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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.
Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
This review aims to highlight the relative importance of cardiovascular disease (CVD) lifestyle-associated risk factors among individuals with inflammatory bowel disease (IBD) and examine the effectiveness of lifestyle interventions to improve these CVD risk factors. Adults with IBD are at higher risk of CVD due to systemic and gut inflammation. Besides that, tobacco smoking, dyslipidaemia, hypertension, obesity, physical inactivity and poor diet can also increase CVD risk. Typical IBD behavioural modification including food avoidance and reduced physical activity, as well as frequent corticosteroid use, can further increase CVD risk. We reviewed seven studies and found that there is insufficient evidence to conclude the effects of diet and/or physical activity interventions on CVD risk outcomes among populations with IBD. However, the limited findings suggest that people with IBD can adhere to a healthy diet or Mediterranean diet (for which there is most evidence) and safely participate in moderately intense aerobic and resistance training to potentially improve anthropometric risk factors. This review highlights the need for more robust controlled trials with larger sample sizes to assess and confirm the effects of lifestyle interventions to mitigate modifiable CVD risk factors among the IBD population.
Reducing inequalities in preconception health and care is critical to improving the health and life chances of current and future generations. A hybrid workshop was held at the 2023 UK Preconception Early and Mid-Career Researchers (EMCR) Network conference to co-develop recommendations on ways to address inequalities in preconception health and care. The workshop engaged multi-disciplinary professionals across diverse career stages and people with lived experience (total n = 69). Interactive discussions explored barriers to achieving optimal preconception health, driving influences of inequalities and recommendations. The Socio-Ecological Model framed the identified themes, with recommendations structured at interpersonal (e.g. community engagement), institutional (e.g. integration of preconception care within existing services) and environmental/societal levels (e.g. education in schools). The co-developed recommendations provide a framework for addressing inequalities in preconception health, emphasising the importance of a whole-systems approach. Further research and evidence-based interventions are now needed to advance the advocacy and implementation of our recommendations.
Globally, mental disorders account for almost 20% of disease burden and there is growing evidence that mental disorders are associated with various social determinants. Tackling the United Nations Sustainable Development Goals (UN SDGs), which address known social determinants of mental disorders, may be an effective way to reduce the global burden of mental disorders.
Objectives
To examine the evidence base for interventions that seek to improve mental health through targeting the social determinants of mental disorders.
Methods
We conducted a systematic review of reviews, using a five-domain conceptual framework which aligns with the UN SDGs (PROSPERO registration: CRD42022361534). PubMed, PsycInfo, and Scopus were searched from 01 January 2012 until 05 October 2022. Citation follow-up and expert consultation were used to identify additional studies. Systematic reviews including interventions seeking to change or improve a social determinant of mental disorders were eligible for inclusion. Study screening, selection, data extraction, and quality appraisal were conducted in accordance with PRISMA guidelines. The AMSTAR-2 was used to assess included reviews and results were narratively synthesised.
Results
Over 20,000 records were screened, and 101 eligible reviews were included. Most reviews were of low, or critically low, quality. Reviews included interventions which targeted sociocultural (n = 31), economic (n = 24), environmental (n = 19), demographic (n = 15), and neighbourhood (n = 8) determinants of mental disorders. Interventions demonstrating the greatest promise for improved mental health from high and moderate quality reviews (n = 37) included: digital and brief advocacy interventions for female survivors of intimate partner violence; cash transfers for people in low-middle-income countries; improved work schedules, parenting programs, and job clubs in the work environment; psychosocial support programs for vulnerable individuals following environmental events; and social and emotional learning programs for school students. Few effective neighbourhood-level interventions were identified.
Conclusions
This review presents interventions with the strongest evidence base for the prevention of mental disorders and highlights synergies where addressing the UN SDGs can be beneficial for mental health. A range of issues across the literature were identified, including barriers to conducting randomised controlled trials and lack of follow-up limiting the ability to measure long-term mental health outcomes. Interdisciplinary and novel approaches to intervention design, implementation, and evaluation are required to improve the social circumstances and mental health experienced by individuals, communities, and populations.
