Development and validation of the Forms and Functions of Aggressive Behavior Scale.

Preventing aggression is a global social issue that warrants additional research with up-to-date measures. Aggressive behaviors manifest in several ways, and the proper assessment should capture its multidimensional nature. We developed the Forms and Functions of Aggressive Behavior Scale (FFABS) to capture the field's current multidimensional understanding of aggression, including its forms (physical, verbal, and relational) and functions (proactive and reactive). Across three studies (N = 1388), we validated the factor structure of the FFABS, obtained partial scalar measurement invariance for males and females, and demonstrated consistent patterns with theoretically related stable constructs and with behavioral measures of inhibitory control and aggressive behaviors, establishing convergent and discriminant validity. We discuss the findings, limitations, practical implications, and future research directions.

What is the carbon footprint of academic clinical trials? A study of hotspots in 10 trials.

BACKGROUND: Clinical trials are fundamental to healthcare, however, they also contribute to anthropogenic climate change. Following previous work to develop and test a method and guidance to calculate the carbon footprint of clinical trials, we have now applied the guidance to 10 further UK and international, academically sponsored clinical trials to continue the identification of hotspots and opportunities for lower carbon trial design. METHODS: 10 collaborating clinical trial units (CTUs) self-identified and a trial was selected from their portfolio to represent a variety of designs, health areas and interventions. Trial activity data was collated by trial teams across 10 modules spanning trial setup through to closure, then multiplied by emission factors provided in the guidance to calculate the carbon footprint. Feedback was collected from trial teams on the process, experience and ease of use of the guidance. RESULTS: We footprinted 10 trials: 6 investigational medicinal product trials, 1 nutritional, 1 surgical, 1 health surveillance and one complex intervention trial. Six of these were completed and four ongoing (two in follow-up and two recruiting). The carbon footprint of the 10 trials ranged from 16 to 765 tonnes CO2e. Common hotspots were identified as CTU emissions, trial-specific patient assessments and trial team meetings and travel. Hotspots for specific trial designs were also identified. The time taken to collate activity data and complete carbon calculations ranged from 5 to 60 hours. The draft guidance was updated to include new activities identified from the 10 trials and in response to user feedback. DISCUSSION: There are opportunities to reduce the impact of trials across all modules, particularly trial-specific meetings and travel, patient assessments and laboratory practice. A trial's carbon footprint should be considered at the design stage, but work is required to make this common place.

Pre-hospital transdermal glyceryl trinitrate for transient ischaemic attack: Data from the RIGHT-2 trial.

BACKGROUND AND PURPOSE: Ambulance trials assessing interventions in suspected stroke patients will recruit patients with currently active symptoms that will resolve into transient ischaemic attack (TIA). The safety and efficacy of glyceryl trinitrate (GTN) in the pre-specified subgroup of patients with TIA in the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial 2 (RIGHT-2) was assessed. METHODS: RIGHT-2 was a pre-hospital-initiated multicentre randomized sham-controlled blinded-endpoint trial that randomized patients with presumed ultra-acute stroke within 4 h of symptom onset to transdermal GTN or sham. Final diagnosis was determined by site investigators. The primary outcome was a shift in modified Rankin Scale (mRS) scores at 90 days analysed using ordinal logistic regression reported as adjusted common odds ratio with 95% confidence intervals (CIs). Secondary outcomes included death or dependence (mRS >2). RESULTS: In all, 109 of 1149 (9.5%) patients had a final diagnosis of TIA (GTN 57, sham 52) with mean age 73 (SD 13) years, 19 (17.4%) had pre-morbid mRS >2, and onset to randomization was 80 min (interquartile range 49, 105). GTN lowered blood pressure by 7.4/5.2 mmHg compared with sham by hospital arrival. At day 90, GTN had no effect on shift in mRS scores (common odds ratio for increased dependence 1.47, 95% CI 0.70-3.11) but was associated with increased death or dependence (mRS >2): GTN 29 (51.8%) versus sham 23 (46.9%), odds ratio 3.86 (95% CI 1.09-13.59). CONCLUSIONS: Pre-hospital ultra-acute transdermal GTN did not improve overall functional outcome in patients with investigator-diagnosed TIA compared with sham treatment.

