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Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

This study investigates the potential of rehearsal interjections to provide opportunities for novice teachers and teacher educators to discuss topics related to teaching the practice of mathematical defining. Through analysis of video recordings of seven elementary novice teachers' rehearsals about geometric definitions, we identified the problems of practice that initiated rehearsal interjections, the topics discussed during rehearsal interjections, and relations between initiating problems of practice and topics discussed. We found that initiating problems of practice focused overwhelmingly on pedagogical issues, with most related to aspects specific to the teaching of mathematical defining. Likewise, discussions during interjections tended to focus on definitional pedagogical topics. Although epistemic topics were mentioned, they were only conveyed implicitly and at times in conflicting manners. Moreover, few opportunities arose for novices to make sense of student thinking about definitions and the mathematics of shape. Our results illustrate ways in which the goal of improving pedagogy, although important, can overshadow learning of other aspects for teaching mathematical practice.

Training key stakeholders in the design of reasonable adjustments for students with disabilities could promote collaboration and inclusion. We tested the feasibility of a randomized controlled trial to evaluate the effectiveness of online education (intervention) in designing reasonable adjustments by Victorian (Australian) parents and professionals (n = 31). Participants suggested reasonable adjustments for contrived students with varied needs to support their participation in described classroom activities. Data collected pre- and post-intervention, and, at follow-up, were rated across five dimensions: Authenticity, Agency, Real Learning, Strengths Based, and Inclusion. Analyses from 15 intervention and 14 control participants (10 parents, 10 teaching staff, and 9 allied health professionals) showed higher scores for Inclusion post-intervention for the intervention group. This difference was maintained at follow-up, generalized to a new contrived student scenario, and mostly attributable to parents. Online education may improve parents' contribution in the design of reasonable adjustments that promote inclusion. A larger study is warranted.

The study aim was to scope research into student outcomes of co-teaching models to promote inclusive school education for students with disability. A systematized search was conducted of studies addressing models of co-teaching involving two teachers and student outcomes published from January 2008 to June 2019. Each study was appraised for quality. Most of 21 studies that met inclusion criteria were conducted in the United States (n = 17). Fourteen studies followed quantitative approaches, six followed qualitative and one included both. Although the benefits of co-teaching for students were demonstrated, it was difficult to determine comparative effectiveness across models, with only one study providing a systematic comparison. There was some evidence of differential effects across factors such as disability type, grade level, and outcome types, but heterogeneity across study aims, participants characteristics, extent to which co-teaching models were described or implemented, and outcomes targeted precluded meaningful comparisons. Limitations were found in study designs, with appraisal scores ranging from 0.6% to 89%. Hence, the research into student outcomes for various models of co-teaching was found to be limited both in number and quality. Findings point to the need for greater attention to what occurs in classrooms to support positive student outcomes of inclusive education through co-teaching.

Dabrafenib plus trametinib is a promising new therapy for patients affected by BRAFV600E-mutant glioma, with high overall response and manageable toxicity. We described a complete and long-lasting response in a case of recurrent anaplastic pleomorphic xanthoastrocytoma CNS WHO-grade 3 BRAFV600E mutated. Due to very poor prognosis, there are a few described cases of high-grade glioma (HGG) patients treated with the combined target therapy as third-line treatment. The emergence of optimized sequencing strategies and targeted agents, including multimodal and systemic therapy with dabrafenib plus trametinib, will continue to broaden personalized therapy in HGG improving patient outcomes.

