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Abstract Purpose This study aimed to investigate whether incorporating pre-injury health status, measured by the American Society of Anesthesiologists (ASA) score, improves outcome prediction models for moderate-to-severe traumatic brain injury (msTBI) patients. Methods We conducted a retrospective single-center study of msTBI patients (2005–2021). The primary outcome was 1-year Glasgow Outcome Scale (GOS, dichotomized as GOS1-3 (unfavorable) vs. 4–5 (favorable)), and secondary outcome was 90-day mortality. Logistic regression evaluated the contribution of ASA score to the International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury (IMPACT) core + CT outcome prediction model incorporating age, admission GCS, pupillary reactivity, Marshall CT classification, hypoxia, hypotension, epidural hematoma, and subarachnoid hemorrhage. Results Among the 720 adult patients that were included 51% had an unfavorable GOS at 1 year. The 90-day mortality was 19%. ASA score and TRISS were independently associated with both outcomes (p

Polar bears (Ursus maritimus Phipps, 1774) rely on seals as their primary prey, yet predator–prey spatial relationships are poorly understood. We examined the spatial relationship between Davis Strait polar bears and harp seals (Pagophilus groenlandicus Erxleben, 1777), using satellite telemetry for both species. We analyzed sea ice trends using remote sensing (1979–2021) to examine how their environment may be changing using four sea ice seasons (freeze-up, winter, break-up, and summer). Sea ice cover decreased and summer season lengthened over time. Polar bears (n = 18) tracked in 1991–2001 for 7–12 months had a mean 95% minimum convex polygon (MCP) home range size of 108 146 km2 (standard error of the mean (SE) = 18 252 km2) and a mean 95% kernel density home range size (kernel density estimate (KDE)) of 76 863 km2 (SE = 12 260 km2). Harp seals (n = 22) tracked for 5–8 months in 1993–2005 had a mean 95% MCP of 693 403 km2 (SE = 74 384 km2) and a mean 95% KDE of 395 316 km2 (SE = 48 688 km2). During freeze-up, the core-use areas of both species did not overlap, but the broad-use areas did. During break-up, the broad-use areas overlapped more than the core-use areas. The space use of both species was influenced by the sea ice seasons and these seasons have changed over time.

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.

The use of mobile applications (apps) is popular among parents and teachers due to their cost-effectiveness and ease of implementation, and the number of apps with the specific aim to increase eye contact for children with autism is growing rapidly. However, research is limited to assess the efficiency of the majority of the apps available for educational purposes. This study was conducted to determine whether the addition of video modeling via an app to ongoing classroom instruction could increase eye contact with familiar and unfamiliar people in children with autism spectrum disorder (ASD). An experimental pretest-posttest control group design was applied with a full intervention group, a partial intervention group, and a control group. Forty-four U.S. students diagnosed with ASD, in kindergarten through third grade, engaged with social skill modules using an iPad app called We Are Friends. The frequency and duration of eye contact were measured. A 3-month follow-up test was given to determine maintenance. Results suggest the addition of the app was effective in increasing eye contact in children with ASD with both familiar and unfamiliar individuals.

Principal turnover has become topic of discussion, attracting attention not only in media, but also among scholars. Research indicate that high turnover rate is problematic for several reasons. First, it jeopardises stability of school management, which is crucial for schools, not only to function well but also to develop as organisations. Second, since studies indicate that principals have an important, yet indirect, effect on student learning, it is reasonable to expect high turnover to impact negatively on both student and school performance. The aim of the study was to map out and describe national variations in principal turnover in Sweden and thus provide a basis for practice-oriented research. To determine the level of turnover and the extent to which particular municipalities or types of municipalities are facing substantially higher turnover than others, statistical data from Statistics Sweden (SCB) were used. Results show that the average principal has worked in the same municipality for approximately six years and changed schools less than once. Yet, results differ between different types of municipalities, i.e. metropolitan, urban, rural and sparsely populated areas. The results raise fundamental, yet often, overseen questions, namely: When and for whom is principal turnover a problem?

Objective: Suicide awareness, encompassing knowledge, attitudes, and behaviors related to suicide, plays a critical role in primary suicide prevention, especially among adolescents. However, little is known about how perceived suicide awareness is apparent in peer support networks in this population. This study examined the presence of suicide awareness homophily in adolescent peer support networks. We also explored other patterns of homophily and identified factors associated with the in-degree popularity of adolescents. Methods: We used baseline data from a non-randomized, cluster-controlled trial assessing the effectiveness of a universal suicide prevention intervention in Swiss secondary schools (n = 194). We assessed perceived suicide awareness, support networks (including in-degree popularity, i.e., receiving a high number of nominations as a supportive peer), and other covariates. Data were analyzed using social network analyses. Results: We found evidence of suicide awareness homophily in peer support networks, where adolescents with high suicide awareness were more likely to connect with peers having high suicide awareness (p

Professional learning based on collegial conversations is an issue worldwide. However, there is a need for deeper knowledge about what happens in such conversations. Based on practice theories and theories of knowledge building environments, this article explores collegial conversations among teachers and school leaders. The findings show three conversation practices that can be of importance in professional learning, although not always in terms of knowledge building discourse moves: knowledge building practices, disrupted knowledge building practices and non-knowledge building practices. The latter two include significant relational aspects. The conclusion is that we need to widen the understanding of knowledge building to achieve professional learning.

