Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.

Background: Traumatic brain injury (TBI) patients exhibit variable post-injury recovery trajectories. Days at Home (DAH) is a patient-centered measure that captures healthcare transitions and offers a more nuanced understanding of recovery. Here, we use DAH to characterize longterm recovery trajectories for moderate to severe TBI (msTBI) survivors. Methods: This multicenter retrospective cohort study utilized population health data from Ontario to identify adults sustaining isolated msTBI hospitalized between 2009-2021. DAH were calculated in distinct 30-day intervals from index admission to 3 years post-injury; latent class mixed modeling identified unique recovery trajectories and trajectory attributes were quantified. Results: There were 2,510 patients eligible for latent class analysis. Four DAH trajectories were identified: early recovery (69.9%), intermediate recovery (11.4%), late recovery (2.9%), and poor recovery (15.8%). Patients in the poor recovery group were older, more frail, and had lower admission GCS scores, while those in early recovery exhibited lower acute care needs. Intermediate and late recovery groups exhibited protracted transitions home, with near-complete reintegration by 24 months. A prediction model distinguished unfavorable trajectories with good accuracy (C-index=0.824). Conclusions: Despite high initial institutional care requirements, 85% of patients reintegrated into the community within three years of msTBI. These findings shed light on post-injury care requirements for brain-injured patients.

Here, we explore variation in a new record of archaeological house-floor sizes from the southwestern United States relative to spatially explicit time series estimates of local precipitation. Our results show that inequality becomes more severe during periods of high precipitation. This supports the theory suggesting that inequality may emerge where resources are dense, predictable, and clumped within heterogenous and circumscribed environments. Our findings indicate that wealth inequality may emerge among populations with similar subsistence adaptations as a result of local socioenvironmental variation.

Despite the increased awareness and action towards Equality, Diversity and Inclusion (EDI), the glaciological community still experiences and perpetuates examples of exclusionary and discriminatory behavior. We here discuss the challenges and visions from a group predominantly composed of early-career researchers from the 2023 edition of the Karthaus Summer School on Ice Sheets and Glaciers in the Climate System. This paper presents the results of an EDI-focused workshop that the 36 students and 12 lecturers who attended the summer school actively participated in. We identify common threads from participant responses and distill them into collective visions for the future of the glaciological research community, built on actionable steps toward change. In this paper, we address the following questions that guided the workshop: What do we see as current EDI challenges in the glaciology research community and which improvements would we like to see in the next fifty years? Contributions have been sorted into three main challenges we want and need to face: making glaciology (1) more accessible, (2) more equitable and (3) more responsible.

Basal bark application involves applying an oil-soluble herbicide in an oil carrier to the lower 0 to 45 cm of woody stems. For triclopyr, basal bark application typically requires the butoxyethyl ester formulation; however, this cannot be applied when standing water is present, which is common in seasonally flooded wetlands. Recently, the intermediate oil and water-soluble triclopyr acid formulation was registered for use in aquatic sites, allowing for basal bark applications in wetlands where standing water is present. Recent studies indicated that flooding after basal bark treatment can result in triclopyr release to surface waters and subsequent non-target injury. Elevated band application height (i.e., treating a higher band on each stem) may reduce non-target injury potential; however, this modified application technique has not been well tested on woody invasive species. To evaluate this approach, a field study on Brazilian peppertree (Schinus terebinthifolia Raddi) was conducted near Melbourne and Wimauma, FL, on well-established and juvenile rootstocks. Treatments included triclopyr acid at 17, 34, and 69 g L−1 applied in an oil carrier and treatment band heights of 0 to 45 cm and 61 to 107 cm from the groundline. At Melbourne, both band heights treated with 34 or 69 g L−1 resulted in 75% to 100% mortality of mature rootstocks. However, triclopyr applied at 17 g L−1 to the low and elevated band heights resulted in 70% and 11% mortality, respectively. All treatments resulted in 90% to 100% mortality at Wimauma, where the rootstocks were juvenile and much smaller. These findings indicate elevated band heights may be a useful approach for woody plant control and may support an effective management strategy in inundated wetlands that provides better prevention of non-target injury.

