Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease process that represents a significant health shock for thousands of patients each year. Return to work outcomes and associated factors require evaluation to counsel patients and identify domains on which to focus clinical efforts. Methods: A systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines was performed using MEDLINE, EMBASE and Cochrane databases from inception to February 2024. Proportion of patients returning to work was collected from included studies. Odds ratios were pooled from studies evaluating the association between pre-rupture demographic variables, post-rupture clinical variables and return to work following aSAH. Results: Literature search yielded 3861 studies, of which 40 studies were included in the final analysis for a total of 6888 patients. On average, 55% (SD 17%) of all patients returned to work after an aSAH. Female sex (male sex OR 1.75), high grade aSAH on presentation (OR 0.30), and need for permanent CSF diversion (OR 0.50) are significantly associated with unemployment after aSAH. Conclusions: Female sex, high grade presentation, and permanent CSF diversion are associated with unemployment after aSAH. About half of all patients that experience aSAH return to work.

Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.

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.

Maladaptive daydreaming is a distinct syndrome in which the main symptom is excessive vivid fantasising that causes clinically significant distress and functional impairment in academic, vocational and social domains. Unlike normal daydreaming, maladaptive daydreaming is persistent, compulsive and detrimental to one’s life. It involves detachment from reality in favour of intense emotional engagement with alternative realities and often includes specific features such as psychomotor stereotypies (e.g. pacing in circles, jumping or shaking one’s hands), mouthing dialogues, facial gestures or enacting fantasy events. Comorbidity is common, but existing disorders do not account for the phenomenology of the symptoms. Whereas non-specific therapy is ineffective, targeted treatment seems promising. Thus, we propose that maladaptive daydreaming be considered a formal syndrome in psychiatric taxonomies, positioned within the dissociative disorders category. Maladaptive daydreaming satisfactorily meets criteria for conceptualisation as a psychiatric syndrome, including reliable discrimination from other disorders and solid interrater agreement. It involves significant dissociative aspects, such as disconnection from perception, behaviour and sense of self, and has some commonalities with but is not subsumed under existing dissociative disorders. Formal recognition of maladaptive daydreaming as a dissociative disorder will encourage awareness of a growing problem and spur theoretical, research and clinical developments.

Background: Considering regional and temporal trends, we sought to explore the incidence of primary malignant brain tumours in Newfoundland and Labrador. Methods: We reviewed all primary, malignant brain tumour cases from 2015-2022 confirmed by St. John’s Health Sciences Centre pathology reports. Incidence rates were standardized using the 2011 Canadian standard population. Results: We included 362 cases. The average annual age-standardized incidence rate of primary, malignant brain tumours per 100,000 was 7.0 (95% CI: 6.3-7.7), lower than the national average (7.93; 95% CI: 7.78-8.08). The incidence of glioblastoma (5.1; 95% CI: 4.5-5.7) was significantly higher than the national average (4.05; 95% CI: 3.95-4.16). Temporal trends revealed that oligodendroglioma incidence spiked from 0.5 (95% CI: 0.2-0.7) in 2015-2019 to 1.5 (95% CI: 0.4-2.6) in 2020 before returning to baseline in 2022. Regional trends indicated a lower incidence of malignant tumours in Labrador-Grenfell (5.1; 95% CI: 2.5-7.6), compared to 6.9 (95% CI: 6.2-7.6) averaged elsewhere. Conclusions: Higher rates of glioblastoma in Newfoundland and Labrador could have a genetic or multi-factorial cause. The increased occurrence of oligodendroglioma during the COVID-19 pandemic necessitates broader investigation, potentially linked to delays in patient care during this period. Regional trends could suggest less access to care in rural populations and underestimated incidence.

Background: Brain metastases indicate an advanced tumour stage for many cancers. We sought to investigate the incidence change of tissue-sampled brain metastases and its relation to staging challenges during the COVID-19 pandemic in Newfoundland and Labrador. Methods: We reviewed all brain metastasis cases from 2015-2022 requiring first-time tissue sampling according to pathology reports from the St. John’s Health Sciences Centre. Incidence rates were calculated using yearly population data by regional health authorities and standardized using the 2011 Canadian standard population. Results: We included 173 cases. The average annual age-standardized incidence rate of brain metastases requiring tissue sampling per 100,000 increased from 2.5 (95% CI: 2.0-3.1) pre-COVID-19 to 4.1 (95% CI: 3.3-5.0) post-COVID-19. Brain metastases from lung primaries accounted for 69% of this increase. While incidence declined to near-baseline in the Eastern provincial population by 2022 (3.3; 95% CI: 1.5-5.1), incidence rose into 2022 in the Western population (8.6; 95% CI: 3.9-13.2). Conclusions: These data suggest a delayed presentation of malignancies during the COVID-19 pandemic and underscore the importance of prioritized staging during times of strain on healthcare systems. Regional, temporal trends suggest regions distant from tertiary care centres could face challenges in resolving cases with delayed presentation post-COVID-19.

The amount of Mn2+ adsorbed or removed from solution by birnessite is several times greater than its reported cation exchange capacity. Extractability of the sorbed Mn2+ decreases with aging. It is uncertain whether the sorbed Mn2+ is oxidized on the surface or incorporated into the structure of birnessite. Using X-ray powder diffractometry and transmission electron microscopy, a study was conducted to examine the mineralogical alteration of birnessite after treatment with various concentrations of MnSO4 and solution pH.