Background Chronic subdural haematoma is a collection of ‘old blood’ and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting Neurosurgical units in the UK. Participants Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0–3) or an unfavourable (score of 4–6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (−8.2%, 95% confidence interval −13.3% to −3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be –£97.19. Conclusions This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration This trial is registered as ISRCTN80782810. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information. Plain language summary Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an ‘old’ collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma. Scientific summary Background Chronic subdural haematoma (CSDH) is a common neurological disorder predominantly affecting older people, affecting approximately 5000 people aged over 65 years in the UK each year. Its incidence is increasing owing to an ageing population, alongside the growing use of antithrombotic agents. The majority of CSDHs do not cause symptoms and are managed conservatively. In those that do cause symptoms, surgical evacuation remains the mainstay of management, which achieves a good recovery in approximately 80% of patients. The remaining 10–20% of patients may suffer a recurrence, requiring further surgery. Additional and alternative measures to surgery are sought to improve outcomes in this patient group. Inflammation has been implicated in the pathogenesis of CSDHs, which suggests a role for anti-inflammatory medications, such as steroids. Therefore, steroids may serve as a useful adjunct or even alternative to surgery. However, to date, there is a lack of high-quality evidence in the form of a randomised clinical trial or meta-analysis. This trial investigates the clinical effectiveness of a steroid, dexamethasone, in patients with symptomatic CSDH. Objectives Primary objective The primary objective of the trial was to determine the clinical effectiveness of a 2-week course of dexamethasone for adult patients with a symptomatic CSDH, assessed by comparing the rate of favourable outcomes [defined as a Modified Rankin Scale (mRS) score of 0–3] at 6 months after randomisation between the treatment and the control arm. This outcome was reviewed centrally by a clinically trained investigator blinded to treatment allocation. Secondary objectives The secondary objectives were to compare the following outcomes between the treatment and the control arm of the trial: number of CSDH-related surgical interventions undertaken during the index admission number of CSDH-related surgical interventions undertaken during subsequent admissions in the follow-up period Glasgow Coma Scale (GCS) score at discharge from the neurosurgical unit (NSU) and at 6 months Modified Rankin Scale score at discharge from the NSU and at 3 months Barthel Index score at discharge from the NSU and at 3 and 6 months mortality (30 days and 6 months) EuroQol-5 Dimensions, five-level version (EQ-5D-5L), utility index at discharge from the NSU and at 3 and 6 months length of stay in the NSU discharge destination from the NSU length of stay in secondary care rates of adverse events (AEs). An economic evaluation was also undertaken to estimate the cost-effectiveness of dexamethasone compared with placebo. Tertiary objectives Postoperative recurrence is a tertiary outcome measure and is defined as a symptomatic recurrence requiring reoperation of a previously evacuated ipsilateral CSDH. Methods Trial design The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) trial is a multicentre, pragmatic, clinical phase III, randomised, double-blind, placebo-controlled trial of a tapering 2-week course of dexamethasone in patients with a symptomatic CSDH. The pragmatic design meant that the trial ran in parallel with standard clinical care, with the only difference being the addition of the trial drug (dexamethasone) or placebo. Intervention Two-week tapering course of dexamethasone (with matching placebo as the control). Participants Participants were screened for eligibility from 23 NSUs across the UK, with the admitting neurosurgical team determining eligibility for participation. Participants were adult patients aged ≥ 18 years with a symptomatic CSDH confirmed on cranial imaging (computerised tomography or magnetic resonance imaging of the brain). The patient or their legal representative had to provide informed consent. In the absence of a legal representative, an independent healthcare professional provided authorisation for enrolment. Patients were excluded in the presence of any of the following criteria: presence of a condition for which steroids are clearly contraindicated patients who are (or within 1 month of) receiving regular oral or intravenous glucocorticoid steroids (this did not include inhaled or topical steroids, nor did it include those receiving a single intraoperative dose of dexamethasone for anti-emesis) previous enrolment in this trial for a prior episode time interval from time of admission to the NSU to first dose of trial medication exceeded 72 hours chronic subdural haematoma in the presence of a cerebrospinal fluid shunt severe lactose intolerance or a known hypersensitivity to dexamethasone or other excipients a history of psychotic disorders unwillingness to take products containing