BackgroundThe use of Non-Pharmaceutical Interventions (NPIs), such as lockdowns, social distancing and school closures, against the COVID-19 epidemic is debated, particularly for the possible negative effects on vulnerable populations, including children and adolescents. This study therefore aimed to quantify the impact of NPIs on the trend of pediatric hospitalizations during 2 years of pandemic compared to the previous 3 years, also considering two pandemic phases according to the type of adopted NPIs.MethodsThis is a multicenter, quasi-experimental before-after study conducted in 12 hospitals of the Emilia-Romagna Region, Northern Italy, with NPI implementation as the intervention event. The 3 years preceding the beginning of NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (up to September 2020) and a subsequent mitigation measures phase with less stringent restrictions. School closure was chosen as delimitation as it particularly concerns young people. Interrupted Time Series (ITS) regression analysis was applied to calculate Hospitalization Rate Ratios (HRR) on the diagnostic categories exhibiting the greatest variation. ITS allows the estimation of changes attributable to an intervention, both in terms of immediate (level change) and sustained (slope change) effects, while accounting for pre-intervention secular trends.ResultsOverall, in the 60 months of the study there were 84,368 cases. Compared to the pre-pandemic years, statistically significant 35 and 19% decreases in hospitalizations were observed during school closure and in the following mitigation measures phase, respectively. The greatest reduction was recorded for “Respiratory Diseases,” whereas the “Mental Disorders” category exhibited a significant increase during mitigation measures. ITS analysis confirms a high reduction of level change during school closure for Respiratory Diseases (HRR 0.19, 95%CI 0.08–0.47) and a similar but smaller significant reduction when mitigation measures were enacted. Level change for Mental Disorders significantly decreased during school closure (HRR 0.50, 95%CI 0.30–0.82) but increased during mitigation measures by 28% (HRR 1.28, 95%CI 0.98–1.69).ConclusionOur findings provide information on the impact of COVID-19 NPIs which may inform public health policies in future health crises, plan effective control and preventative interventions and target resources where needed.

ABSTRACT To meet environmental standards and sustainability policies, diesel-biodiesel-ethanol blends have been investigated as partial replacements for diesel. This study aimed to evaluate the emissions and performance of a diesel engine using a blend of biodiesel and ethanol. Four blends of biodiesel (7, 10, 15, and 20%) and four blends of ethanol (0, 1, 3, and 5%) were used. The power remained stable with the addition of biodiesel but decreased with the addition of ethanol for all blends. The power was reduced from 76 to 74 kW when the ethanol content increased from 0 to 5%. The addition of 1% ethanol increased the maximum torque linearly from 372 to 378 kW. A slight increase in the specific consumption was observed with the use of biodiesel and ethanol in the blend. An increase in the ethanol fraction from 0 to 5% reduced nitrogen oxide emissions, especially at high loads. Ethanol caused a decrease of up to 42% in nitrogen oxide. At high loads, a reduction in carbon monoxide emissions was observed with an increase in the blends of ethanol and biodiesel. Blends of biodiesel and ethanol with concentrations of 20% biodiesel and 5% ethanol are alternatives to diesel in agricultural tractor engines.

Aim: The study aimed to evaluate the shaping characteristics of ProTaper Ultimate (Dentsply Sirona) and BlueShaper (Zarc4Endo) using microcomputed tomographic imaging technology (micro-CT).Methods: Thirty mesial and distal canals of extracted second mandibular molars with similar anatomy were selected and scanned pre- and postoperatively by micro-CT scanning (SkyScan 1172, Bruker micro-CT) with a voxel size of 11 μm and shaped with two different procedures: ProTaper Ultimate (Group 1: n = 15) and BlueShaper (Group 2: n = 15) were used following the manufacturer’s recommendations up to final 30 apical size. Irrigation was ensured in all groups with 5.25% NaOCl and 10% EDTA during instrumentation. Canal transportation, the volume of removed dentin, and area of untreated surface were matched with preoperative values with Bruker CT Analyser (Bruker micro-CT). Data were statistically analyzed using Student’s t-test.Results: No significant differences were observed between Group 1 and Group 2 in terms of canal transportation, volume of removed dentin, and untreated surfaces. A significant difference (p < 0.05) in the amount of untreated surfaces was found between the mesial and distal canals in both groups.Conclusion: Shaping procedures with both ProTaper Ultimate and BlueShaper demonstrated similar canal enlargement volumes and similar canal transportation without evidence of significant preparation errors. Nevertheless, a high amount of untreated surface was reported for both systems, particularly in distal canals.