Predictive accuracy of clinicians estimates of death and recovery after acute intracerebral hemorrhage: pre-specified analysis in INTERACT3 study.

INTRODUCTION: Accurately predicting a patient's prognosis is an important component of decision-making in intracerebral hemorrhage (ICH). We aimed to determine clinicians' ability to predict survival, functional recovery, and return to premorbid activities in patients with ICH. METHODS: Pre-specified secondary analysis of the third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3), an international, multicenter, stepped-wedge cluster randomized controlled trial. Clinician perspectives on prognosis were collected at hospital admission and Day 7 (or before discharge). Prognosis questions were the likelihood of (i) survival at 48 hours and 6 months, (ii) favorable functional outcome (recovery walking and self-care) and (iii) return to usual activities at 6 months. Clinician predictions were compared with actual outcomes. RESULTS: Most clinician participants were from neurosurgery (75%) with a median of 8 working years (IQR 5-14) of experience. Of the 6305 randomized patients who survived 48 hours, 213 (3.4%) were predicted to die (positive predictive value [PPV] 0.99, 95% confidence interval [CI] 0.99-0.99). Of 5435 patients who survived 6 months, 209 (3.8%) were predicted to die (PPV 0.93, 95% CI 0.92-0.93). Predictions on favorable functional outcome (PPV 0.54, 95% CI 0.52-0.56) and satisfied ability to return to usual activities (PPV 0.50, 95% CI 0.49-0.52) were poor. Prediction accuracy varied by working years and region of practice. CONCLUSIONS: In patients with ICH, clinician estimates of death are very good but conversely they are poor in predicting higher levels of functional recovery and activities.

Adaptive Clinical Trials in Stroke.

Designing a clinical trial to evaluate the efficacy of an intervention is often complicated by uncertainty over aspects of the study population, potential treatment effects, most relevant outcomes, dropouts, and other factors. However, once participants begin to be enrolled and partial trial data become available, this level of uncertainty is reduced. Adaptive clinical trials are designed to take advantage of the accumulating data during the conduct of a trial to make changes according to prespecified decision rules to increase the likelihood of success or statistical efficiency. Common adaptive rules address early stopping for benefit or futility, sample size reestimation, adding or dropping treatment arms or altering randomization ratios, and changing the eligibility criteria to focus on responder patient subgroups. Adaptive clinical trials are gaining popularity for clinical stroke research. We provide an overview of the methods, practical considerations, challenges and limitations, and potential future role of adaptive clinical trials in advancing knowledge and practice in stroke.

Demographic disparities in the incidence and case fatality of subarachnoid haemorrhage: an 18-year nationwide study from New Zealand.

Background: Although the incidence and case-fatality of subarachnoid haemorrhage (SAH) vary within countries, few countries have reported nationwide rates, especially for multi-ethnic populations. We assessed the nationwide incidence and case-fatality of SAH in New Zealand (NZ) and explored variations by sex, district, ethnicity and time. Methods: We used administrative health data from the national hospital discharge and cause-of-death collections to identify hospitalised and fatal non-hospitalised aneurysmal SAHs in NZ between 2001 and 2018. For validation, we compared these administrative data to those of two prospective Auckland Regional Community Stroke Studies. We subsequently estimated the incidence and case-fatality of SAH and calculated adjusted rate ratios (RR) with 95% confidence intervals to assess differences between sub-populations. Findings: Over 78,187,500 cumulative person-years, we identified 5371 SAHs (95% sensitivity and 85% positive predictive values) resulting in an annual age-standardised nationwide incidence of 8.2/100,000. In total, 2452 (46%) patients died within 30 days after SAH. Compared to European/others, Maori had greater incidence (RR = 2.23 (2.08-2.39)) and case-fatality (RR = 1.14 (1.06-1.22)), whereas SAH incidence was also greater in Pacific peoples (RR = 1.40 (1.24-1.59)) but lesser in Asians (RR = 0.79 (0.71-0.89)). By domicile, age-standardised SAH incidence varied between 6.3-11.5/100,000 person-years and case fatality between 40 and 57%. Between 2001 and 2018, the SAH incidence of NZ decreased by 34% and the case fatality by 12%. Interpretation: Since the incidence and case-fatality of SAH varies considerably between regions and ethnic groups, caution is advised when generalising findings from focused geographical locations for public health planning, especially in multi-ethnic populations. Funding: NZ Health Research Council.

