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.

A Bi-factor analysis is made of Professor Thurstone's battery of fifty-seven tests employing his tetrachoric correlations. Although this analysis is made entirely independent of his multiple factor analysis, a very close agreement is found between the group factors obtained here and Thurstone's verbal descriptions previously published.

Phylloblastia iranica S. Kazemi, Lücking & Sipman sp. nov. is described and illustrated as a new foliicolous lichen. It is characterized by 1-septate, colourless, more or less fusiform, slightly curved ascospores, 9–19 × 4–6 μm. In addition, the foliicolous Strigula buxi Chodat is reported for the first time from Iran, increasing the number of foliicolous lichens known from that country to three, where previously only Gyalectidium caucasicum (Elenk. & Woron.) Vězda was recorded. All three species were found in boxwood (Buxus sempervirens) forest. A key to all known Phylloblastia species worldwide is provided.

This paper examines the population of corporate directors of Britain at the turn of the twentieth century. Over the period 1881-1911 the corporate form became the most common mode of business organisation for large businesses. As their number increased, the population of directors expanded and reflected an increasingly diversified corporate landscape. Based on a large-scale dataset, this paper analyses the characteristics and networks of this wider population of directors. The study goes beyond previous work, which has mainly focused on elite directors or prominent companies, and shows three key findings. First, the population of directors was very connected into a large network, complete isolation from this network was rare. Second, over 1881-1911 director interlocks with banks became less important for most sectors, while interlocks with other financial institutions such as trusts became increasingly important. Insurance companies stood out as the most connected sector spanning smaller local companies and larger international ones. Third, during the period studied there was a shift from director clusters that were mainly based on proximity, to those that were connected through industries.

The role of memory in supporting adolescents' sense of place and past is not well understood, but older adults offer a wealth of life stories and wisdom that they can share with younger generations. This in-depth pilot study positioned Australian high school students as oral historians to interview older Australians about their lives. Oral historian training and materials were provided, and pre- and post-intervention measures of adolescents' sense of everyday Australian history, well-being, and social connection were collected for an intervention school group (n = 17) and a waitlist control school group (n = 12). In-depth supplementary memory and well-being data were also collected for six participating older adults. In the intervention condition, scaffolded memory interviews took place during weekly aged care visits across one school term and were followed by an intergenerational celebration and memory book presentation. As hypothesised, older adults imbued their stories with life lessons for adolescents. Although no quantitative changes in participants' well-being emerged, qualitative data revealed the emergence of rich interpersonal relationships and bonding between adolescents and older adults. There were also benefits of the programme for older adults' reports of generativity and adolescents' understanding of everyday Australian history. The findings demonstrate the social and academic benefits of scaffolded intergenerational memory conversations and represent a scalable educational model and materials with downstream community benefits.

Globally, there is seasonal variation in tuberculosis (TB) incidence, yet the biological and behavioural or social factors driving TB seasonality differ across countries. Understanding season-specific risk factors that may be specific to the UK could help shape future decision-making for TB control. We conducted a time-series analysis using data from 152,424 UK TB notifications between 2000 and 2018. Notifications were aggregated by year, month, and socio-demographic covariates, and negative binomial regression models fitted to the aggregate data. For each covariate, we calculated the size of the seasonal effect as the incidence risk ratio (IRR) for the peak versus the trough months within the year and the timing of the peak, whilst accounting for the overall trend. There was strong evidence for seasonality (p < 0.0001) with an IRR of 1.27 (95% CI 1.23–1.30). The peak was estimated to occur at the beginning of May. Significant differences in seasonal amplitude were identified across age groups, ethnicity, site of disease, latitude and, for those born abroad, time since entry to the UK. The smaller amplitude in older adults, and greater amplitude among South Asians and people who recently entered the UK may indicate the role of latent TB reactivation and vitamin D deficiency in driving seasonality.

Dysregulation of immune responses results in the development of chronic inflammatory conditions. The current frontline therapy, glucocorticoids, are effective immunosuppressive drugs but come with a trade-off of cumulative, debilitating side effects with sustained use. Clearly, alternative drug options with improved safety profiles are urgently needed. Macrophage Migration Inhibitory Factor (MIF) is a pleotropic pro-inflammatory cytokine and integral component of immune and inflammatory responses. MIF counter-regulates the immunosuppressive effects of glucocorticoids and promotes NLRP3 inflammasome activation.1, 2 Elevated MIF is a feature of multiple diseases, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous. Given the association of increased MIF in serum with multiple disease models, it is considered MIF may be a plausible, specific druggable target in treatment of chronic inflammatory and autoimmune diseases, particularly as a target for glucocorticoid-sparing therapy to reduce the dose or duration of glucocorticoid treatment. The organosulfur isothiocyanate phytochemical sulforaphane (SFN) is extracted from cruciferous vegetables, including broccoli and Brussel sprouts following hydrolysis of its inactive precursor, glucoraphanin. SFN has antioxidant and cancer chemoprotective properties, and promotes NRF2 antioxidant signalling to upregulate the expression of numerous antioxidant enzymes. SFN has been shown to covalently modify MIF with high reactivity and is a potent inhibitor of MIF tautomerase activity. However, to date, no such study has evaluated the role of SFN as a novel inhibitor of MIF-mediated inflammatory pathway activation. Using cell-based assays, we have sought to investigate the role of SFN as an inhibitor of multiple inflammatory pathways which have previously implicated MIF as a possible regulator. Our initial work has examined SFN as an inhibitor of NF-κB activity, inflammasome activation, and evaluated if MIF is required for this effect. RAW264.7 murine macrophage cells stably expressing NF-κB-luciferase reporter construct were pre-treated with SFN (2.5 µM) before the induction of inflammation, via LPS (100ng/mL). For NLRP3 inflammasome activation, cells were subsequently treated with the NLRP3-specific inflammasome activator, nigericin (10 µM). TNF, IFN-β and IL-1β cytokine expression was measured by ELISA and NF-κB activity by luciferase reporter assay. We found SFN is a potent inhibitor of NF-κB activity and inhibits release of the pro-inflammatory cytokine IL-1β through inhibition of NLRP3 inflammasome activation. Finally, co-incubation of SFN with the glucocorticoid dexamethasone significantly suppressed TNF and IFN-β expression, demonstrating steroid sparing activity of SFN in vitro. Thus, SFN may be a suitable treatment for disruption of inflammatory pathways and suggest some of these effects may be mediated through direct interactions with MIF.

