Background: Identifying white matter abnormalities after acute concussion is challenging due to variable microstructural changes and individual imaging limitations. Combining diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) improves sensitivity to alterations. This study integrates neuroimaging and behavioural assessments to improve detection and characterization of abnormalities for clinical management. Methods: We recruited 12 recently concussed athletes (21 ± 2.1 years, 7 ± 4.6 days post-injury; 9 completed behavioural testing) and 24 controls. All participants underwent DTI and NODDI to assess white matter integrity. Kinematic performance was evaluated using the Kinarm exoskeleton robot’s Reverse Visually Guided Reaching (RVGR) task. Group differences in imaging and kinematic metrics were analyzed using permutation-based and parametric tests, controlling for age and sex. Results: Concussed athletes had elevated fractional anisotropy, reduced mean and radial diffusivity, and lower isotropic volume fraction in affected tracts. However, no group differences emerged in RVGR parameters, indicating intact sensorimotor function despite imaging abnormalities. Conclusions: Our findings reveal that acute concussion leads to measurable microstructural changes without corresponding functional deficits on a cognitive inhibition task. These findings highlight the clinical utility of neuroimaging for early and precise diagnosis, emphasizing its sensitivity over behavioural measures to detect subtle impairment for acute concussion management.

Background: Ischemic stroke increases the number of glial cells, such as astrocytes, and causes neuronal death, disrupting the neuron-to-glia balance, contributing to neurodegeneration. Treatment with NeuroD-adeno-associated virus (NeuroD1-AVV) may enhance neuronal transdifferentiation and improve motor function, but the optimal administration protocol for the drug has yet to be determined. Methods: Non-human primates (NHPs) underwent middle cerebral occlusion surgery. Fourteen days poststroke, subjects received NeuroD1-AVV according to two distinct protocols: Three high doses and three low doses. Neurological deficits and cognitive performance were measured using the NHP stroke scale and coloured glove shift of set task, respectively. Nine months post-stroke, NHPs were euthanized. Brains were harvested and stained for neuronal (NEUN and MAP2) and glial (GFAP, IBA1) markers using immunofluorescence techniques. Results: Our results indicate that both protocols effectively rebalance the neuron-to-glia cell ratio by decreasing GFAP+ cells in the P1 and P2 NHPS ipsilateral hemispheres. No cognitive performance differences were found across groups; however, P2 had better NHPSS outcomes from months 2 to 9. Conclusions: The findings support both injection protocols in restoring histological balance, with P2 being more effective for motor function rehabilitation. Investigations into neuronal functionality and development levels continue.

Background: Stroke therapies remain an area of ongoing research. Gene therapies offer a novel approach to repair tissue damage, particularly NeuroD1-mediated astrocyte-to-neuron conversion, which regenerates functional neurons after ischemic injury. Here, we applied NeuroD1 therapy in a non-human primates (NHPs) stroke model to evaluate its effects on corticospinal tract (CST) recovery and motor performance. Methods: Eight NHPs underwent middle cerebral artery occlusion (MCAO). Fourteen days later, six animals received intracranial NeuroD1 treatment (three high-dose, three low-dose), while two received a control solution. Neurological and functional performance were assessed daily. MRI scans were performed at baseline and at 7, 30, 90, 120, and 240 days post-MCAO, with the bilateral CST reconstructed at each time point. All procedures followed Canadian Council of Animal Care guidelines and were approved by Queen’s University’s Animal Use Subcommittee. Results: We found that NHPs receiving the control solution exhibited poorer motor recovery and minimal CST reconstruction. In contrast, those treated with a low dose of NeuroD1 demonstrated motor and functional recovery along with CST reconstruction. Notably, animals receiving the higher dose showed the most significant overall recovery including a greater CST integrity. Conclusions: NeuroD1 treatment promotes white matter tract restoration and facilitates motor recovery following stroke.