Background: Sleeve lobectomy with bronchoplasty is a safe surgical technique for the management of lung cancer and endobronchial localization of extrapulmonary cancers. However, anastomotic complications can occur, and treatment strategies are not standardized. Methods: Data from 280 patients subjected to bronchoplasty were retrospectively analyzed, focusing on surgical techniques, anastomotic complications, and their management. Multivariate analysis was performed, and Kaplan–Meier curves were used to determine survival. Results: Ninety percent of 280 surgeries were for lung cancer. Anastomotic complications occurred in 6.42% of patients: late stenosis in 3.92% and broncho-pleural fistula in 1.78%. The median survival was 65.90 months (95% CI = 41.76–90.97), with no difference (p = 0.375) for patients with (51.28 months) or without (71.03 months) anastomotic complications. Mortality at 30 days was higher with anastomotic complications (16.7% vs. 3%, p = 0.014). Multivariable analysis confirmed pathological stage (N+) as a risk factor for anastomotic complications (p = 0.016). Our mortality (3.93%) and morbidity rate (41.78%) corresponded to recent series results. Conclusions: In our experience, surgery is preferred to avoid life-threatening complications in bronchopleural fistulas. Bronchoscopic balloon dilatation is preferred for benign strictures. The nodal stage is related to complications (p = 0.0014), reflecting the aggressiveness of surgery, which requires extended radical lymphadenectomy.

In this study, the effects of H2O and Cl on the grain size and nucleation delay of plagioclase in basaltic magma were investigated using dynamic and equilibrium experiments at 1150 ∘C, 300 MPa, and oxygen fugacity between FMQ − 1.65 and FMQ + 0.05 (fayalite–magnetite–quartz). Each experiment consisted of five samples of basaltic composition (from the Hamn intrusion in Northern Norway) containing varying amounts of H2O (up to 2 wt %) and Cl (up to 1 wt %). The equilibrium experiments were used as a reference frame for the phase assemblage, geochemical composition, and liquidus temperatures and were compared to thermodynamic models using MELTS software. Experimental phase abundances and plagioclase compositions are in good agreement with the predictions of MELTS. The dynamic experiments were initially heated above the liquidus temperature to destroy crystal nuclei and then kept at 1150 ∘C for 100, 250, or 1800 min. These experiments show that as the concentration of H2O in the melt increases, plagioclase nucleation is delayed, plagioclase abundance decreases, but its size increases. Therefore, the addition of H2O seems to favor plagioclase growth at the expense of nucleation. Thermodynamic and kinetic calculations corroborate an increase in the nucleation delay of plagioclase with increasing H2O content dissolved in the melt, suggesting that H2O decreases the undercooling of the silicate melt. The addition of Cl also seems to delay plagioclase nucleation, although this is not supported by kinetic calculations. Increasing the Cl content decreases plagioclase abundance but does not significantly affect its size. The homogeneous pegmatitic pockets of the mafic–ultramafic Hamn intrusion exhibit several petrological and geochemical features, suggesting that H2O and Cl enrichment in the silicate melt was the origin of the pegmatitic texture. The experimental results presented here indicate that H2O, rather than Cl, may have played an important role in the formation of the pegmatitic texture.

Abstract Brain radiation has been medically used to alter the metabolism of cancerous cells and induce their elimination. Rarely, though, brain radiation has been used to interfere with the pathomechanisms of non-cancerous brain disorders, especially neurodegenerative disorders. Data from low-dose radiation (LDR) on swine brains demonstrated reduced levels of phosphorylated-tau (CP13) and amyloid precursor protein (APP) in radiated (RAD) versus sham (SH) animals. Phosphorylated-tau and APP are involved in Alzheimer’s disease (AD) pathogenesis. We determined if the expression levels of hyperphosphorylated-tau, 3R-tau, 4R-tau, synaptic, intraneuronal damage, and DNA damage/oncogenic activation markers were altered in RAD versus SH swine brains. Quantitative analyses demonstrated reduced levels of AT8 and 3R-tau in hippocampus (H) and striatum (Str), increased levels of synaptophysin and PSD-95 in frontal cortex (FCtx), and reduced levels of NF-L in cerebellum (CRB) of RAD versus SH swine. DNA damage and oncogene activation markers levels did not differ between RAD and SH animals, except for histone-H3 (increased in FCtx and CRB, decreased in Str), and p53 (reduced in FCtx, Str, H and CRB). These findings confirm the region-based effects of sLDR on proteins normally expressed in larger mammalian brains and support the potential applicability of LDR to beneficially interfere against neurodegenerative mechanisms.

