general, and the ability is commonly impaired in individuals with neurodevelopmental disorders (NDDs) such as autism spectrum disorder, attention deficit hyperactivity disorder, and learning disorders. The current study investigated a tablet-based cognitive flexibility intervention, Dino Island (DI), that combines a game-based, process-specific intervention with compensatory metacognitive strategies as delivered by classroom aides within a school setting.
Participants and Methods:
20 children between ages 6-12 years (x̄ = 10.83 years) with NDDs and identified executive function deficits and their assigned classroom aides (i.e., “interventionists”) were randomly assigned to either DI or an educational game control condition. Interventionists completed a 2-4 hour online training course and a brief, remote Q&A session with the research team, which provided key information for delivering the intervention such as game-play and metacognitive/behavioral strategy instruction. Fidelity checks were conducted weekly. Interventionists were instructed to deliver 14-16 hours of intervention during the school day over 6-8 weeks, divided into 3-4 weekly sessions of 30-60 minutes each. Baseline and post-intervention assessments consisted of cognitive measures of cognitive flexibility (Minnesota Executive Function Scale), working memory (Weschler Intelligence Scales for Children, 4th Edn. Integrated Spatial Span) and parent-completed EF rating scales (Behavior Rating Inventory of Executive Function).
Results:
Samples sizes were smaller than expected due to COVID-19 related disruptions within schools, so nonparametric analyses were conducted to explore trends in the data. Results of the Mann-Whitney U test indicated that participants within the DI condition made greater gains in cognitive flexibility with a trend towards significance (p = 0.115. After dummy coding for positive change, results also indicated that gains in spatial working memory differed by condition (p = 0.127). Similarly, gains in task monitoring trended towards significant difference by condition.
Conclusions:
DI, a novel EF intervention, may be beneficial to cognitive flexibility, working memory, and monitoring skills within youth with EF deficits. Though there were many absences and upheavals within the participating schools related to COVID-19, it is promising to see differences in outcomes with such a small sample. This poster will expand upon the current results as well as future directions for the DI intervention.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
Clinical trial processes are unnecessarily inefficient and costly, slowing the translation of medical discoveries into treatments for people living with disease. To reduce redundancies and inefficiencies, a group of clinical trial experts developed a framework for clinical trial site readiness based on existing trial site qualifications from sponsors. The site readiness practices are encompassed within six domains: research team, infrastructure, study management, data collection and management, quality oversight, and ethics and safety. Implementation of this framework for clinical trial sites would reduce inefficiencies in trial conduct and help prepare new sites to enter the clinical trials enterprise, with the potential to improve the reach of clinical trials to underserved communities. Moreover, the framework holds benefits for trial sponsors, contract research organizations, trade associations, trial participants, and the public. For novice sites considering future trials, we provide a framework for site preparation and the engagement of stakeholders. For experienced sites, the framework can be used to assess current practices and inform and engage sponsors, staff, and participants. Details in the supplementary materials provide easy access to key regulatory documents and resources. Invited perspective articles provide greater depth from a systems, DEIA (diversity, equity, inclusion, and accessibility) and decentralized trials perspective.
Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother–infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.
Clozapine dose assessment in treatment-refractory schizophrenia is complicated. There is a narrow margin between an effective and a potentially toxic dose and wide inter-individual variation in clozapine metabolic capacity. Moreover, factors such as changes in smoking habit, infection/inflammation, co-prescription of certain drugs, notably fluvoxamine, and age alter the dose requirement within individuals. Therapeutic drug monitoring (TDM) of plasma clozapine and N-desmethylclozapine (norclozapine) can help assess adherence, guide dosage and guard against toxicity. This article gives an overview of clozapine pharmacokinetics and factors affecting clozapine dose requirements. It then outlines the procedures and processes of clozapine TDM, from taking the blood sample for laboratory assay or point-of-contact (finger-prick) testing (POCT) to interpreting and acting on the results.
To evaluate variables that affect risk of contamination for endoscopic retrograde cholangiopancreatography and endoscopic ultrasound endoscopes.
Design:
Observational, quality improvement study.
Setting:
University medical center with a gastrointestinal endoscopy service performing ∼1,000 endoscopic retrograde cholangiopancreatography and ∼1,000 endoscopic ultrasound endoscope procedures annually.
Methods:
Duodenoscope and linear echoendoscope sampling (from the elevator mechanism and instrument channel) was performed from June 2020 through September 2021. Operational changes during this period included standard reprocessing with high-level disinfection with ethylene oxide gas sterilization (HLD–ETO) was switched to double high-level disinfection (dHLD) (June 16, 2020–July 15, 2020), and duodenoscopes changed to disposable tip model (March 2021). The frequency of contamination for the co-primary outcomes were characterized by calculated risk ratios.