Efficacy and Safety of Chinese Herbal Medicine in Patients with Acute Intracerebral Hemorrhage: Protocol for a Randomized Placebo-Controlled Double-Blinded Multicenter Trial.

INTRODUCTION: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. This study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. METHODS: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20-30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day × 28 d, oral) or matching placebo. A sample size of 1,504 patients is estimated to provide 90% power (α 0.05) to detect a ≥20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-5L scale at different time points over 6 months of follow-up. The key safety measure is serious adverse events. CONCLUSION: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH.

Twenty-Four-Hour Post-Thrombolysis NIHSS Score As the Strongest Prognostic Predictor After Acute Ischemic Stroke: ENCHANTED Study.

BACKGROUND: This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS AND RESULTS: ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. CONCLUSIONS: In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. REGISTRATION: URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.

Process Evaluation of an Ambulance-Delivered Early Intensive Blood Pressure-Lowering Stroke Trial: Design, Rationale, and Reflection.

INTRODUCTION: The fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) is a large-scale, multicenter, prospective, randomized, open-label, blinded endpoint assessment trial, initiated in an ambulance in China, aiming at evaluating the effectiveness and safety of prehospital blood pressure (BP) lowering in patients with suspected acute stroke and elevated BP. A prespecified process evaluation is intended to explore the implementation of the trial intervention, provide support to interpret the trial outcomes and put forward suggestions to scale up the intervention in broader settings in the future. METHODS: This process evaluation is a mixed-methods design, and follows the Normalization Process Theory (NPT) and the UK Medical Research Council (UK MRC) guidance. Fidelity, reach, acceptability, appropriateness, adoption, sustainability, and relevant contextual factors and mechanisms affecting the implementation of prehospital early intensive BP-lowering treatment will be analyzed. Semi-structured interviews with ambulance staff, ward and emergency department clinicians, and nurses are undertaken to explore perceptions of the intervention, contextual factors, and potential suggestions for future implementation in practice. Data from observational records, surveys, conventional monitoring data, on-site records, and case report forms will be analyzed to understand background care and context. CONCLUSION: The process evaluation of INTERACT4 will provide insights for the implementation of prehospital early intensive BP-lowering intervention in different health systems and help better explain the trial results for further scale up.

Acute gastrointestinal symptoms associated with oil spill exposures among U.S. coast guard responders to the Deepwater Horizon oil spill.

PURPOSE: Research investigating gastrointestinal (GI) symptoms from oil spill-related exposures is sparse. We evaluated prevalent GI symptoms among U.S. Coast Guard responders deployed to the Deepwater Horizon oil spill cleanup. METHODS: Crude oil (via skin contact, inhalation, or ingestion routes), combined crude oil/oil dispersant exposures, other deployment exposures, deployment characteristics, demographics, and acute GI symptoms during deployment (i.e., nausea/vomiting, diarrhea, stomach pain, and constipation) were ascertained cross-sectionally via a post-deployment survey (median time between deployment end and survey completion 185 days) (N = 4885). Log-binomial regression analyses were employed to calculate prevalence ratios (PRs) and 95 % confidence intervals (CI). Effect modification was evaluated. RESULTS: In adjusted models, responders in the highest (versus lowest) tertile of self-reported degree of skin contact to crude oil were more than twice as likely to report nausea/vomiting (PR=2.45; 95 %CI, 1.85-3.23), diarrhea (PR=2.40; 95 %CI, 2.00-2.88), stomach pain (PR=2.51; 95 %CI, 2.01-3.12), and constipation (PR=2.21; 95 %CI, 1.70-2.89). Tests for trend were statistically significant (p < 0.05). Results were similar for crude oil exposure via inhalation and ingestion. Higher PRs for all symptoms were found with combined crude oil/dispersant exposure than with crude oil exposure alone. CONCLUSIONS: These results indicate positive associations between self-reported crude oil and combined crude oil/oil dispersant exposures and acute GI symptoms.