The current food system is not only unsustainable but also increasingly inequitable, resulting in food insecurity for many people in the United Kingdom and globally(1). The health impacts of the current food system on disadvantaged communities warrants examination to improve ecological public health nutrition strategies(2). Community gardens and kitchens are frequently established by volunteers in the hope that they will serve as alternatives to the current food environment, building healthy food capacity in the community as well as outdoor physical and social activities for urban residents(3). This remains to be explored in deprived communities in Dorset, UK.

This pilot research was conducted in fourteen adults living in disadvantaged areas in Dorset (Hamworthy-Poole). Inclusion criteria were individuals over 18 years old living in low-income households, who were users of community food garden and kitchen initiatives. The individuals usually attend with their family members in the food growing and cooking activities, including young children and older adults in the programmes. Three semi-structured interviews and three focus groups (total n = 14) were undertaken to uncover views on the importance and roles of these community food initiatives in relation to healthy eating and access to locally grown fresh produce. All discussions were digitally recorded, and data were transcribed verbatim. Qualitative data analysis, using Clarke and Braun’s(4)six steps of thematic analysis, was performed via NVivo software.

Four main themes emerged: Tackling food insecurity & sustainability, Utilization of climate friendly & organic Food, Bridging intergenerational gap and Promoting healthy lifestyle. These food initiatives help in addressing food insecurity from the perspective of the participants. The role of community gardens together with cooking sessions can be further recognised as contributors to community development, access to healthy food such as fresh fruits and vegetables and nurturing skills related to nutritious food preparation.

In conclusion, this research provided insights into the perceptions on how we can design a health promotion initiative that is inclusive and sustainable to tackle food insecurity effectively.

This editorial considers the value and nature of academic psychiatry by asking what defines the specialty and psychiatrists as academics. We frame academic psychiatry as a way of thinking that benefits clinical services and discuss how to inspire the next generation of academics.

Why is parenting in adolescence predictive of maladaptive personality in adulthood? This study sets out to investigate environmental and genetic factors underlying the association between parenting and maladaptive personality longitudinally in a large sample of twins. The present study addressed this question via a longitudinal study focused on two cohorts of twins assessed on aspects of perceived parenting (parent- and adolescent-reported) at age 14 years (n =1,094 pairs). Participants were followed to adulthood, and maladaptive personality traits were self-reported using the Personality Inventory for DSM-5 (PID-5) at age 24 or 34 years. We then modeled these data using a bivariate biometric model, decomposing parenting-maladaptive personality associations into additive genetic, shared environmental, and nonshared environmental factors. Numerous domains of adolescent-reported parenting predicted adult maladaptive personality. Further, we found evidence for substantial additive genetic (ra ranging from 0.22 to 0.55) and (to a lesser extent) nonshared environmental factors (re ranging from 0.10 to 0.15) that accounted for the association between perceived parenting reported in adolescence and adult personality. Perceived parenting in adolescence and maladaptive personality in adulthood may be related due to some of the same genetic factors contributing to both phenotypes at different developmental periods.

Background: Despite the utility of administrative health data, there remains a lack of patient-centered outcome measures to meaningfully capture morbidity after traumatic brain injury (TBI). We sought to characterize and validate days at home (DAH) as a feasible measure to assess population-level moderate to severe TBI (msTBI) outcomes and health resource utilization. Methods: We utilized linked health administrative data sources to identify adults with msTBI patients presenting to trauma centers in Ontario injured between 2009-2021. DAH at 180 days reflects the total number of days spent alive and at home excluding the days spent institutionalized in acute care, rehabilitation, inpatient mental health settings or post-acute readmissions. Construct and predictive validity were determined; we additionally estimated minimally important difference (MID) in DAH180days. Results: There were 6340 patients that met inclusion criteria. Median DAH180days were 70 days (interquartile range 0-144). Increased health resource utilization at baseline, older age, increasing cranial injury severity and major extracranial injuries were significantly associated with fewer DAH180days. DAH180days was correlated to DAH counts at 1-3 years. The average MID estimate from anchor-based and distribution-based methods was 18 days. Conclusions: We introduce DAH180days as a feasible and sufficiently responsive patient-centered outcome measure with construct, predictive and face validity in an msTBI population.

