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Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
In this retrospective cohort study of military trainees, symptomatic-only coronavirus disease 2019 (COVID-19) arrival antigen testing decreased isolation requirements without increasing secondary cases compared to universal antigen testing. Symptomatic-only arrival antigen testing is a feasible alternative for individuals entering a congregant setting with a high risk of COVID-19 transmission.
Immediate-use steam sterilization (IUSS) shortens the time of sterilization but may increase the risk of surgical site infection (SSI). Among 23,919 procedures with 416 (1.7%) procedures resulting in SSI, IUSS was associated with a 1.52 (95% CI, 1.10–2.11) times higher risk of SSI. IUSS should be minimized.
Depression is a major cause of disability world-wide. Up to a third of patients have a treatment-resistant form (TRD), presenting a major challenge. Ketamine has been introduced as a novel rapid-acting antidepressant effective in this population. However, at present, ketamine treatment is not routinely informed by any objective neural markers. Basic research has shown promising electroencephalogram (EEG) changes including a decrease in alpha power. However, clinical translation is lacking.
Objectives
Assess the feasibility of identifying EEG correlates of ketamine infusions in a routine outpatient setting with a low-cost, easily usable system.
Methods
The study was carried out at the Oxford Health Foundation Trust Ketamine Clinic (ethics reference 22/EM/0226). N=18 EEG recordings from N=12 patients were collected (5 women, mean age 44, range 33-62, IV dose 0.5-1mg/kg over 40min). 4-channel EEG was collected with a Muse-S headband at 256Hz, from 5min before to 55min after infusion start. 5s epochs were rejected if gyroscope data indicated head movement above 10 deg/s or if amplitude was above 200μV. A spectrogram (4s window, 3s overlap) as well as band-limited power (theta: 4-8Hz, alpha: 8-13Hz, beta: 13-25Hz) were computed. Significance of changes was found with a repeated measures analysis of variance (RM-ANOVA) on power in 5min segments together with post-hoc Tukey’s P-values.
Results
Across the ketamine infusion recordings, there was a significant effect of time (F=3.65, P=0.0105) and Channel*Time interaction (F=3.80, P<0.001) on the EEG spectrum. Effects were largest on temporal electrodes, particularly TP9 in the alpha and theta bands (Figure 1, Table 1).Table 1:
Effect sizes (Cohen’s d) and FDR-corrected ANOVA P-values for ketamine effects on each EEG channel and frequency band. P<0.05 was considered significant (bold). n.s. = not significant (P>0.2).
Channel / Band
TP9
AF7
AF8
TP10
Theta
1.16 (P=0.019)
0.11 (n.s.)
0.11 (n.s.)
0.42 (P=0.113)
Alpha
1.41 (P<0.001)
0.12 (n.s.)
0.17 (n.s.)
0.605 (P=0.113)
Beta
1.19 (P=0.112)
0.03 (n.s.)
0.08 (n.s.)
0.21 (n.s.)
Image:
Conclusions
In a routine outpatient setting, sub-anaesthetic ketamine infusions in TRD patients were associated with decreased fronto-temporal EEG alpha and theta power. Future work should assess the potential of low-cost routine EEG, and alpha desaturation specifically, to inform individualised ketamine treatment.