Background: Ischemic stroke often results in long-term motor impairments due to disrupted corticospinal pathways. Transcranial magnetic stimulation (TMS) motor mapping is a non-invasive technique used to assess corticospinal integrity by measuring motor evoked potentials (MEPs). This study investigates whether MEP amplitudes can predict impairment severity and functional performance in chronic stroke. Methods: Four non-human primates (NHPs) with chronic stroke (> six months) following transient right middle cerebral artery occlusion underwent TMS motor mapping using neuronavigation under ketamine anesthesia. Single pulses of TMS (50-70% of maximum stimulator output) were applied to the affected and contralesional primary motor cortices to elicit MEPs and assess cortical excitability. Intramuscular electromyography recorded muscle responses from the biceps, extensor digitorum longus, and abductor pollicis brevis. Neurological dysfunction was evaluated daily for three weeks using the NHP Stroke Scale, NHP Upper Extremity Motor Dysfunction Scale, and the primate Rankin Scale. Results: MEPs were present in NHP1, NHP3, and NHP4 but absent in NHP2. Stronger MEPs correlated with lower impairment severity and better functional performance, while NHP2 exhibited higher impairment and poorer performance. Conclusions: MEP presence and strength can serve as biomarkers of motor recovery potential, highlighting their role in assessing corticospinal integrity and functional outcomes.

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.

While from an instrumental perspective stakeholder relations can promote sustained competitive advantage, normative arguments underscore the importance of morally informed principles, especially when relational strategies have uncertain future outcomes and are prone to imitation. This study investigates how such instrumental and normative views can be complementary based on the case study of Natura, a cosmetics company procuring natural inputs from the Amazon rainforest via supplier relations that are open to multiple parties, including competitors. The research shows that Natura developed and reinforced a morally informed normative core specifying how the company and its managers should act. This resulted in a long-term commitment to the open relational strategy, especially when future outcomes were largely uncertain, which in turn promoted emergent instrumental gains via deepened relational attachments and substantive stakeholder engagement. Importantly, the company’s controlling shareholders strongly influenced the normative core, thus underscoring the importance of identifying key shareholders and their values.

Since the 1950s, the United Nations (UN) has designated days (e.g., World Wetland Day), years (e.g., Year of the Gorilla) and decades (e.g., Decade on Biodiversity) with a commonly stated goal to raise awareness and funding for conservation-oriented initiatives, and these Days, Years and Decades of ‘…’ (hereafter ‘DYDOs’) continue. However, the effectiveness of these initiatives to achieve their stated objectives and to contribute to positive conservation outcomes is unclear. Here we used a binary analysis change model to evaluate the effectiveness of UN conservation-oriented DYDOs observed between 1974 and 2020. We also examined four case studies to understand the different strategies employed to meet specified conservation goals. We found that DYDOs apparently contributed to positive conservation outcomes when they were tied to social media campaigns and/or when they were strategically situated in current events or global discourse. Although the outcomes of DYDOs were varied, those with longer timescales and those that engaged local communities were more likely to be successful. We suggest that DYDO organizers should identify all possible paths of action through the lens of the change model outlined in this paper to strengthen the value and effectiveness of these initiatives in the future. Using this approach could help ensure that resources are used efficiently and effectively, and that initiatives yield positive conservation outcomes that benefit people and nature.