Results:
The overall pathogenic contamination rate was 4.72% (6 of 127). Compared to duodenoscopes, linear echoendoscopes had a contamination risk ratio of 3.64 (95% confidence interval [CI], 0.69–19.1). Reprocessing using HLD-ETO was associated with a contamination risk ratio of 0.29 (95% CI, 0.06–1.54). Linear echoendoscopes undergoing dHLD had the highest risk of contamination (2 of 18, 11.1%), and duodenoscopes undergoing HLD-ETO and the lowest risk of contamination (0 of 53, 0%). Duodenoscopes with a disposable tip had a 0% contamination rate (0 of 27).
Conclusions:
We did not detect a significant reduction in endoscope contamination using HLD-ETO versus dHLD reprocessing. Linear echoendoscopes have a risk of contamination similar to that of duodenoscopes. Disposable tips may reduce the risk of duodenoscope contamination.
Despite an elevated risk of psychopathology stemming from COVID-19-related stress, many essential workers stigmatise and avoid psychiatric care. This randomised controlled trial was designed to compare five versions of a social-contact-based brief video intervention for essential workers, differing by protagonist gender and race/ethnicity.
Aims
We examined intervention efficacy on treatment-related stigma (‘stigma’) and openness to seeking treatment (‘openness’), especially among workers who had not received prior mental healthcare. We assessed effectiveness and whether viewer/protagonist demographic concordance heightened effectiveness.
Method
Essential workers (N = 2734) randomly viewed a control video or brief video of an actor portraying an essential worker describing hardships, COVID-related anxiety and depression, and psychotherapy benefits. Five video versions (Black/Latinx/White and male/female) followed an identical 3 min script. Half the intervention group participants rewatched their video 14 days later. Stigma and openness were assessed at baseline, post-intervention, and at 14- and 30-day follow-ups. Trial registration: NCT04964570.
Results
All video intervention groups reported immediately decreased stigma (P < 0.0001; Cohen's d = 0.10) and increased openness (P < 0.0001; d = 0.23). The initial increase in openness was largely maintained in the repeated-video group at day 14 (P < 0.0001; d = 0.18), particularly among viewers without history of psychiatric treatment (P < 0.0001; d = 0.32). Increases were not sustained at follow-up. Female participants viewing a female protagonist and Black participants viewing a Black protagonist demonstrated greater openness than other demographic pairings.
Conclusions
Brief video-based interventions improved immediate stigma and openness. Greater effects among female and Black individuals viewing demographically matched protagonists emphasise the value of tailored interventions, especially for socially oppressed groups. This easily disseminated intervention may proactively increase care-seeking, encouraging treatment among workers in need. Future studies should examine intervention mechanisms and whether linking referrals to psychiatric services generates treatment-seeking.
A terrestrial (lacustrine and fluvial) palaeoclimate record from Hoxne (Suffolk, UK) shows two temperate phases separated by a cold episode, correlated with MIS 11 subdivisions corresponding to isotopic events 11.3 (Hoxnian interglacial period), 11.24 (Stratum C cold interval), and 11.23 (warm interval with evidence of human presence). A robust, reproducible multiproxy consensus approach validates and combines quantitative palaeotemperature reconstructions from three invertebrate groups (beetles, chironomids, and ostracods) and plant indicator taxa with qualitative implications of molluscs and small vertebrates. Compared with the present, interglacial mean monthly air temperatures were similar or up to 4.0°C higher in summer, but similar or as much as 3.0°C lower in winter; the Stratum C cold interval, following prolonged nondeposition or erosion of the lake bed, experienced summers 2.5°C cooler and winters between 5°C and 10°C cooler than at present. Possible reworking of fossils into Stratum C from underlying interglacial assemblages is taken into account. Oxygen and carbon isotopes from ostracod shells indicate evaporatively enriched lake water during Stratum C deposition. Comparative evaluation shows that proxy-based palaeoclimate reconstruction methods are best tested against each other and, if validated, can be used to generate more refined and robust results through multiproxy consensus.
Wetland sediments are valuable archives of environmental change but can be challenging to date. Terrestrial macrofossils are often sparse, resulting in radiocarbon (14C) dating of less desirable organic fractions. An alternative approach for capturing changes in atmospheric 14C is the use of terrestrial microfossils. We 14C date pollen microfossils from two Australian wetland sediment sequences and compare these to ages from other sediment fractions (n = 56). For the Holocene Lake Werri Berri record, pollen 14C ages are consistent with 14C ages on bulk sediment and humic acids (n = 14), whilst Stable Polycyclic Aromatic Carbon (SPAC) 14C ages (n = 4) are significantly younger. For Welsby Lagoon, pollen concentrate 14C ages (n = 21) provide a stratigraphically coherent sequence back to 50 ka BP. 14C ages from humic acid and >100 µm fractions (n = 13) are inconsistent, and often substantially younger than pollen ages. Our comparison of Bayesian age-depth models, developed in Oxcal, Bacon and Undatable, highlight the strengths and weaknesses of the different programs for straightforward and more complex chrono-stratigraphic records. All models display broad similarities but differences in modeled age-uncertainty, particularly when age constraints are sparse. Intensive dating of wetland sequences improves the identification of outliers and generation of robust age models, regardless of program used.