Providing access to food in schools can serve as a platform for food system transformation, while simultaneously improving educational outcomes and livelihoods. Locally grown and procured food is a nutritious, healthy, and efficient way to provide schoolchildren with a daily meal while, at the same time, improving opportunities for smallholder farmers(1). While there is significant potential for school food provision activities to support healthy dietary behaviours in the Pacific Islands region, there is limited evidence of these types of activities(2), including scope and links to local food production in the region. Therefore, the aim of this scoping study was to understand the current state of school food activities (school feeding, gardening and other food provision activities) and any current, and potential links to local agriculture in the Pacific Islands. A regional mapping activity was undertaken, initially covering 22 Pacific Island countries. The mapping included two steps: 1) a desk based scoping review including peer-reviewed and grey literature (2007-2022) and 2) One-hour semi-structured online Zoom interviews with key country stakeholders. Twelve sources were identified, predominately grey literature (n = 9). Thirty interviews were completed with at least 1 key stakeholder from 15 countries. A variety of school food provision activities were identified, including school feeding programs (n = 16, of varying scale), programs covering both school feeding and school gardens (n = 2), school garden programs (n = 12), and other school food provision activities (n = 4, including taste/sensory education, food waste reduction, increasing canteen capacity for local foods, supply chain distribution between local agriculture and schools). Existing links to local agriculture varied for the different programs. Of the 16 school feeding programs, 8 had a requirement for the use of local produce (policy requirement n = 6, traditional requirement from leaders n = 2). Of the 12 school garden programs, 6 used local or traditional produce in the garden and 5 involved local farmers in varying capacities. Challenges to linking local agriculture into school food provision programs were reported for 17 activities and were context dependent. Common challenges included limited funding, inflation, Covid-19, inadequate produce supply for the scale of program, limited farmer capacity, limited institutional support for local produce, low produce storage life, climatic conditions and disasters, water security, delayed procurement process, and limited professional development and upskilling opportunities. Modernisation and colonisation of food systems resulting in a preference for hyperpalatable foods and challenges in incorporating local produce in a way that is accepted by students was also identified as a challenge. This evidence can be used to develop a pathway to piloting and implementing models of school food provision programs and promoting opportunities for shared learning and collaboration with key stakeholders across the Pacific Islands region.
At least 200 billion black soldier fly (Hermetia illucens) larvae (BSFL) are reared each year as food and feed, and the insect farming industry is projected to grow rapidly. Despite interest by consumers, producers, and legislators, no empirical evidence exists to guide producers in practicing humane – or instantaneous – slaughter for these novel mini-livestock. BSFL may be slaughtered via freezing, boiling, grinding, or other methods; however standard operating procedures (SOPs) and equipment design may affect the likelihood of instantaneous death using these methods. We tested how larval body size and particle size plate hole diameter affect the likelihood of instantaneous death for black soldier fly larvae that are slaughtered using a standard meat grinder. Larval body size did not affect the likelihood of instantaneous death for larvae that are 106–175 mg in mass. However, particle size plate hole diameter had a significant effect on the likelihood of instantaneous death, with only 54% of larvae experiencing an instant death when using the largest particle size plate (12-mm hole diameter) compared to 84% using the smallest particle size plate (2.55 mm). However, a higher percentage of instantaneous death (up to 99%) could be achieved by reducing the proportion of larvae that become stuck in the machine. We conclude by outlining specific recommendations to support producers in achieving a 99% instantaneous death rate through specific SOPs to be used with similarly designed machines. We also develop a protocol for producers that wish to test their own grinding SOPs.
Sleep has been shown to directly impact cognitive function throughout the lifespan; good quality sleep benefits and improves cognitive function, including processing speed and attention, while poor quality sleep can contribute to negative cognitive outcomes1. In particular, attention, learning, and memory have been demonstrated to be sensitive to sleeping changes, including fragmentation and restriction2. Subjective sleeping scales are utilized in both research and clinical practice, allowing sleep to be measured via self-report on various domains, including duration and factors that can contribute to sleep disruption and disturbances3. This study aims to examine the possible relation between subjective sleep quality and cognitive function among middle-aged adults to inform future research for early interventions of modifiable behaviors that can contribute to abnormal cognitive decline.
Participants and Methods:
Data for this analysis is part of the preliminary results of an ongoing pilot study. 29 middle-aged (40-65 years, inclusive), cognitively unimpaired individuals were recruited from the community. Subjective sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Attention and memory were measured using the California Verbal Learning Test, Third Edition (CVLT-III).