Dietary therapies have revolutionised treatment for irritable bowel syndrome (IBS). However, response rates to the diet with the highest evidence of efficacy (the low FODMAP diet) remain at 50-75%, suggesting other potential drivers of symptom onset. A low food chemical elimination-rechallenge diet targeting bioactive food chemicals (including salicylates, amines, glutamate and other additives), is commonly applied in Australia in patients exhibiting both gastrointestinal and extra-intestinal symptoms. One key food chemical, salicylate, has been shown to elicit symptoms in IBS patients with aspirin-sensitivity(1), and 77% of IBS patients have reported amine-rich foods trigger symptoms(2). However, data supporting the full low chemical diet is scant, and safety concerns exist due to its restrictive nature potentially causing nutritional deficiencies and disordered eating. This cross-sectional survey aimed to evaluate the frequency of co-existing extra-intestinal symptoms, as well as explore patient perceptions and use of the low chemical diet in those with IBS and healthy controls. Participants with IBS (IBS-Severity Scoring System (IBS-SSS) >75), and healthy controls (not meeting Rome IV and IBS-SSS ≤75) were recruited via online advertisement. Validated questionnaires were used to assess gastrointestinal symptoms (IBS-SSS), extraintestinal symptoms (extended PHQ-12), nutrient (Comprehensive Nutritional Assessment Tool) and food additive intake (IBD-Food additive questionnaire). Additional questionnaires assessed use of dietary therapies with specific focus on food chemicals. Data was analysed using independent samples t-test and chi-square test. 204 IBS (Total IBS-SSS, 277 ± 79) and 22 healthy controls (36 ± 28, p<0.01) completed the study. IBS participants were more likely to report extra-intestinal symptoms including headaches (p<0.01), migraines (p = 0.03), fatigue (p<0.01), difficulty sleeping (p = 0.03), rhinitis (p = 0.02), urticaria (p = 0.04) and mood disturbance (p<0.01). IBS participants were more likely to report at least one food chemical as a trigger for gastrointestinal (38% vs 13%, p = 0.03) and/or extra-intestinal (30% vs 9%, p = 0.04) symptoms. In the IBS group, the most common suspected dietary triggers for gastrointestinal symptoms were salicylates (19%) followed by MSG (17%) and artificial colours (14%); while for extra-intestinal symptoms, MSG (15%) was most common, followed by amines (14%), and sulphites (12%). There was no significant difference in consumption of ultra-processed, additive containing foods. Twenty-one (10%) IBS participants were following a low chemical diet, with dietary advice provided by a dietitian (n = 13), general practitioner (n = 6), gastroenterologist (n = 6), naturopath (n = 3), family/friend (n = 4) and/or the diet was self-initiated (n = 7). Fourteen of the 21 (67%) reported following both a low food chemical and low FODMAP diet. Patients with IBS are more likely to report extra-intestinal symptoms compared to healthy controls. Despite limited evidence, a low food chemical diet is utilised to manage both gastrointestinal and extra-intestinal symptoms. Of concern, many respondents following a low food chemical diet reported also following a low FODMAP diet, which may have implications for nutritional adequacy.

A tripartite structure for the genetic origin of Japanese populations states that present-day populations are descended from three main ancestors: (1) the indigenous Jomon hunter–gatherers; (2) a Northeast Asian component that arrived during the agrarian Yayoi period; and (3) a major influx of East Asian ancestry in the imperial Kofun period. However, the genetic heterogeneity observed in different regions of the Japanese archipelago highlights the need to assess the applicability and suitability of this model. Here, we analyse historic genomes from the southern Ryukyu Islands, which have unique cultural and historical backgrounds compared with other parts of Japan. Our analysis supports the tripartite structure as the best fit in this region, with significantly higher estimated proportions of Jomon ancestry than mainland Japanese. Unlike the main islands, where each continental ancestor was directly brought by immigrants from the continent, those who already possessed the tripartite ancestor migrated to the southern Ryukyu Islands and admixed with the prehistoric people around the eleventh century AD, coinciding with the emergence of the Gusuku period. These results reaffirm the tripartite model in the southernmost extremes of the Japanese archipelago and show variability in how the structure emerged in diverse geographic regions.

Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from specialists of congenital cardiac disease. The aim of this review is to provide a classification, from the perspective of these specialists, based on an understanding of normal and abnormal morphogenesis and anatomy, with emphasis placed on the features of clinical and surgical relevance. We contend that the description of the congenitally malformed aortic root is simplified when approached in a fashion that recognizes the normal root to be made up of 3 leaflets, supported by their own sinuses, with the sinuses themselves separated by the interleaflet triangles. The malformed root, usually found in the setting of 3 sinuses, can also be found with 2 sinuses, and very rarely with 4 sinuses. This permits description of trisinuate, bisinuate, and quadrisinuate variants, respectively. This feature then provides the basis for classification of the anatomical and functional number of leaflets present. By offering standardized terms and definitions, we submit that our classification will be suitable for those working in all cardiac specialties, whether pediatric or adult. It is of equal value in the settings of acquired or congenital cardiac disease. Our recommendations will serve to amend and/or add to the existing International Paediatric and Congenital Cardiac Code, along with the Eleventh iteration of the International Classification of Diseases provided by the World Health Organization.