The sorbed Mn2+ was not directly oxidized and remained on the birnessite surface. The sorption of Mn2+ was followed by alteration of birnessite with the formation of new Mn minerals. The specific Mn minerals formed were governed by the pH of the reaction, and the rate of the transformation was determined by Mn2+ concentration and pH. Nsutite and ramsdellite were identified at pH 2.4, crypto-melane at pH 4, groutite at pH 6, and manganite at pH 8. Other Mn minerals formed at these and other pH levels could not be identified. As the concentration of Mn in the solution decreased, the time required to form new minerals from the birnessite increased. The newly formed phases were the result of structural conversion since dissolution of birnessite and reprecipitation of new phases were not observed.

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.

Madole & Harden argue that the Mendelian reshuffling of genes and genomes is analogous to randomised controlled trials. We are not convinced by their arguments. First, their recipe for meeting the demands on randomised experiments is inherently inconsistent. Second, disequilibrium across chromosomes conflicts with their assumption of statistical independence. Third, the genome-wide association study (GWAS) method has many pitfalls, including low repeatability.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

Background: 5-Aminolevulinic acid (5-ALA) is a prodrug used to selectively illuminate high-grade glioma (HGG) tissue intra-operatively, shown to nearly double complete resection rates in a 2006 multicentre, phase III clinical trial. Here, we review the history of the 2020 approval of 5-ALA in Canada and present some of the first preliminary results on resection rates, survival analysis, and adverse effects from a single Canadian center. Methods: We enrolled 76 patients (median age 61 years, 42 male) with suspected HGG amenable to surgical resection between June 2020 and January 2023. Gross total resection was defined by the absence of enhancing lesions on postoperative MRI. We compared the survival distributions of confirmed HGG cases with complete vs. incomplete resection using a log-rank test and Kaplan-Meier statistic. Results: 52 patients were confirmed as having a HGG based on a pathological diagnosis. In 32 of these patients (60.3%) a gross total resection was achieved. 82.76% were still alive at 180 and 270 days, and 72.73% at 360 days. 47.8% had a survival of 600 or more days. Conclusions: 5-ALA fluorescence-guided surgery resulted in high complete resection rates, and improved overall survival comparable to the literature with no notable adverse side effects.

Understanding the subsurface is crucial in building a sustainable future, particularly for urban centers. Importantly, the thermal effects that anthropogenic infrastructure, such as buildings, tunnels, and ground heat exchangers, can have on this shared resource need to be well understood to avoid issues, such as overheating the ground, and to identify opportunities, such as extracting and utilizing excess heat. However, obtaining data for the subsurface can be costly, typically requiring the drilling of boreholes. Bayesian statistical methodologies can be used towards overcoming this, by inferring information about the ground by combining field data and numerical modeling, while quantifying associated uncertainties. This work utilizes data obtained in the city of Cardiff, UK, to evaluate the applicability of a Bayesian calibration (using GP surrogates) approach to measured data and associated challenges (previously not tested) and to obtain insights on the subsurface of the area. The importance of the data set size is analyzed, showing that more data are required in realistic (field data), compared to controlled conditions (numerically-generated data), highlighting the importance of identifying data points that contain the most information. Heterogeneity of the ground (i.e., input parameters), which can be particularly prominent in large-scale subsurface domains, is also investigated, showing that the calibration methodology can still yield reasonably accurate results under heterogeneous conditions. Finally, the impact of considering uncertainty in subsurface properties is demonstrated in an existing shallow geothermal system in the area, showing a higher than utilized ground capacity, and the potential for a larger scale system given sufficient demand.

Over the past 20 years, ash trees (Oleaceae) in parts of the western United States of America and Canada have been subject to infestations with the psyllid Psyllopsis discrepans (Flor) (Hemiptera: Psyllidae). Infested trees show a series of symptoms, including pseudogalls, canopy loss, and in many cases, tree death. This is an expensive problem for urban forests, particularly in the context of emerald ash borer (Coleoptera: Buprestidae) and Dutch elm disease (Ophiostomataceae), which also impact the diversity of urban forests. This paper presents results from a study on the efficacy of two tree-injected insecticides, Orthene® (acephate) and TreeAzin® (azadirachtin). Trees were treated with these insecticides, and egg and adult psyllids were counted. In addition, canopy cover and severity of pseudogalling were visually assessed. Orthene reduced canopy loss and severity and amount of pseudogalling compared to what occurred on control trees; however, there were more eggs on Orthene-treated trees, indicating that any potential benefit was offset by higher egg counts after treatment. Due to the rapid decline of the ash trees, TreeAzin could not be successfully injected.

Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science.

We compare two contracts for managing systematic longevity risk in retirement: a collective arrangement that distributes the risk among participants, and a market-provided annuity contract. We evaluate the contracts’ appeal with respect to the retiree's welfare, and the viability of the market solution through the financial reward to the annuity provider's equityholders. We find that individuals prefer to bear the risk under a collective arrangement than to insure it with a life insurers' annuity contract subject to insolvency risk (albeit small). Under realistic capital provision hypotheses, the annuity provider is incapable of adequately compensating its equityholders for bearing systematic longevity risk.