The present study is significant because it can contribute to developing sustainable energy strategies and expanding knowledge about renewable energies in Ecuador, specifically by modeling two modules: the thermal module (parabolic solar collectors and energy storage tank) and the Organic Rankine Cycle (ORC) module. The objective was to determine a region in Ecuador where the thermal module exhibits the highest efficiency for solar collectors. Subsequently, a detailed analysis of the ORC module was conducted, considering the working fluid, boiling temperature, condensation temperature, pinch point temperature, solar collector area, and the collector area-to-energy storage volume ratio (Ac/V). Finally, an economic analysis was performed based on the Net Present Value (NPV), Internal Rate of Return (IRR), and payback period of implementing this type of system. After conducting all the respective analyses in the thermal module, while considering the yearly average meteorological data of ten years (2012–2022), it was determined that due to its meteorological conditions, ambient temperature (14.7 ℃) and solar beam radiation (184.5 W/m2), the efficiency of the collectors in the Andean region of Ecuador is higher. This efficiency is further enhanced by using Therminol VP-1 as the thermal fluid, as it possesses better thermodynamic properties than the other fluids analyzed. Similarly, the ORC module analysis results determined that cyclohexane is the working fluid for the ORC, thereby leading to a higher ORC efficiency (25%) and overall system efficiency (20%). Finally, the system was optimized to maximize the IRR and minimize the Ac/V of the collector for a nominal power of 92 kW. As a result, the optimal operating conditions of the system include a solar collector area of 1600 m2, an energy storage tank volume of 54 m3, an electricity production of 23757 MW/year, a total system efficiency of 22%, an IRR of 15.65% and a payback period of 9.81 years.

Abstract Cigarette smoking impairs the lung innate immune response making smokers more susceptible to infections and severe symptoms. Dysregulation of cell death is emerging as a key player in chronic inflammatory conditions. We have recently reported that short exposure of human monocyte-derived macrophages (hMDMs) to cigarette smoke extract (CSE) altered the TLR4-dependent response to lipopolysaccharide (LPS). CSE caused inhibition of the MyD88-dependent inflammatory response and activation of TRIF/caspase-8/caspase-1 pathway leading to Gasdermin D (GSDMD) cleavage and increased cell permeability. Herein, we tested the hypothesis that activation of caspase-8 by CSE increased pro-inflammatory cell death of LPS-stimulated macrophages. To this purpose, we measured apoptotic and pyroptotic markers as well as the expression/release of pro-inflammatory mediators in hMDMs exposed to LPS and CSE, alone or in combination, for 6 and 24 h. We show that LPS/CSE-treated hMDMs, but not cells treated with CSE or LPS alone, underwent lytic cell death (LDH release) and displayed apoptotic features (activation of caspase-8 and -3/7, nuclear condensation, and mitochondrial membrane depolarization). Moreover, the negative regulator of caspase-8, coded by CFLAR gene, was downregulated by CSE. Activation of caspase-3 led to Gasdermin E (GSDME) cleavage. Notably, lytic cell death caused the release of the damage-associated molecular patterns (DAMPs) heat shock protein-60 (HSP60) and S100A8/A9. This was accompanied by an impaired inflammatory response resulting in inhibited and delayed release of IL6 and TNF. Of note, increased cleaved caspase-3, higher levels of GSDME and altered expression of cell death-associated genes were found in alveolar macrophages of smoker subjects compared to non-smoking controls. Overall, our findings show that CSE sensitizes human macrophages to cell death by promoting pyroptotic and apoptotic pathways upon encountering LPS. We propose that while the delayed inflammatory response may result in ineffective defenses against infections, the observed cell death associated with DAMP release may contribute to establish chronic inflammation. CS exposure sensitizes human macrophages to pro-inflammatory cell death. Upon exposure to LPS, CS inhibits the TLR4/MyD88 inflammatory response, downregulating the pro-inflammatory genes TNF and IL6 and the anti-apoptotic gene CFLAR, known to counteract caspase-8 activity. CS enhances caspase-8 activation through TLR4/TRIF, with a partial involvement of RIPK1, resulting on the activation of caspase-1/GSDMD axis leading to increased cell permeability and DAMP release through gasdermin pores [19]. At later timepoints caspase-3 becomes strongly activated by caspase-8 triggering apoptotic events which are associated with mitochondrial membrane depolarization, gasdermin E cleavage and secondary necrosis with consequent massive DAMP release.