Background: Despite significant advances in the treatment of neurological disorders, many conditions remain palliative. Neurologists are in a unique position as they are integral in providing patient centered care, understanding neurologic disease and illness trajectory, and how disease can affect patients’ sense of self and values. Currently, little is known about neurologists’ perceptions and challenges in care planning and palliative care for their patients. Methods: A qualitative approach was utilized with semi-structured interviews of ten neurologists. Data was analyzed using a constant comparative method (constructivist grounded theory). Results: Participants represented a broad spectrum of neurologist experience and subspecialties. Four theories were identified: (1) care planning and palliative care are high priorities, (2) neurologic diseases uniquely affect patients and require a dynamic, patient-centered care plan, (3) a care gap exists in providing palliative care for neurologic patients with multifactorial barriers, and (4) opportunities to improve care exist with continuing education, collaboration, and health system support. Conclusions: Neurologists have a key role in care planning and palliative care for patients with chronic neurological diseases. Our findings show that there is a gap in the provision of palliative care. Future directions may include exploring educational opportunities and dedicated health systems to improve care management.

Background: Our aim was to develop a National Quality Indicators Set for the Care of Adults Hospitalized for Neurological Problems, to serve as a foundation to build regional or national quality initiatives in Canadian neurology centres. Methods: We used a national eDelphi process to develop a suite of quality indicators and a parallel process of surveys and patient focus groups to identify patient priorities. Canadian content and methodology experts were invited to participate. To be included, >70% of participants had to rate items as critical and <15% had to rate it as not important. Two rounds of surveys and consensus meetings were used identify and rank indicators, followed by national consultation with members of the Canadian Neurological Society. Results: 38 neurologists and methodologists and 56 patients/caregivers participated in this project. An initial list of 91 possible quality indicators was narrowed to 40 indicators across multiple categories of neurological conditions. 21 patient priorities were identified. Conclusions: This quality indicators suite can be used regionally or nationally to drive improvement initiatives for inpatient neurology care. In addition, we identified multiple opportunities for further research where evidence was lacking or patient and provider priorities did not align.

Quantitative phase analysis (QPA) of slags is complex due to the natural richness of phases and variability in sample composition. The number of phases frequently exceeds 10, with certain slag types (EAF, BOF, blends, stainless) having extreme peak overlap, making identification difficult. Another convolution arises from the variable crystallite sizes of phases found in slag, as well as the mixture of crystalline and amorphous components specific to each slag type. Additionally, polymorphs are common because of the complexity of the steelmaking and slag cooling processes, such as the cation-doped calcium aluminum silicate (Ca3Al2O6, C3A, Z = 24) supercell in LMF slag. References for these doped variants may not exist or in many cases are not known in advance, therefore it is incumbent on the analyzer to be aware of such discrepancies and choose the best available reference. All issues can compound to form a highly intricate QPA and have prevented previous methods of QPA from accurately measuring phase components in slag. QPA was performed via the internal standard method using 8 wt% ZnO as the internal standard and JADE Pro's Whole Pattern Fitting analysis. For each phase, five variables (lattice parameters, preferred orientation, scale factor, temperature factor, and crystallite size) must be accounted for during quantitation, with a specific emphasis on not refining crystallite sizes for iron oxides and trace phases as they are inclined to over-broaden and interact with the background to improve the goodness of fit (R/E value). Preliminary investigations show somewhat reliable results with the use of custom file sets created within PDF-4+ specifically targeted toward slag minerals to further regulate and normalize the analysis process. The objective of this research is to provide a standard protocol for collecting data, as well as to update methodologies and databases for QPA, to the slag community for implementation in a conventional laboratory setting. Currently, Whole Pattern Fitting “Modified” Rietveld block refinement coupled with the addition of a ZnO internal standard gives the most accurate QPA results, though further research is needed to improve upon the complex issues found in this study of the QPA of slags.