Background: Employment and personal income loss after traumatic brain injury (TBI) is a major source of post-injury stress and barrier to societal reintegration for affected patients. We sought to quantify the labor market implications for tax-filing adult TBI survivors. Methods: We performed a matched difference-in-difference analysis using a national retrospective cohort of working adult TBI survivors injured between 2007-2017. Linear and logistic mixed effects regressions were used to estimate the magnitude of personal income loss and proportion of patients displaced from the workforce in the three post-injury years (Y+1 to Y+3). Results: Among 18,050 patients identified with TBI, the adjusted average loss of personal annual income was $-7,635 dollars in Y+1 and $-5,000 in Y+3. An additional -7.8% individuals were newly unemployed compared to the pre-injury baseline. For mild, moderate, and severe TBI subgroups, income loss was $-3354, $-6750, and $-17375 respectively in Y+3; the proportion of newly unemployed individuals in Y+3 was 5.8%, 9.2%, and 20% lower than baseline. We estimated 500 million dollars of incurred labor markets losses related to TBI in Canada. Conclusions: This work represents the first national cohort data quantifying the labor market implications of TBI. These results may be used to inform post-injury care pathways and vocational rehabilitation.

Background: Meningiomas are the most common intracranial tumor with surgery, dural margin treatment, and radiotherapy as cornerstones of therapy. Response to treatment continues to be highly heterogeneous even across tumors of the same grade. Methods: Using a cohort of 2490 meningiomas in addition to 100 cases from the prospective RTOG-0539 phase II clinical trial, we define molecular biomarkers of response across multiple different, recently defined molecular classifications and use propensity score matching to mimic a randomized controlled trial to evaluate the role of extent of resection, dural marginal resection, and adjuvant radiotherapy on clinical outcome. Results: Gross tumor resection led to improved progression-free-survival (PFS) across all molecular groups (MG) and improved overall survival in proliferative meningiomas (HR 0.52, 95%CI 0.30-0.93). Dural margin treatment (Simpson grade 1/2) improved PFS versus complete tumor removal alone (Simpson 3). MG reliably predicted response to radiotherapy, including in the RTOG-0539 cohort. A molecular model developed using clinical trial cases discriminated response to radiotherapy better than standard of care grading in multiple cohorts (ΔAUC 0.12, 95%CI 0.10-0.14). Conclusions: We elucidate biological and molecular classifications of meningioma that influence response to surgery and radiotherapy in addition to introducing a novel molecular-based prediction model of response to radiation to guide treatment decisions.

Background: Meningiomas have significant heterogeneity between patients, making prognostication challenging. For this study, we prospectively validate the prognostic capabilities of a DNA methylation-based predictor and multiomic molecular groups (MG) of meningiomas. Methods: DNA methylation profiles were generated using the Illumina EPICarray. MG were assigned as previously published. Performance of our methylation-based predictor and MG were compared with WHO grade using generalized boosted regression modeling by generating time-dependent receiver operating characteristic (ROC) curves and computing area under the ROC curves (AUCs) along with their 95% confidence interval using bootstrap resampling. Results: 295 meningiomas treated from 2018-2021 were included. Methylation-defined high-risk meningiomas had significantly poorer PFS and OS compared to low-risk cases (p<0.0001). Methylation risk increased with higher WHO grade and MG. Higher methylome risk (HR 4.89, 95%CI 2.02-11.82) and proliferative MG (HR 4.11, 95%CI 1.29-13.06) were associated with significantly worse PFS independent of WHO grade, extent of resection, and adjuvant RT. Both methylome-risk and MG classification predicted 3- and 5-year PFS and OS more accurately than WHO grade alone (ΔAUC=0.10-0.23). 42 cases were prescribed adjuvant RT prospectively although RT did not significantly improve PFS in high-risk cases (p=0.41). Conclusions: Molecular profiling outperforms conventional WHO grading for prognostication in an independent, prospectively collected cohort of meningiomas.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