Marine litter poses a complex challenge in Indonesia, necessitating a well-informed and coordinated strategy for effective mitigation. This study investigates the seasonality of plastic concentrations around Sulawesi Island in central Indonesia during monsoon-driven wet and dry seasons. By using open data and methodologies including the HYCOM and Parcels models, we simulated the dispersal of plastic waste over 3 months during both the southwest and northeast monsoons. Our research extended beyond data analysis, as we actively engaged with local communities, researchers and policymakers through a range of outreach initiatives, including the development of a web application to visualize model results. Our findings underscore the substantial influence of monsoon-driven currents on surface plastic concentrations, highlighting the seasonal variation in the risk to different regional seas. This study adds to the evidence provided by coarser resolution regional ocean modelling studies, emphasizing that seasonality is a key driver of plastic pollution within the Indonesian archipelago. Inclusive international collaboration and a community-oriented approach were integral to our project, and we recommend that future initiatives similarly engage researchers, local communities and decision-makers in marine litter modelling results. This study aims to support the application of model results in solutions to the marine litter problem.
We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.
Methods
We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.
Results
The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).
Conclusions
The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.
Two rapid methods for the decomposition and chemical analysis of clays were adapted for use with 20–40-mg size samples, typical amounts of ultrafine products (<0.5-μm diameter) obtained by modern separation methods for clay minerals. The results of these methods were compared with those of “classical” rock analyses. The two methods consisted of mixed lithium metaborate fusion and heated decomposition with HF in a closed vessel. The latter technique was modified to include subsequent evaporation with concentrated H2SO4 and re-solution in HCl, which reduced the interference of the fluoride ion in the determination of Al, Fe, Ca, Mg, Na, and K. Results from the two methods agree sufficiently well with those of the “classical” techniques to minimize error in the calculation of clay mineral structural formulae. Representative maximum variations, in atoms per unit formula of the smectite type based on 22 negative charges, are 0.09 for Si, 0.03 for Al, 0.015 for Fe, 0.07 for Mg, 0.03 for Na, and 0.01 for K.
Odd Radio Circles (ORCs) are a class of low surface brightness, circular objects approximately one arcminute in diameter. ORCs were recently discovered in the Australian Square Kilometre Array Pathfinder (ASKAP) data and subsequently confirmed with follow-up observations on other instruments, yet their origins remain uncertain. In this paper, we suggest that ORCs could be remnant lobes of powerful radio galaxies, re-energised by the passage of a shock. Using relativistic hydrodynamic simulations with synchrotron emission calculated in post-processing, we show that buoyant evolution of remnant radio lobes is alone too slow to produce the observed ORC morphology. However, the passage of a shock can produce both filled and edge-brightnened ORC-like morphologies for a wide variety of shock and observing orientations. Circular ORCs are predicted to have host galaxies near the geometric centre of the radio emission, consistent with observations of these objects. Significantly offset hosts are possible for elliptical ORCs, potentially causing challenges for accurate host galaxy identification. Observed ORC number counts are broadly consistent with a paradigm in which moderately powerful radio galaxies are their progenitors.
Almaatouq et al. propose an integrative experiment design space combined with large samples for scientific advancement. We argue recent innovative designs combining closed-loop experiment designs and Bayesian optimisation allow for integrative experiments at an individual level during a single session, circumventing the necessity for large samples. This method can be applied across disciplines, including developmental and clinical research.