Protocol for a randomized controlled trial of intensive blood pressure control on cardiovascular risk reduction in patients with atrial fibrillation: Rationale and design of the CRAFT trial.

BACKGROUND: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. METHODS: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study. CONCLUSIONS: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT04347330).

Randomised controlled decentralised feasibility trial of a fixed low-dose combination antihypertensive drug strategy to attenuate cognitive decline in high-risk adults.

OBJECTIVES: The Action To promote brain HEalth iN Adults study aimed to determine the feasibility and applicability of recruitment using home blood pressure (BP) monitoring, routine blood biochemistry and videoconference measures of cognition, in adults at high risk of dementia. DESIGN: A decentralised double-blind, placebo-controlled, randomised feasibility trial with a four-stage screening process. SETTING: Conducted with participants online in the state of New South Wales, Australia. PARTICIPANTS: Participants were aged 50-70 years with moderately elevated BP (systolic >120 and <160 mm Hg or diastolic >80 and <95 mm Hg) and ≥1 additional enrichment risk factor of monotherapy treatment of hypertension, diabetes mellitus, elevated low-density lipoprotein cholesterol, obesity, current smoking or a first degree relative with dementia, which indicated an elevated risk for future cognitive decline. INTERVENTION: Triple Pill (active antihypertensive treatment of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg) or placebo Triple Pill (blinded study capsules). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was feasibility of the study expressed as the percentage of participants randomised from those who were screened. Secondary outcomes were the applicability of videoconference measures of cognition and the overall trial, tolerability of the Triple Pill, safety outcomes and medication adherence. RESULTS: The proportion (95% CI) of patients randomised to those screened was 5% (2%-10%). The applicability of the trial expressed as percentage of those who completed all remote assessments over the number of randomised participants was 67% (95% CI 05 to 22%). There were no serious adverse events or withdrawals from treatment. All participants adhered to study medication, except for one person who had two capsules left at the end of the study period. CONCLUSIONS: The feasibility of this decentralised trial on BP lowering in patients at high risk for dementia is low. However, the applicability of remote assessments of cognitive function is acceptable. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000121864.

Culture and Awe: Understanding Awe as a Mixed Emotion.

Recent work is establishing awe as an important positive emotion that offers physical and psychological benefits. However, early theorizing suggests that awe's experience is often tinged with fear. How then, do we reconcile emergent positive conceptualizations of awe with its more fearful elements? We suggest that positive conceptualizations of awe may partially reflect modern Western experiences of this emotion, which make up the majority of participant samples when studying awe. To test whether awe contains more fearful qualities outside of Western cultures, we compared participants' experiences of this emotion in China to those in the United States. In a two-week daily diary study (Study 1), Chinese participants reported greater fear than American participants during experiences of awe, but not a comparison positive emotion. In response to a standardized awe induction (Study 2), Chinese participants reported more fear, whereas American participants reported more positive emotions. Physiological changes in autonomic activity differed by culture only for heart rate, but not skin conductance or respiratory sinus arrhythmia. These findings reveal that awe may be experienced as a more fearful, mixed emotion in China than in the United States and suggest that current positive conceptualizations of awe may reflect a disproportionate reliance on modern Western samples. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-024-00243-3.

Statistical analysis plan for the Chinese Herbal medicine in Acute INtracerebral haemorrhage (CHAIN) trial.

INTRODUCTION: The traditional Chinese medicine (TCM) herbal compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) by reducing brain edema, hematoma absorption, and enhancement of the immune system. We outline the statistical analysis plan (SAP) for the Chinese Herbal medicine in Acute INtracerebral haemorrhage (CHAIN) study. DESIGN: CHAIN is a multicenter, prospective, randomized, double-blind, placebo-controlled trial being undertaken at 20-30 hospitals in China. After the completion of eligibility checks, patients are randomly allocated to FYTF-919 (100 mL per day, oral) or matching placebo over 28 days. A sample size of 1504 patients is estimated to provide 90% power (α 0.05) for a 0.06 absolute improvement in the primary outcome of utility-weighted modified Rankin scale scores at 90 days, analyzed by general linear regression. METHODS: The statistical analysis plan was developed by the study statistician, principal investigators, international experts, and the study project manager. The plan provides details for analyzing baseline characteristics, patient management, and outcomes. It includes provisions for covariate adjustments, subgroup analysis, the handling missing data, and in the conduct of sensitivity analyzes. RESULTS: A predefined statistical analysis plan was established for CHAIN, facilitating transparent and verifiable analysis. CONCLUSIONS: The CHAIN statistical analysis plan was prospectively developed with a focus on maintaining high-quality standards of internal validity to minimise potential analysis biases. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05066620).