How knowledge is created, accessed, stored and disseminated has become a major focus of study when assessing the success or failure of industrial clusters. Marshall (1890; 225) initiated this debate when he noted: ‘The mysteries of the trade become no mysteries; but are as it were in the air’. In the edited collection by Wilson, Corker and Lane (2022), emphasis has been placed on the links between knowledge, knowledge flows and how innovation systems evolve and adapt. This paper builds on their work examining how tacit and codified knowledge is created and disseminated across a cluster. Bathelt et al (2004) have demonstrated how successful clusters build effective ‘global pipelines’ to access knowledge generated elsewhere, prompting us to think how a business history analysis can incorporate these concepts and how these processes have worked in practice. The paper analyses two English clusters and the processes involved in the formation of a common body of knowledge, a ‘knowledge-cum-industrial zeitgeist’ which explains the cluster’s performance. Specifically, it proposes a model that links internally-generated knowledge and ‘global pipelines’ that clusters develop to tap into externally-generated knowledge, which through effective feedback into the ‘local buzz’ results in further innovation and strengthens the cluster’s competitive advantage.

Basal bark treatment with triclopyr butoxyethyl ester is used to control woody invasive plants, including Brazilian peppertree (Schinus terebinthifolia Raddi). However, the ester formulation cannot be applied where standing water is present, which includes wetlands where S. terebinthifolia is found. In 2009, a low-volatile acid formulation of triclopyr was labeled for use in aquatic sites, which allows for basal bark applications when standing water is present. This formulation may have utility for controlling woody plants in standing water. However, anecdotal observations of injury to non-target plants following applications during periods of inundation have been reported. To address this, mesocosm studies were conducted to assess non-target injury through triclopyr root exudation or release from the surface of treated stems via flooding. Mesocosms contained S. terebinthifolia as the treated target, while sugarberry (Celtis laevigata Willd.), buttonbush (Cephalanthus occidentalis L.), and red maple (Acer rubrum L.) were included as non-targets. In the first study, the pathway of root exudation for non-target injury following triclopyr (34 g L−1) basal bark application was isolated with activated charcoal placed at the soil surface. In the second study, mesocosms were flooded to assess triclopyr release from the surface of treated stems and subsequent non-target injury. Defoliation of non-target species posttreatment was ≤8%, and triclopyr was detected at ≤5 µg L−1 in mesocosm wells when activated charcoal was present. Posttreatment non-target defoliation up to 92%, coupled with triclopyr concentrations in surface waters and wells as high as 4,637 µg L−1, indicated triclopyr movement as a result of flooding. Additionally, triclopyr non-target injury from soil activity independent of flooding was observed. These findings provide limited evidence of triclopyr root exudation but considerable evidence of triclopyr release during flooding following basal bark treatment and support a cautionary approach to basal bark application when standing water is present.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

By providing fresh insights into the development of Egyptian corporate networks and business groups between the early 1920s and late 1940s, this article extends the geographical ambit of an expanding field of study. Data from contemporaneous sources were analyzed through social network analysis techniques, in the search for an improved understanding of both the nature of and motivations behind networking in Egypt. In conducting this exercise, this article assesses the success with which the state acted to stimulate local entrepreneurship in its search for greater economic independence. By linking the Egyptian case to a wider literature on corporate networks, the article reveals similarities with other cases of how developing economies responded to the challenges of that era.