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In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
We synthesize sea-level science developments, priorities and practitioner needs at the end of the 10-year World Climate Research Program Grand Challenge ’Regional Sea-Level Change and Coastal Impacts’. Sea-level science and associated climate services have progressed but are unevenly distributed. There remains deep uncertainty concerning high-end and long-term sea-level projections due to indeterminate emissions, the ice sheet response and other climate tipping points. These are priorities for sea-level science. At the same time practitioners need climate services that provide localized information including median and curated high-end sea-level projections for long-term planning, together with information to address near-term pressures, including extreme sea level-related hazards and land subsidence, which can greatly exceed current rates of climate-induced sea-level rise in some populous coastal settlements. To maximise the impact of scientific knowledge, ongoing co-production between science and practitioner communities is essential. Here we report on recent progress and ways forward for the next decade.
Rift propagation, rather than basal melt, drives the destabilization and disintegration of the Thwaites Eastern Ice Shelf. Since 2016, rifts have episodically advanced throughout the central ice-shelf area, with rapid propagation events occurring during austral spring. The ice shelf's speed has increased by ~70% during this period, transitioning from a rate of 1.65 m d−1 in 2019 to 2.85 m d−1 by early 2023 in the central area. The increase in longitudinal strain rates near the grounding zone has led to full-thickness rifts and melange-filled gaps since 2020. A recent sea-ice break out has accelerated retreat at the western calving front, effectively separating the ice shelf from what remained of its northwestern pinning point. Meanwhile, a distributed set of phase-sensitive radar measurements indicates that the basal melting rate is generally small, likely due to a widespread robust ocean stratification beneath the ice–ocean interface that suppresses basal melt despite the presence of substantial oceanic heat at depth. These observations in combination with damage modeling show that, while ocean forcing is responsible for triggering the current West Antarctic ice retreat, the Thwaites Eastern Ice Shelf is experiencing dynamic feedbacks over decadal timescales that are driving ice-shelf disintegration, now independent of basal melt.
Nasogastric tube (NGT) feeding against a patient's consent is an intervention that clinicians working in specialist mental health in-patient units may need to implement from time to time. Little research has explored clinician, patient and carer perspectives on good practice.
Aims
To use qualitative data from people with lived experience (PWLE), parents/carers and clinicians, to identify components of best practice when this intervention is required.
Method
PWLE and parents/carers were recruited via BEAT UK's eating disorder charity. Clinicians were recruited via a post on The British Eating Disorders Society's research page. Semi-structured interviews were administered, transcribed and thematically analysed.
Results
Thirty-six interviews took place and overlapping themes were identified. Participants spoke in relation to three themes: first, the significance of individualised care; second, the importance of communication; third, the impact of staff relationships. Sub-themes were identified and explored.
Conclusions
Good care evolved around positive staff relationships and individualised care planning rather than standard processes. The centrality of trust as an important mediator of outcome was identified, and this should be acknowledged in any service that delivers this intervention.
A new nematode genus and species, Paraspiralatus sakeri , is described from the stomach of a wild-caught, female saker falcon in Saudi Arabia. This spirurid differs from the nearest genus and species Spiralatus baeri Chabaud, Brygoo & Durette, 1963 in the shape of the pseudolabia, shape of the buccal capsule and absence of a large cephalic vesicle. In addition, third stage spirurid larvae were recovered for the first time from subcutaneous tissues of two houbara bustards. These had died in the Rahim Yar Khan Rehabilitation Center (Houbara Foundation International, Lahore, Pakistan) in Pakistan and were examined at the National Avian Research Center in the United Arab Emirates. The morphology of the larvae and host pathology are described. Comparative studies with the adult spirurids from the saker falcon showed each to have similar cephalic and pharyngeal morphological features to the adults described indicating they are probably the same species. Spirurid nematodes of the suborder Spirurina normally have an arthropod intermediate host. In view of the host, the site from which the larvae were recovered and the fact that this is a rare occurrence, the houbara bustard is considered to be a paratenic host.
Large-scale geological structures have controlled the long-term development of the bed and thus the flow of the West Antarctic Ice Sheet (WAIS). However, complete ice cover has obscured the age and exact positions of faults and geological boundaries beneath Thwaites Glacier and Pine Island Glacier, two major WAIS outlets in the Amundsen Sea sector. Here, we characterize the only rock outcrop between these two glaciers, which was exposed by the retreat of slow-flowing coastal ice in the early 2010s to form the new Sif Island. The island comprises granite, zircon U-Pb dated to ~177–174 Ma and characterized by initial ɛNd, 87Sr/86Sr and ɛHf isotope compositions of -2.3, 0.7061 and -1.3, respectively. These characteristics resemble Thurston Island/Antarctic Peninsula crustal block rocks, strongly suggesting that the Sif Island granite belongs to this province and placing the crustal block's boundary with the Marie Byrd Land province under Thwaites Glacier or its eastern shear margin. Low-temperature thermochronological data reveal that the granite underwent rapid cooling following emplacement, rapidly cooled again at ~100–90 Ma and then remained close to the Earth's surface until present. These data help date vertical displacement across the major tectonic structure beneath Pine Island Glacier to the Late Cretaceous.