gelatine. Patients who were screened but not included in the study were recorded on a screening log and reported centrally, with both the number of failures and the reasons for failure to recruit to the trial documented. Trial procedures Patients were managed in NSUs in accordance with standard practice. In the UK, this typically includes burr hole evacuation with the use of a subdural drain for most symptomatic patients. The decision for surgery or active monitoring was made on an individual patient basis by the blinded admitting clinical team in conjunction with the patient, in keeping with the pragmatic nature of the trial. Enrolment in the trial took place irrespective of the decision to operate and the timing of surgical intervention. Patients were randomised in 1 : 1 allocation using a computer-generated randomisation schedule, stratified by site using permuted blocks of random sizes (two or four). An interactive web-based response system was used to allocate treatment packs of 62 overencapsulated 2-mg dexamethasone tablets or 62 identical placebo capsules. The enrolled participants, clinical and research team and outcome assessors were blinded to the treatment allocation. The assigned treatment was administered as part of the routine drug round by the ward nurses. Oral administration was the preferred option, but administration via a nasogastric tube was offered to those unable to swallow. The latter method required opening of the capsules for crushing of the contents, allowing potential unblinding of the ward nurse. Therefore, the content of any opened capsules was not documented in the patient notes to maintain the blinding of the neurosurgeons and research staff. Trial drug compliance was recorded through inpatient drug charts during admission or by completion of a medication diary. Data were collected at baseline (on admission to the neurosurgical department) as part of routine standard of care, on discharge from the acute NSU, at 30 days, at 3 months and at 6 months. Patients were monitored in line with routine clinical practice until discharge, and at 3 and 6 months, to score clinical outcomes. Sample size This sample size was calculated with the following assumptions: a favourable outcome rate of 80–85% in the control arm and allowing for up to 15% loss to follow-up. A target sample size of 750 patients was needed to detect an increase in favourable outcome rate from 80–85% to 88–93%, with a power of 81–92% at the 5% significance level (two sided). An 8% increase in the rate of favourable outcome (mRS score of 0–3) at 6 months represents a clinically important treatment effect. Statistical analysis Data were analysed in accordance with the prespecified statistical analysis plan that was agreed prior to unblinding of data. Outcome data were analysed using a modified intention-to-treat analysis (all patients were included as randomised, except for those who withdrew consent for participation in the trial and those lost to follow-up). The primary outcome (mRS score at 6 months) was dichotomised into favourable (0–3) or unfavourable (4–6) outcomes. Primary analysis estimated the absolute difference between the intervention arm and the control arm in the proportions achieving a favourable outcome. A normal approximation was used to produce 95% confidence intervals (CIs) and a two-sided p-value testing the null hypothesis of no difference. Secondary analysis included a logistic regression and proportional odds logistic regression of the original mRS score adjusting for baseline covariates of age and Glasgow Coma Scale (GCS) score. Economic evaluation In the base-case analysis, costs were estimated over the 6-month trial period from an NHS and a Personal Social Services perspective. Outcomes were quality-adjusted life-years (QALYs) derived from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), at NSU discharge and at the 3- and 6-month follow-ups. Analyses were undertaken to estimate the mean incremental cost and effect, and enable the net monetary benefit (NMB) (a negative score indicates that the intervention is not estimated to be cost-effective) to be calculated, along with the cost-effectiveness acceptability curve (CEAC) (probability that dexamethasone was cost-effective). NMB and CEAC values at a willingness-to-pay threshold of £20,000 per QALY are reported. Results Primary outcome An outcome of mRS score of 0–3 occurred in 286 out of 341 patients (83.9%) in the dexamethasone arm and 306 out of 339 patients (90.3%) in the placebo arm at 6 months (difference −6.4%, 95% CI −11.4% to −1.4%; p = 0.01). After adjustment for prespecified covariates (age > 70 years and GCS score on admission), the odds ratio (OR) of a favourable outcome with dexamethasone was 0.55 (95% CI 0.33 to 0.91; p = 0.022), favouring placebo. Secondary outcomes Modified Rankin Scale at discharge and 3 months At 3 months, 268 out of 322 patients (83.2%) in the dexamethasone arm and 298 out of 326 patients (91.4%) in the placebo arm had a favourable outcome, for a between-group difference of −8.2% (95% CI −13.3% to −3.1%) in favour of the placebo arm. There was no significant difference in mRS score between the two arms at discharge [255/318 (80.2%) in the dexamethasone arm and 263/316 (83.2%) in the placebo arm for a difference of −3.0% (95% CI −9.1% to 3.0%)]. Mortality At discharge, 8 out of 375 patients (2.1%) in the dexamethasone arm and 2 