Results:
Multiple hierarchical regression analyses were conducted to evaluate if aspects of sleep quality were significantly correlated to complex attention and learning performance in this sample. First, correlation amylases showed significant relationships between PSQI Component 6 (Use of Sleeping Medication) and Trials 1 to 2 Learning Slope (R2 = -0.56, p =0.002) and CVLT-III Trials 1 through 5 Recall Discriminability (R2 = -0.42, p = 0.02), each with significant regression analyses outcomes (b =0.42, p = 0.04 and b = -0.46, p = 0.04, respectively). There were other variables that were found to be significantly correlated; however, after adjusting for relevant demographic variables (age, education, sex), the hierarchical regression analyses revealed no association between the aforementioned variables.
Conclusions:
While multiple aspects of sleep quality were expected to influence measures of attention and learning, only PSQI Component 6 was found to be statistically significantly associated with only two learning variables. Limitations of this study included a small sample size which was limited to cognitive and relatively physically healthy middle-aged adults. Further, sleep quality was measured with one subjective measure and no objective data was collected to support the hypotheses. Future analysis is needed to continue to explore the relation between subjective sleep quality and cognitive outcomes. As this is an ongoing study, we look forward to exploring this research question in more detail as the study progresses.
We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England.
Methods
108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models.
Results
Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71–0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74–0.87, p < 0.0001). Referral to substance use services and ‘other’ services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78–0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79–0.94, p = 0.001).
Conclusions
SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.
The relationship between dietary habits and microbiota composition during adolescence has not been well examined. This is a crucial knowledge gap to fill considering that diet–microbiota interactions influence neurodevelopment, immune system maturation and metabolic regulation. This study examined the associations between diet and the gut microbiota in a school-based sample of 136 adolescents (Mage = 12·1 years; age range 11–13 years; 48 % female; 47 % Black, 38 % non-Hispanic White, 15 % Hispanic or other minorities) from urban, suburban and rural areas in the Southeast USA. Adolescents completed the Rapid Eating Assessment for Participants and provided stool samples for 16S ribosomal RNA gene sequencing. Parents reported their child and family socio-demographic characteristics. The associations between diet and socio-demographics with gut microbiota diversity and abundance were analysed using multivariable regression models. Child race and ethnicity, sex, socio-economic status and geographic locale contributed to variation within microbiota composition (β-diversity). Greater consumption of processed meat was associated with a lower microbial α-diversity after adjusting for socio-demographic variables. Multi-adjusted models showed that frequent consumption of nutrient-poor, energy-dense foods (e.g. sugar-sweetened beverages, fried foods, sweets) was negatively associated with abundances of genera in the family Lachnospiraceae (Anaerostipes, Fusicatenibacter and Roseburia), which are thought to play a beneficial role in host health through their production of short-chain fatty acids (SCFAs). These results provide new insights into the complex relationships among socio-demographic factors, diet and gut microbiota during adolescence. Adolescence may represent a critical window of opportunity to promote healthy eating practices that shape a homoeostatic gut microbiota with life-long benefits.
Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.
To evaluate the impact of a diagnostic stewardship intervention on Clostridioides difficile healthcare-associated infections (HAI).
Design:
Quality improvement study.
Setting:
Two urban acute care hospitals.
Interventions:
All inpatient stool testing for C. difficile required review and approval prior to specimen processing in the laboratory. An infection preventionist reviewed all orders daily through chart review and conversations with nursing; orders meeting clinical criteria for testing were approved, orders not meeting clinical criteria were discussed with the ordering provider. The proportion of completed tests meeting clinical criteria for testing and the primary outcome of C. difficile HAI were compared before and after the intervention.
Results:
The frequency of completed C. difficile orders not meeting criteria was lower [146 (7.5%) of 1,958] in the intervention period (January 10, 2022–October 14, 2022) than in the sampled 3-month preintervention period [26 (21.0%) of 124; P < .001]. C. difficile HAI rates were 8.80 per 10,000 patient days prior to the intervention (March 1, 2021–January 9, 2022) and 7.69 per 10,000 patient days during the intervention period (incidence rate ratio, 0.87; 95% confidence interval, 0.73–1.05; P = .13).