Bayesian statistical approaches are extensively used in new statistical methods but have not been adopted at the same rate in clinical and translational (C&T) research. The goal of this paper is to accelerate the transition of new methods into practice by improving the C&T researcher’s ability to gain confidence in interpreting and implementing Bayesian analyses.
Methods:
We developed a Bayesian data analysis plan and implemented that plan for a two-arm clinical trial comparing the effectiveness of a new opioid in reducing time to discharge from the post-operative anesthesia unit and nerve block usage in surgery. Through this application, we offer a brief tutorial on Bayesian methods and exhibit how to apply four Bayesian statistical packages from STATA, SAS, and RStan to conduct linear and logistic regression analyses in clinical research.
Results:
The analysis results in our application were robust to statistical package and consistent across a wide range of prior distributions. STATA was the most approachable package for linear regression but was more limited in the models that could be fitted and easily summarized. SAS and R offered more straightforward documentation and data management for the posteriors. They also offered direct programming of the likelihood making them more easily extendable to complex problems.
Conclusion:
Bayesian analysis is now accessible to a broad range of data analysts and should be considered in more C&T research analyses. This will allow C&T research teams the ability to adopt and interpret Bayesian methodology in more complex problems where Bayesian approaches are often needed.
Early detection of ST-segment elevation myocardial infarction (STEMI) on the prehospital electrocardiogram (ECG) improves patient outcomes. Current software algorithms optimize sensitivity but have a high false-positive rate. The authors propose an algorithm to improve the specificity of STEMI diagnosis in the prehospital setting.
Methods:
A dataset of prehospital ECGs with verified outcomes was used to validate an algorithm to identify true and false-positive software interpretations of STEMI. Four criteria implicated in prior research to differentiate STEMI true positives were applied: heart rate <130, QRS <100, verification of ST-segment elevation, and absence of artifact. The test characteristics were calculated and regression analysis was used to examine the association between the number of criteria included and test characteristics.
Results:
There were 44,611 cases available. Of these, 1,193 were identified as STEMI by the software interpretation. Applying all four criteria had the highest positive likelihood ratio of 353 (95% CI, 201-595) and specificity of 99.96% (95% CI, 99.93-99.98), but the lowest sensitivity (14%; 95% CI, 11-17) and worst negative likelihood ratio (0.86; 95% CI, 0.84-0.89). There was a strong correlation between increased positive likelihood ratio (r2 = 0.90) and specificity (r2 = 0.85) with increasing number of criteria.
Conclusions:
Prehospital ECGs with a high probability of true STEMI can be accurately identified using these four criteria: heart rate <130, QRS <100, verification of ST-segment elevation, and absence of artifact. Applying these criteria to prehospital ECGs with software interpretations of STEMI could decrease false-positive field activations, while also reducing the need to rely on transmission for physician over-read. This can have significant clinical and quality implications for Emergency Medical Services (EMS) systems.
The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.
Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.
The concept of adminigration provides a much-needed lens in theorizing immigration enforcement, citizenship, and urban geographies. We define adminigration as the governance of immigrant community members through city-level policies and programs, whether or not these explicitly focus on immigrants. Our focus on adminigration involves three theoretical interventions: (1) bridging literature on immigrant bureaucratic incorporation and crimmigration to situate city-level administrative practices within immigration policymaking; (2) a focus on how localized definitions of membership, as enacted by cities, produce citizenship, legality, and illegality, and (3) the argument that these practices play out in space, resulting in variegated urban landscapes that are better characterized as a network than a level. We develop these points through a review of the literature on bureaucratic incorporation, crimmigration, citizenship, and the spatialization of immigration policymaking. To illustrate the utility of this framework, we conclude with a case study of adminigration in a California city that we call “Mayville.”
Nasogastric tube feeding under physical restraint is an intervention that clinicians working in specialist mental health in-patient units may need to implement.
Aims
To examine the impact of this intervention on people with lived experience, carers and staff.
Method
People with lived experience and parents and/or carers were recruited via UK eating disorder charity Beat. Clinicians were recruited via the British Eating Disorders Society's research forum. Qualitative semi-structured interviews were conducted and transcribed, and the results were thematically analysed.