Sex Differences in Profile and In-Hospital Death for Acute Stroke in Chile: Data From a Nationwide Hospital Registry.

BACKGROUND: Knowledge of local contextual sex differences in the profile and outcome for stroke can improve service delivery. We aimed to determine sex differences in the profile of patients with acute stroke and their associations with in-hospital death in the national hospital database of Chile. METHODS AND RESULTS: We present a retrospective cohort based on the analysis of the 2019 Chilean database of Diagnosis-Related Groups, which represents 70% of the operational expenditure of the public health system. Random-effects multiple logistic regression models were used to determine independent associations of acute stroke (defined by main diagnosis International Classification of Diseases, Tenth Revision [ICD-10] codes) and in-hospital death, and reported with odds ratios (ORs) and 95% CIs. Of 1 048 575 hospital discharges, 15 535 were for patients with acute stroke (7074 [45.5%] in women), and 2438 (15.6%) of them died during hospitalization. Differences by sex in sociodemographic and clinical characteristics were identified for stroke and main subtypes. After fully adjusted model, women with ischemic stroke had lower in-hospital death (OR, 0.79 [95% CI, 0.69-0.91]) compared with men; other independent predictors included age per year increase (OR, 1.03 [95% CI, 1.03-1.04]), chronic kidney disease (OR, 1.47 [95% CI, 1.20-1.80]), atrial fibrillation (OR, 1.50 [95% CI, 1.26-1.80]), and other risk factors. Conversely, for intracerebral hemorrhage, women had a higher in-hospital mortality rate than men (OR, 1.19 [95% CI, 1.02-1.40]); other independent predictors included age per year increase (OR, 1.009 [95% CI, 1.003-1.01]), chronic kidney disease (OR, 1.55 [95% CI, 1.23-1.97]), oral anticoagulant use (OR, 1.88 [95% CI, 1.37-2.58]), and other risk factors. CONCLUSIONS: Sex differences in characteristics and in-hospital death of hospitalized patients exist for acute stroke in Chile. In-hospital death is higher for acute ischemic stroke in men and higher for intracerebral hemorrhage in women. Future research is needed to better identify contributing factors.

Recommendations for Implementing the INTERACT3 Care Bundle for Intracerebral Hemorrhage in Latin America: Results of a Delphi Method.

INTRODUCTION: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves outcomes after acute intracerebral hemorrhage (ICH). We aimed to establish consensus-based recommendations for the broader integration of the care bundle across Latin American countries (LAC). METHODS: A 3-phase Delphi study allowed a panel of 32 healthcare workers from 14 LAC to sequentially rank statements relevant to 7 domains (training, resources/infrastructure, patient education, blood pressure, temperature, glycemic control, and anticoagulation reversal). The pre-defined consensus threshold was 75%. RESULTS: A total of 43 statements reached consensus by the third round, with 12 new statements emerging through rounds. The highest-ranked statements in each domain emphasized critical aspects, but successful implementation requires appropriate resourcing. Key priorities were continuous training of all healthcare workers in ICH management, establishing protocols aligned with available resources, and collaborative interdisciplinary care supported by institutional networks. Statements related to anticoagulation reversal had the highest priority. CONCLUSIONS: Consensus statements are provided to facilitate integration of the INTERACT3 care bundle to reduce disparities in ICH outcomes in LAC.

Spatiotemporal alterations in the brain oscillations of Arctic explorers.

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

Strand-resolved mutagenicity of DNA damage and repair.