Conclusions:
A stringent order-approval process reduced clinically nonindicated testing for C. difficile but did not significantly decrease HAIs.
We examine the Holocene loess record in the Heye Catchment on the margins of the Tibetan Plateau (TP) and China Loess Plateau (CLP) to determine: the region to which the Heye Catchment climate is more similar; temporal change in wind strength; and modification of the loess record by mass wasting and human activity. Luminescence and radiocarbon dating demonstrate loess deposited in two periods: >11–8.6 ka and <5.1 ka. The 8.6–5.1 ka depositional hiatus, which coincides with the Mid-Holocene Climatic Optimum, is more similar to the loess deposition cessation in the TP than to the loess deposition deceleration in the CLP. Grain-size analysis suggests the Heye loess is a mixture of at least three different grain-size distributions and that it may derive from multiple sources. A greater proportion of coarse sediments in the older loess may indicate stronger winds compared with the more recent depositional period. Gravel incorporated into younger loess most likely comes from bedrock exposed in slump scarps. Human occupation of the catchment, for which the earliest evidence is 3.4 ka, postdates the onset of slumping; thus the slumps may have created a livable environment for humans.
Many graduate programs are sincerely invested in fostering diversity and increasing the number of students from underrepresented backgrounds who will contribute to our discipline.But increasing representation is only one step needed to address inequities, disparities, and injustices.Helping all students thrive, and have an equal opportunity to achieve their educational goals requires the creation of “safe spaces” in which demographic differences are understood, appreciated, and considered in larger educational systems.This chapter discusses a frequently overlooked identity characteristic that can significantly impact the graduate school experience:being a first-generation college student.
Trends suggest that a substantial and increasing number of psychology students are working in post-baccalaureate (post-bacc) research assistant (RA) positions to gain additional experience prior to applying to graduate programs. However, few resources exist to guide students in pursuing RA positions and making the most of them. This chapter reviews factors to consider when determining whether to pursue a post-bacc RA position, provides guidance for finding and obtaining these positions, and shares suggestions for how to best prepare for graduate school during the post-bacc years. A comparison of the unique training and professional development opportunities afforded by volunteer and paid RA positions is provided, and participation in national and regional psychology conferences is emphasized.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
This paper presents the first records of the brittle star Ophiactis abyssicola in Canadian waters and range extensions of up to 1900 km in the Northwest Atlantic from previously known locations. Samples were collected off northern Labrador and the northern portion of insular Newfoundland (eastern Canada) at 433 and 1097 m depths, respectively. This newly recorded species of brittle star from the bathyal zone off Newfoundland and Labrador adds to the marine biodiversity of Canada and to the general distribution knowledge of O. abyssicola.
Nucleated red blood cells (NRBCs) are immature red cells that under normal conditions are not present in the peripheral circulation. Several studies have suggested an association between elevated NRBC and poor outcome in critically ill adults and neonates. We sought to determine if elevations in NRBC value following cardiac surgery and following clinical events during the hospital stay can be used as a biomarker to monitor for mortality risk in neonates post-cardiac surgery.
Materials and methods:
We constructed a retrospective study of 264 neonates who underwent cardiac surgery at Children’s Hospital, New Orleans between 2011 and 2020. Variables included mortality and NRBC value were recorded following cardiac surgery and following peri-operative clinical events. The study was approved by LSU Health IRB. Sensitivity, specificity, receiver operating characteristic (ROC) curves with area under the curve (AUC) and logistic regression analysis were performed.