out of 373 patients (0.5%) in the placebo arm had died (OR 4.08, 95% CI 1.01 to 27.2). At 6 months, 30 out of 341 patients (8.8%) in the dexamethasone arm and 17 out of 339 patients (5.0%) in the placebo arm had died (OR 1.83, 95% CI 0.99 to 3.45). Number of chronic subdural haematoma-related surgical interventions undertaken The number of surgical interventions undertaken during the index admission or during subsequent admissions during the follow-up period was similar in both arms. However, in the subset of patients who received surgery, repeat surgery for recurrence of the CSDH was performed in 6 out of 349 patients (1.7%) in the dexamethasone arm and in 25 out of 350 patients (7.1%) in the placebo arm. EuroQol-5 Dimensions, five-level version, utility index (at discharge and at 3 and 6 months) The mean EQ-5D-5L, utility index scores were compared. At discharge, the difference was −0.03 (95% CI −0.07 to 0.01), favouring placebo. At 3 months, the difference was −0.07 (95% CI −0.12 to −0.02), favouring placebo. At 6 months, the difference was −0.03 (95% CI −0.09 to 0.02), favouring placebo. Glasgow Coma Scale (at discharge and at 6 months) Glasgow Coma Scale was grouped into scores of 9–12 and 13–15. The percentage of patients with a score of 13–15 was similar at discharge (99.7% in the placebo arm vs. 99.2% in the dexamethasone arm). Insufficient data at 6 months prevented analysis. Barthel Index (at discharge and at 3 and 6 months) No significant difference was seen between the placebo arm and the dexamethasone arm at discharge, 3 months or 6 months. Length of stay in the neurosurgical unit The mean length of stay was 9.03 days in the placebo arm and 9.32 days in the dexamethasone arm. Length of stay in secondary care The mean length of stay was 13.0 days in the dexamethasone arm and 13.7 days in the placebo arm, with no significant difference between the two arms (0.95, 95% CI 0.835 to 1.09; p = 0.467). Discharge destination from the neurosurgical unit No significant difference was observed between the placebo arm and the dexamethasone arm when comparing discharge destinations. Rates of adverse events The odds of an adverse event of special interest were greater in the dexamethasone arm than in the placebo arm (OR 3.40, 95% CI 1.81 to 6.85). Similarly, the odds of a serious adverse event occurring were greater in the dexamethasone arm than in the placebo arm (OR 2.49, 95% CI 1.54 to 4.15). Economic evaluation The mean incremental cost for dexamethasone was estimated to be −£143.73 (95% CI −£1793 to £1505), with a QALY of −0.012 (95% CI −0.027 to 0.003), compared with placebo. The associated NMB of dexamethasone compared with placebo was −£97.19, with an estimated 46% probability of being cost-effective. Conclusions Implications for healthcare Dexamethasone for the treatment of symptomatic CSDH resulted in a lower proportion of favourable outcomes, as measured with the mRS, and a larger number of AEs than placebo. This treatment regime was also not estimated to be cost-effective (based on the NMB). Therefore, dexamethasone is not recommended in the treatment of CSDH. Implications for research The results of our literature review indicate that this study is the first multicentre randomised controlled trial to investigate the clinical effectiveness and cost-effectiveness of dexamethasone in the management of symptomatic CSDH. It provides evidence to inform the role of dexamethasone in this condition. Trial registration This trial is registered as ISRCTN80782810. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Patients with SCN8A epileptic encephalopathy exhibit a range of clinical features, including multiple seizure types, movement disorders, and behavioral abnormalities, such as developmental delay, mild-to-severe intellectual disability, and autism. Recently, the de novo heterozygous SCN8A R1620L mutation was identified in an individual with autism, intellectual disability, and behavioral seizures without accompanying electrographic seizure activity. To date, the effects of SCN8A mutations that are primarily associated with behavioral abnormalities have not been studied in a mouse model. To better understand the phenotypic and functional consequences of the R1620L mutation, we used CRISPR/Cas9 technology to generate mice expressing the corresponding SCN8A amino acid substitution. Homozygous mutants exhibit tremors and a maximum lifespan of 22 days, while heterozygous mutants (RL/+) exhibit autistic-like behaviors, such as hyperactivity and learning and social deficits, increased seizure susceptibility, and spontaneous seizures. Current clamp analyses revealed a reduced threshold for firing action potentials in heterozygous CA3 pyramidal neurons and reduced firing frequency, suggesting that the R1620L mutation has both gain- and loss-of-function effects. In vivo calcium imaging using miniscopes in freely moving RL/+ mutants showed hyperexcitability of cortical excitatory neurons that is likely to increase seizure susceptibility. Finally, we found that oxcarbazepine and Huperzine A, a sodium channel blocker and reversible acetylcholinesterase inhibitor, respectively, were capable of conferring robust protection against induced seizures in RL/+ mutants. This mouse line will provide the opportunity to better understand the range of clinical phenotypes associated with SCN8A mutations and to develop new therapeutic approaches.