We present and evaluate the prospects for detecting coherent radio counterparts to gravitational wave (GW) events using Murchison Widefield Array (MWA) triggered observations. The MWA rapid-response system, combined with its buffering mode ($\sim$4 min negative latency), enables us to catch any radio signals produced from seconds prior to hours after a binary neutron star (BNS) merger. The large field of view of the MWA ($\sim$$1\,000\,\textrm{deg}^2$ at 120 MHz) and its location under the high sensitivity sky region of the LIGO-Virgo-KAGRA (LVK) detector network, forecast a high chance of being on-target for a GW event. We consider three observing configurations for the MWA to follow up GW BNS merger events, including a single dipole per tile, the full array, and four sub-arrays. We then perform a population synthesis of BNS systems to predict the radio detectable fraction of GW events using these configurations. We find that the configuration with four sub-arrays is the best compromise between sky coverage and sensitivity as it is capable of placing meaningful constraints on the radio emission from 12.6% of GW BNS detections. Based on the timescales of four BNS merger coherent radio emission models, we propose an observing strategy that involves triggering the buffering mode to target coherent signals emitted prior to, during or shortly following the merger, which is then followed by continued recording for up to three hours to target later time post-merger emission. We expect MWA to trigger on $\sim$$5-22$ BNS merger events during the LVK O4 observing run, which could potentially result in two detections of predicted coherent emission.
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.
Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone.
Aims
To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone).
Method
In a 4-week, three-arm, ‘double dummy’ trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure.
Results
This trial will advance the understanding of psilocybin's mechanism of antidepressant action.
Conclusions
This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.
The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS).
Method:
The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery was used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data.
Results:
For the eight domains of cognitive functioning identified (orientation, memory [immediate, delayed, and recognition], set shifting, attention/speed, language/fluency, and visuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where fit must be perfect and is not informative. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94).
Conclusions:
The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used to operationalize notions of neurocognitive impairment, and as a starting point for prioritizing pre-statistical harmonization and evaluating configural invariance in cross-national research.
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
Methods
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Results
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Conclusions
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
We present the Cosmological Double Radio Active Galactic Nuclei (CosmoDRAGoN) project: a large suite of simulated AGN jets in cosmological environments. These environments sample the intra-cluster media of galaxy clusters that form in cosmological smooth particle hydrodynamics (SPH) simulations, which we then use as inputs for grid-based hydrodynamic simulations of radio jets. Initially conical jets are injected with a range of jet powers, speeds (both relativistic and non-relativistic), and opening angles; we follow their collimation and propagation on scales of tens to hundreds of kiloparsecs, and calculate spatially resolved synthetic radio spectra in post-processing. In this paper, we present a technical overview of the project, and key early science results from six representative simulations which produce radio sources with both core- (Fanaroff-Riley Type I) and edge-brightened (Fanaroff-Riley Type II) radio morphologies. Our simulations highlight the importance of accurate representation of both jets and environments for radio morphology, radio spectra, and feedback the jets provide to their surroundings.
Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, “Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease,” includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.
Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.
Aims
Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Method
Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).
Results
Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.
Conclusions
Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
Animal welfare is of increasing significance for European consumers and citizens. Previously, agricultural production focused mainly on supply, price and competition but consumers now expect their food to be produced and processed with greater respect for the welfare of the animals. Food quality is therefore determined by the welfare status of the animals from which it was produced as well as the nature and safety of the end product. Thus, practical welfare improvement strategies and reliable on-farm monitoring systems for assessing the animals’ welfare status and evaluating potential risks are urgently required to accommodate societal concerns and market demands. It is also of paramount importance to define the kind of information that consumers want about the final products and to develop effective strategies for communicating welfare standards to the public. Generating an intensified dialogue with all factions of society on welfare issues as well as appropriate labelling of animal products and farming systems that offer guarantees about welfare issues and production conditions will, in turn, promote transparency and the societal sustainability of European agriculture. Welfare is multidimensional. It cannot be measured directly but only inferred from external parameters. Therefore, the integration of the most appropriate specialist expertise in Europe is essential to develop, refine, standardise and intercalibrate welfare monitoring systems and to identify and validate remedial measures. We must establish a European standard for welfare assessment systems in order to facilitate intra-European trade and marketing. Only then can we harmonise labelling that is informative and relevant to all European consumers.