The surface of the Greenland Ice Sheet is darkening, which accelerates its surface melt. The role of glacier ice algae in reducing surface albedo is widely recognised but not well quantified and the feedbacks between the algae and the weathering crust remain poorly understood. In this letter, we summarise recent advances in the study of the biological darkening of the Greenland Ice Sheet and highlight three key research priorities that are required to better understand and forecast algal-driven melt: (i) identifying the controls on glacier ice algal growth and mortality, (ii) quantifying the spatio-temporal variability in glacier ice algal biomass and processes involved in cell redistribution and (iii) determining the albedo feedbacks between algal biomass and weathering crust characteristics. Addressing these key research priorities will allow us to better understand the supraglacial ice-algal system and to develop an integrated model incorporating the algal and physical controls on ice surface albedo.

Albedo is a key factor in modulating the absorption of solar radiation on ice surfaces. Satellite measurements have shown a general reduction in albedo across the Greenland ice sheet over the past few decades, particularly along the western margin of the ice sheet, a region known as the Dark Zone (albedo < 0.45). Here we chose a combination of Landsat 4–8 and Sentinel 2 imagery to enable us to derive the longest record of albedo variations in the Dark Zone, running from 1984 to 2020. We developed a simple, pragmatic and efficient sensor transformation to provide a long time series of consistent, harmonized satellite imagery. Narrow to broadband conversion algorithms were developed from regression models of harmonized satellite data and in situ albedo from the Program for Monitoring of the Greenland Ice Sheet (PROMICE) automatic weather stations. The albedo derived from the harmonized Landsat and Sentinel 2 data shows that the maximum extent of the Dark Zone expanded rapidly between 2005 and 2007, increasing to ~280% of the average annual maximum extent of 2900 km2 to ~8000 km2 since. The Dark Zone is continuing to darken slowly, with the average annual minimum albedo decreasing at a rate of $\sim \!-0.0006 \pm 0.0004 \, {\rm a}^{-1}$ (p = 0.16, 2001–2020).

We assessed patterns of enteric infections caused by 14 pathogens, in a longitudinal cohort study of sequelae in British Columbia (BC) Canada, 2005–2014. Our population cohort of 5.8 million individuals was followed for an average of 7.5 years/person; during this time, 40 523 individuals experienced 42 308 incident laboratory-confirmed, provincially reported enteric infections (96.4 incident infections per 100 000 person-years). Most individuals (38 882/40 523; 96%) had only one, but 4% had multiple concurrent infections or more than one infection across the study. Among individuals with more than one infection, the pathogens and combinations occurring most frequently per individual matched the pathogens occurring most frequently in the BC population. An additional 298 557 new fee-for-service physician visits and hospitalisations for enteric infections, that did not coincide with a reported enteric infection, also occurred, and some may be potentially unreported enteric infections. Our findings demonstrate that sequelae risk analyses should explore the possible impacts of multiple infections, and that estimating risk for individuals who may have had a potentially unreported enteric infection is warranted.

Racially and ethnically minoritized populations have been historically excluded and underrepresented in research. This paper will describe best practices in multicultural and multilingual awareness-raising strategies used by the Recruitment Innovation Center to increase minoritized enrollment into clinical trials. The Passive Immunity Trial for Our Nation will be used as a primary example to highlight real-world application of these methods to raise awareness, engage community partners, and recruit diverse study participants.

Pigmented microalgae inhabiting snow and ice environments lower the albedo of glacier and ice-sheet surfaces, significantly enhancing surface melt. Our ability to accurately predict their role in glacier and ice-sheet surface mass balance is limited by the current lack of empirical data to constrain their representation in predictive models. Here we present new empirical optical properties for snow and ice algae and incorporate them in a radiative transfer model to investigate their impact on snow and ice surface albedo. We found ice algal cells to be more efficient absorbers than snow algal cells, but their blooms had comparable impact on surface albedo due to the different photic conditions of their habitats. We then used the model to reconstruct the effect of ice algae on bare ice albedo spectra collected at our field site in southern Greenland, where blooms dropped the albedo locally by between 3 and 43%, equivalent to 1–10 L m$^{-2}$ d$^{-1}$ of melted ice. Using the newly parametrized model, future studies could investigate biological albedo reduction and algal quantification from remote hyperspectral and multispectral imagery.