Results:
Thirty-six patients (13.6%) died, of which 32 had an NRBC value ≥10/100 white blood cell (WBC) during hospitalisation. Multi-variable analysis found extracorporeal membrane oxygenation use (OR 10, 95% CI 2.9–33, p=<0.001), NRBC ≥10/100 WBC (OR 16.1, CI 4.1–62.5, p ≤ 0.001) and peak NRBC in the 14-day period post-cardiac surgery (continuous variable, OR 1.05, 95% CI 1.0–1.09, p = 0.03), to be independently associated with mortality. Using a cut-off NRBC value of 10/100 WBC, there was an 88.9% sensitivity and a 90.8% specificity, with ROC curve showing an AUC of 0.9 and 0.914 for peak NRBC value in 14 days post-surgery and entire hospitalisation, respectively.
Conclusions:
NRBC ≥10/100 WBC post-cardiac surgery is strongly associated with mortality. Additionally, NRBC trend appears to show promise as an accurate biomarker for mortality.
Understanding the effects of acute feeding on body composition and metabolic measures is essential to the translational component and practical application of measurement and clinical use. To investigate the influence of acute feeding on the validity of dual-energy X-ray absorptiometry (DXA), a four-compartment model (4C) and indirect calorimetry metabolic outcomes, thirty-nine healthy young adults (n 19 females; age: 21·8 (sd 3·1) years, weight; 71·5 (sd 10·0) kg) participated in a randomised cross-over study. Subjects were provided one of four randomised meals on separate occasions (high carbohydrate, high protein, ad libitum or fasted baseline) prior to body composition and metabolic assessments. Regardless of macronutrient content, acute feeding increased DXA percent body fat (%fat) for the total sample and females (average constant error (CE):–0·30 %; total error (TE): 2·34 %), although not significant (P = 0·062); the error in males was minimal (CE: 0·11 %; TE: 0·86 %). DXA fat mass (CE: 0·26 kg; TE: 0·75 kg) and lean mass (LM) (CE: 0·83 kg; TE: 1·23 kg) were not altered beyond measurement error for the total sample. 4C %fat was significantly impacted from all acute feedings (avg CE: 0·46 %; TE: 3·7 %). 4C fat mass (CE: 0·71 kg; TE: 3·38 kg) and fat-free mass (CE: 0·55 kg; TE: 3·05 kg) exceeded measurement error for the total sample. RMR was increased for each feeding condition (TE: 1666·9 kJ/d; 398 kcal/d). Standard pre-testing fasting guidelines may be important when evaluating DXA and 4C %fat, whereas additional DXA variables (fat mass and LM) may not be significantly impacted by an acute meal. Measuring body composition via DXA under less stringent pre-testing guidelines may be valid and increase feasibility of testing in clinical settings.
Adolescent risk for self-injurious thoughts and behaviors (STBs) involves disturbance across multiple systems (e.g., affective valence, arousal regulatory, cognitive and social processes). However, research integrating information across these systems is lacking. Utilizing a multiple-levels-of-analysis approach, this person-centered study identified psychobiological stress response profiles and linked them to cognitive processes, interpersonal behaviors, and STBs. At baseline, adolescent girls (N = 241, Mage = 14.68 years, Range = 12–17) at risk for STBs completed the Trier Social Stress Test (TSST), questionnaires, and STB interviews. Positive affect (PA), negative affect (NA), and salivary cortisol (SC) were assessed before and after the TSST. STBs were assessed again during 3, 6, and 9 month follow-up interviews. Multitrajectory modeling of girls’ PA, NA, and SC revealed four profiles, which were compared on cognitive and behavioral correlates as well as STB outcomes. Relative to normative, girls in the affective distress, hyperresponsive, and hyporesponsive subgroups were more likely to report negative cognitive style (all three groups) and excessive reassurance seeking (hyporesponsive only) at baseline, as well as nonsuicidal self-injury (all three groups) and suicidal ideation and attempt (hyporesponsive only) at follow-up. Girls’ close friendship characteristics moderated several profile–STB links. A synthesis of the findings is presented alongside implications for person-centered tailoring of intervention efforts.