The rising prevalence of mental illness is straining global mental health systems, particularly affecting older adults who often face deteriorating physical health and decreased autonomy and quality of life. Early detection and targeted rehabilitation are crucial in mitigating these challenges. Mindfulness acceptance and commitment therapy (ACT) holds promise for enhancing motivation and well-being among the elderly, although delivering such psychological interventions is hindered by limited access to services, prompting exploration of remote delivery options like mobile applications. In this paper, we introduce the BrainHeart App (v.1.1.8), a mobile application tailored to improve physical and mental well-being in seniors. The app features a 10-day ACT program and other sections promoting healthy lifestyle. In a pilot study involving twenty participants, individuals engaged in daily mental exercises for 10 days using the app. Clinical evaluations, including assessments of psychological flexibility, overall cognitive profile, mindfulness disposition, cognitive fusion, and heart rate collected with Polar H10, were conducted at baseline (T0) and one month post-intervention (T1). Analysis revealed significant improvements in almost all neuropsychological scores, with high usability reported (system usability scale average score: 82.3 ± 9.31). Additionally, a negative correlation was found between usability and experiential avoidance (r = −0.51; p = 0.026), and a notable difference in heart rate was observed between baseline and post-intervention (F-value = 3.06; p-value = 0.09). These findings suggest that mindfulness-ACT exercises delivered via the BrainHeart App can enhance the well-being of elderly individuals, highlighting the potential of remote interventions in addressing mental health needs in this population.

Over the last two decades, the craft beer industry has significantly developed with the emergence of thousands of microbreweries all over the world. These are mostly small companies that cannot afford the cost of the process monitoring systems that are usually embedded in the machinery used by industrial breweries, but they need to monitor and control the production process in order to guarantee a constant quality of beer. The development of low-cost systems for monitoring the production process would help microbreweries obtain the desired product quality consistency. In this paper, the authors propose a low-cost system for the real-time identification of the different phases of the alcoholic fermentation of beer. The first results prove the ability of the proposed system to monitor the fermentation and to detect anomalies in the process promptly.

Recently, the therapeutic potential of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) has been extensively studied in both human and veterinary medicine. EVs are nano-sized particles containing biological components commonly found in other biological materials. For that reason, EV isolation and characterization are critical to draw precise conclusions during their investigation. Research on EVs within veterinary medicine is still considered in its early phases, yet numerous papers were published in recent years. The conventional adult tissues for deriving MSCs include adipose tissue and bone marrow. Nonetheless, alternative sources such as synovial fluid, endometrium, gingiva, and milk have also been intermittently used. Fetal adnexa are amniotic membrane/fluid, umbilical cord and Wharton’s jelly. Cells derived from fetal adnexa exhibit an intermediate state between embryonic and adult cells, demonstrating higher proliferative and differentiative potential and longer telomeres compared to cells from adult tissues. Summarized here are the principal and recent preclinical and clinical studies performed in domestic animals such as horse, cattle, dog and cat. To minimize the use of antibiotics and address the serious issue of antibiotic resistance as a public health concern, they will undoubtedly also be utilized in the future to treat infections in domestic animals. A number of concerns, including large-scale production with standardization of EV separation and characterization techniques, must be resolved for clinical application.

Polyethylene terephthalate (PET) degradation by enzymatic hydrolysis is significant for addressing plastic pollution and fostering sustainable waste management practices. Identifying thermophilic and thermostable PET hydrolases is particularly crucial for industrial bioprocesses, where elevated temperatures may enhance enzymatic efficiency and process kinetics. In this study, we present the discovery of a novel thermophilic and thermostable PETase enzyme named Sis, obtained through metagenomic sequence-based analysis. Sis exhibits robust activity on nanoPET substrates, demonstrating effectiveness at temperatures up to 70 °C and displaying exceptional thermal stability with a melting temperature (Tm) of 82 °C. Phylogenetically distinct from previously characterised PET hydrolases, Sis represents a valuable addition to the repertoire of enzymes suitable for PET degradation.