Results
Thirty-six participants took part, and overlapping themes were identified. All participants spoke in relation to four themes: (a) the short-term impact on the patient; (b) the impact on those around the patient; (c) the long-term impact; and (d) the positive impact. Subthemes were identified and explored.
Conclusion
This lifesaving intervention can also negatively affect patients, parents and carers, peers and staff. Further research is needed to understand how interactions and environmental modifications can mitigate the negative impacts.
To identify the clinical characteristics of patients receiving nasogastric tube (NGT) feeding under physical restraint. Clinicians participated via professional networks and subsequent telephone contact. In addition to completing a survey, participants were invited to submit up to ten case studies.
Results
The survey response rate from in-patient units was 100% and 143 case studies were submitted. An estimated 622 patients received NGT feeding under restraint in England in 2020–2021. The most common diagnosis was anorexia nervosa (68.5–75.7%), with depression, anxiety and autism spectrum disorder the most frequent comorbidities. Patients receiving the intervention ranged from 11 to 60 years in age (mean 19.02 years). There was wide variation in duration of use, from once to daily for 312 weeks (mode 1 week; mean 29.1 weeks, s.d. = 50.8 weeks).
Clinical implications
NGT feeding under restraint is not uncommon in England, with variation in implementation. Further research is needed to understand how the high comorbidity and complexity contribute to initiation and termination of the intervention.
OBJECTIVES/GOALS: Greater blood pressure (BP) reactivity and socioeconomic deprivation (e.g., area deprivation index; ADI) are associated with poor vascular health [1-3]. However, it is unclear if ADI is associated with BP reactivity. Thus, we sought to examine if ADI is associated with BP reactivity in young adults. METHODS/STUDY POPULATION: Participants completed questionnaires used to derive lifetime ADI averaged from early-, mid-childhood, and adolescence. Participants completed a handgrip (HG) exercise protocol including 10 minutes of rest, 2 minutes of static HG at 40% of their maximal voluntary contraction, 3 minutes of post-exercise ischemia (PEI), and 2 minutes of recovery (REC). Beat-to-beat BP (photoplethysmography) and heartrate (HR; electrocardiogram) were continually assessed. We used the Shapiro-Wilk test to assess data for normality. We examined associations between ADI, BP reactivity, and HR using unadjusted and body mass index (BMI), sex, and race-adjusted Pearson’s correlation (set a priori to 0.05). RESULTS/ANTICIPATED RESULTS: This study included 53 (27Males/26Females; 21 ± 1 years; 24Black/29White; BP 107 ± 9/64 ± 9 mmHg) participants. There were racial differences (Black compared to White adults) for several BP reactivity metrics (e.g., PEI minute 3 diastolic BP: 96 ± 15 vs. 84 ± 19 mmHg, p=0.014) and lifetime ADI (p0.050). DISCUSSION/SIGNIFICANCE: Our data suggest racial differences exist in socioeconomic deprivation in a modestly sized young adult sample living in the southeast. While additional data are needed for other stressors, socioeconomic deprivation was not independently associated with BP or HR reactivity during acute exercise.
The cornerstone of obesity treatment is behavioural weight management, resulting in significant improvements in cardio-metabolic and psychosocial health. However, there is ongoing concern that dietary interventions used for weight management may precipitate the development of eating disorders. Systematic reviews demonstrate that, while for most participants medically supervised obesity treatment improves risk scores related to eating disorders, a subset of people who undergo obesity treatment may have poor outcomes for eating disorders. This review summarises the background and rationale for the formation of the Eating Disorders In weight-related Therapy (EDIT) Collaboration. The EDIT Collaboration will explore the complex risk factor interactions that precede changes to eating disorder risk following weight management. In this review, we also outline the programme of work and design of studies for the EDIT Collaboration, including expected knowledge gains. The EDIT studies explore risk factors and the interactions between them using individual-level data from international weight management trials. Combining all available data on eating disorder risk from weight management trials will allow sufficient sample size to interrogate our hypothesis: that individuals undertaking weight management interventions will vary in their eating disorder risk profile, on the basis of personal characteristics and intervention strategies available to them. The collaboration includes the integration of health consumers in project development and translation. An important knowledge gain from this project is a comprehensive understanding of the impact of weight management interventions on eating disorder risk.
Clinicians working in mental health in-patient settings may have to use nasogastric tube feeding under physical restraint to reverse the life-threatening consequences of malnutrition when this is driven by a psychiatric condition such as a restrictive eating disorder.