DNA base damage is a major source of oncogenic mutations1. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation2. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication3,4, we observe identical fidelity and damage tolerance for both strands. For small alkylation adducts of DNA, our results support a model in which the same translesion polymerase is recruited on-the-fly to both replication strands, starkly contrasting the strand asymmetric tolerance of bulky UV-induced adducts5. The accumulation of multiple distinct mutations at the site of persistent lesions provides the means to quantify the relative efficiency of repair processes genome wide and at single-base resolution. At multiple scales, we show DNA damage-induced mutations are largely shaped by the influence of DNA accessibility on repair efficiency, rather than gradients of DNA damage. Finally, we reveal specific genomic conditions that can actively drive oncogenic mutagenesis by corrupting the fidelity of nucleotide excision repair. These results provide insight into how strand-asymmetric mechanisms underlie the formation, tolerance and repair of DNA damage, thereby shaping cancer genome evolution.

Harnessing cold adaptation for postglacial colonisation: Galactinol synthase expression and raffinose accumulation in a polyploid and its progenitors.

Allotetraploid white clover (Trifolium repens) formed during the last glaciation through hybridisation of two European diploid progenitors from restricted niches: one coastal, the other alpine. Here, we examine which hybridisation-derived molecular events may have underpinned white clover's postglacial niche expansion. We compared the transcriptomic frost responses of white clovers (an inbred line and an alpine-adapted ecotype), extant descendants of its progenitor species and a resynthesised white clover neopolyploid to identify genes that were exclusively frost-induced in the alpine progenitor and its derived subgenomes. From these analyses we identified galactinol synthase, the rate-limiting enzyme in biosynthesis of the cryoprotectant raffinose, and found that the extant descendants of the alpine progenitor as well as the neopolyploid white clover rapidly accumulated significantly more galactinol and raffinose than the coastal progenitor under cold stress. The frost-induced galactinol synthase expression and rapid raffinose accumulation derived from the alpine progenitor likely provided an advantage during early postglacial colonisation for white clover compared to its coastal progenitor.

Contrast Sensitivity, Visual Field, Color Vision, Motion Perception, and Cognitive Impairment: A Systematic Review.

OBJECTIVES: To examine relationships between visual function (ie, contrast sensitivity, visual field, color vision, and motion perception) and cognitive impairment, including any definition of "cognitive impairment," mild cognitive impairment, or dementia. DESIGN: Systematic review and meta-analyses. SETTING AND PARTICIPANTS: Any settings; participants with (cases) or without (controls) cognitive impairment. METHODS: We searched 4 databases (to January 2024) and included published studies that compared visual function between cases and controls. Standardized mean differences (SMD) with 95% CIs were calculated where data were available. Data were sufficient for meta-analyses when cases were people with dementia. The Joanna Briggs Institute checklists were used for quality assessment. RESULTS: Fifty-one studies/69 reports were included. Cross-sectional evidence shows that people with dementia had worse contrast sensitivity function and color vision than controls: measured by contrast sensitivity (log units) on letter charts, SMD -1.22 (95% CI -1.98, -0.47), or at varied spatial frequencies, -0.92 (-1.28, -0.57); and by pseudoisochromatic plates, -1.04 (-1.59, -0.49); color arrangement, -1.30 (-2.31, -0.29); or matching tests, -0.51 (-0.78, -0.24). They also performed more poorly on tests of motion perception, -1.20 (-1.73, -0.67), and visual field: mean deviation, -0.87 (-1.29, -0.46), and pattern standard deviation, -0.69 (-1.24, -0.15). Results were similar when cases were limited to participants with clinically diagnosed Alzheimer disease. Sources of bias included lack of clarity on study populations or settings and definitions of cognitive impairment. The 2 included longitudinal studies with follow-ups of approximately 10 years were of good quality but reported inconsistent results. CONCLUSIONS AND IMPLICATIONS: In the lack of longitudinal data, cross-sectional studies indicate that individuals with cognitive impairment have poorer visual function than those with normal cognition. Additional longitudinal data are needed to understand whether poor visual function precedes cognitive impairment and the most relevant aspects of visual function, dementia pathologies, and domains of cognition.