Despite its low prevalence, the potential diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) should be at the forefront of a paediatric cardiologists mind in children with syncope during exercise or emotions. Over the years, the number of children with a genetic diagnosis of CPVT due to a (likely) pathogenic RYR2 variant early in life and prior to the onset of symptoms has increased due to cascade screening programmes. Limited guidance for this group of patients is currently available. Therefore, we aimed to summarise currently available literature for asymptomatic patients with a (likely) pathogenic RYR2 variant, particularly the history of CPVT and its genetic architecture, the currently available diagnostic tests and their limitations, and the development of a CPVT phenotype – both electrocardiographically and symptomatic – of affected family members. Their risk of arrhythmic events is presumably low and a phenotype seems to develop in the first two decades of life. Future research should focus on this group in particular, to better understand the development of a phenotype over time, and therefore, to be able to better guide clinical management – including the frequency of diagnostic tests, the timing of the initiation of drug therapy, and lifestyle recommendations.

This article used text mining processes to map continuity and change in policy principles of the National Disability Insurance Scheme (NDIS) in Australia and reflect on the underlying agendas of reform. Specifically, this research aimed to: (1) examine the substantive content of the NDIS legislative, operational and reform documentation, (2) assess changes in objects, principles and issues over time, and (3) discuss the implications of these shifting logics and agendas. To achieve this, text mining approaches were applied to ten key NDIS documents from 2011 to 2019.

The findings included a low prevalence of ‘rights’-based terminology, sustained attention to Scheme ‘costs’ but limited latterly attention to ‘sustainability’, and increasing prominence of interpersonal (e.g., ‘family’, ‘community’) and decision-making terminology (e.g., ‘decision’, ‘review’). How these shifts have influenced subsequent proposed reforms is explored and ongoing dilemmas about designing policy that ensures rights and entitlements, while balancing cost, sustainability and consistency are identified.

Kelp forests are being degraded and/or lost in many regions, and as such, interest in active kelp restoration approaches to reinstate forests is growing. ‘Green gravel’ is a promising new kelp restoration technique that involves seeding small rocks with kelp zoospores, rearing the gametophyte and juvenile sporophyte stages in aquaria before outplanting them at restoration sites. However, to be considered a viable approach to kelp forest restoration, the efficacy of this technique needs to be assessed across a range of environmental contexts and kelp species. Here, we aimed to understand the utility of green gravel as a kelp restoration technique for wave-exposed intertidal shores. Two substrate types – gravel and cobbles – were seeded with Saccharina latissima, reared in the aquarium and outplanted at two sites along the northeast coast of England. Outplanted rocks were monitored for retention, and the density and length of S. latissima. Juvenile sporophytes persisted on both rock types, although declines in density and variations in length were observed over time. Substrate retention was low, with gravel more likely to be removed from restoration sites compared to cobbles, and all outplanted rocks were lost after eight months. While our initial testing of the green gravel restoration technique on wave-exposed shores was not successful, our results provide important insights for developing/refining the technique and a baseline for comparison for future efforts. However, prior to commencing large-scale kelp restoration in wave-exposed areas using green gravel, further testing of the technique and comparisons with other restoration approaches are needed.

Simple extended constant capacitance surface complexation models have been developed to represent the adsorption of polyaromatic dyes (9-aminoacridine, 3,6-diaminoacridine, azure A and safranin O) to kaolinite, and the competitive adsorption of the dyes with Cd. The formulation of the models was based on data from recent publications, including quantitative adsorption measurements over a range of conditions (varying pH and concentration), acid-base titrations and attenuated total reflectance-Fourier transform infrared spectroscopic data. In the models the dye molecules adsorb as aggregates of three or four, forming outer-sphere complexes with sites on the silica face of kaolinite. Both electrostatic and hydrophobic interactions are implicated in the adsorption processes. Despite their simplicity, the models fit a wide range of experimental data, thereby supporting the underlying hypothesis that the flat, hydrophobic, but slightly charged silica faces of kaolinite facilitate the aggregation and adsorption of the flat, aromatic, cationic dye molecules.