Aims
To understand the decision-making process when nasogastric tube feeding under restraint is initiated in mental health in-patient settings.
Method
People with lived experience of nasogastric tube feeding under restraint and parents/carers were recruited via the website of the UK's eating disorder charity BEAT. Eating disorder clinicians were recruited via an online post by the British Eating Disorders Society. Semi-structured interviews were administered to all participants.
Results
Themes overlapped between the participant groups and were integrated in the final analysis. Two main themes were generated: first, ‘quick decisions’, with the subthemes of ‘medical risk’, ‘impact of not eating’ and ‘limited discussions’; second, ‘slow decisions’, with subthemes of ‘threats’, ‘discussions with patient’, ‘not giving up’ and ‘advanced directives’. Benefits and harms of both quick and slow decisions were identified.
Conclusions
This research offers a new perspective regarding how clinical teams can make best practice decisions regarding initiating nasogastric feeding under restraint. In-patient mental health teams facilitating this clinical intervention should consider discussing it with the patient at the beginning of their admission in anticipation of the need for emergency intervention and in full collaboration with the multidisciplinary team.
Tungsten (W) films have many applications in the semiconducting industry for sensor technology. Deposition conditions can significantly impact the resulting W films in terms of the phases present (α-BCC or β-A12), microstructural grain orientation (texture), and residual strain. Tilt-A-Whirl methodology has been employed for the evaluation of a W film showing both texture and residual strain. Sin2(ψ) analysis of the film was performed to quantify the strongly tensile in-plane strain (+0.476%) with an estimated in-plane tensile stress of ~1.9 GPa. The 3D dataset was also evaluated qualitatively via 3D visualization. Visualization of 3D texture/strain data poses challenges due to peak broadening resulting from defocusing of the beam at high ψ tilt angles. To address this issue, principal component analysis (PCA) was employed to diagnose, model, and remove the broadening component from the diffraction data. Evaluation of the raw data and subsequent corrected data (after removal of defocusing effects) has been performed through projection of the data into a virtual 3D environment (via CAD2VR software) to qualitatively detect the impact of residual strain on the observed pole figure.
There is significant interest in developing early passage cell lines with matched normal reference DNA to facilitate a precision medicine approach in assessing drug response. This study aimed to establish early passage cell lines, and perform whole exome sequencing and short tandem repeat profiling on matched normal reference DNA, primary tumour and corresponding cell lines.
Methods
A cell culture based, in vitro study was conducted of patients with primary human papillomavirus positive and human papillomavirus negative tumours.
Results
Four early passage cell lines were established. Two cell lines were human papillomavirus positive, confirmed by sequencing and p16 immunoblotting. Short tandem repeat profiling confirmed that all cell lines were established from their index tumours. Whole exome sequencing revealed that the matched normal reference DNA was critical for accurate mutational analysis: a high rate of false positive mutation calls were excluded (87.6 per cent).
Conclusion
Early passage cell lines were successfully established. Patient-matched reference DNA is important for accurate cell line mutational calls.
To determine the prevalence of human papillomavirus in paediatric tonsils in Southwestern Ontario, Canada.
Materials and methods
Patients aged 0–18 years undergoing tonsillectomy were recruited. Two specimens (left and right tonsils) were collected from each participant. Tonsillar DNA was analysed using quantitative polymerase chain reaction to determine the presence of human papillomavirus subtypes 6, 11, 16 or 18.
Results
A total of 102 patients, aged 1–18 years (mean age of 5.7 years), were recruited. Ninety-nine surveys were returned. There were 44 females (44.4 per cent) and 55 males (55.6 per cent). Forty patients (40.4 per cent) were firstborn children and 73 (73.7 per cent) were delivered vaginally. Six mothers (6.1 per cent) and one father (1.0 per cent) had prior known human papillomavirus infection, and one mother (1.0 per cent) had a history of cervical cancer. All tonsil specimens were negative for human papillomavirus subtypes 6, 11, 16 and 18.
Conclusion
No human papillomavirus subtypes 6, 11, 16 or 18 were found in paediatric tonsil specimens from Southwestern Ontario.
Evidence suggests that pregnant women who test positive for COVID-19 may develop more severe illness than non-pregnant women and may be at greater risk for psychological distress. The relationship between COVID-19 status (positive, negative, never tested) and symptoms of depression was examined in a survey study (May to September 2020) of pregnant women (n = 869). Pregnant women who reported testing positive for COVID-19 were significantly more likely to report depressive symptoms compared with women who tested negative (P = 0.027) and women who were never tested (P = 0.005). Findings indicate that pregnant women who test positive for COVID-19 should be screened and monitored for depressive symptoms.