Background: The aim was to assess the diagnostic accuracy of DECT in diagnosing Achilles tendon tears, using MRI as the reference for diagnosis. Methods: This feasibility study conducted prospectively at a single center included consecutive patients suffering from ankle pain who underwent DECT and MRI between April 2023 and October 2023. A total of three radiologists, blinded to the patient’s clinical data, assessed the images. Achille Tendon injuries were diagnosed in case of thickened and inflamed tendons or in case of a partial or complete tear. Diagnostic accuracy values of DECT were calculated using a multi-reader approach. Inter-observer agreement was calculated using k statistics. Results: The final study population included 22 patients (mean age 48.5 years). At MRI, Achille’s tendon lesion was present in 12 cases (54.5%) with 2 cases of complete rupture, 8 cases of partial tear (5 with tendon retraction), and 2 cases of tendon thickening. The mean thickness of injured tendons was 10 mm. At DECT, R1 was allowed to correctly classify 20/22 cases (90.9%), R2 19/22 cases (86.4%), and R3 18/22 cases (81.8%). At DECT, the mean thickness of the positively scored tendon was 10 mm for R1, 10.2 mm for R2, and 9.8 mm for R3. A very good agreement was achieved with regard to the evaluation of tears (k = 0.94), thickness (k = 0.96), and inflammatory changes (k = 0.82). Overall agreement was very good (k = 0.88). Conclusions: DECT showed a good diagnostic performance in identifying Achille’s tendon tears, with respect to MRI.

A new methodology to map Italian coastal areas at risk of flooding is presented. This approach relies on detailed projections of the future sea level from a high-resolution, three-dimensional model of the Mediterranean Sea circulation, on the best available digital terrain model of the Italian coasts, and on the most advanced satellite-derived data of ground motion, provided by the European Ground Motion Service of Copernicus. To obtain a reliable understanding of coastal evolution, future sea level projections and estimates of the future vertical ground motion based on the currently available data were combined and spread over the digital terrain model, using a GIS-based approach specifically developed for this work. The coastal plains of Piombino-Follonica and Marina di Campo (Tuscany Region), Alghero-Fertilia (Sardinia), and Rome and Latina-Sabaudia (Lazio Region) were selected as test cases for the new approach. These coastal stretches are important for the ecosystems and the economic activities they host and are relatively stable areas from a geological point of view. Flood maps were constructed for these areas, for the reference periods 2010–2040, 2040–2070, and 2040–2099. Where possible, the new maps were compared with previous results, highlighting differences that are mainly due to the more refined and resolved sea-level projection and to the detailed Copernicus ground motion data. Coastal flooding was simulated by using the “bathtub” approach without considering the morphodynamic processes induced by waves and currents during the inundation process. The inundation zone was represented by the water level raised on a coastal DTM, selecting all vulnerable areas that were below the predicted new water level. Consequent risk was related to the exposed asset.

Pulmonary cancer is often associated with systemic inflammation and poor nutritional status and these two aspects are strongly correlated and related to the scarce infiltration of a tumor by immune cells. We reviewed all English literature reviews from 2000 to 2024 from PubMed, Scopus and Google Scholar, including original articles, review articles, and metanalyses. We excluded non-English language articles and case reports/case series. Generally speaking, nutritional and inflammatory status largely affect medium and long-term prognosis in lung cancer patients. A correct stratification of patients could improve their preoperative general functional nutritional and inflammatory status, minimizing, therefore, possible treatment complications and improving long-term prognosis.

Traumatic brain injury (TBI) is associated with the development of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy (CTE). Current consensus diagnostic criteria define the pathognomonic cortical lesion of CTE neuropathologic change (CTE-NC) as a patchy deposition of hyperphosphorylated tau in neurons, with or without glial tau in thorn-shaped astrocytes, typically towards the depths of sulci and clustered around small blood vessels. Nevertheless, although incorporated into consensus diagnostic criteria, the contribution of the individual cellular components to identification of CTE-NC has not been formally evaluated. To address this, from the Glasgow TBI Archive, cortical tissue blocks were selected from consecutive brain donations from contact sports athletes in which there was known to be either CTE-NC (n = 12) or Alzheimer's disease neuropathologic change  (n = 4). From these tissue blocks, adjacent tissue sections were stained for tau antibodies selected to reveal either solely neuronal pathology (3R tau; GT-38) or mixed neuronal and astroglial pathologies (4R tau; PHF-1). These stained sections were then randomised and independently assessed by a panel of expert neuropathologists, blind to patient clinical history and primary antibody applied to each section, who were asked to record whether CTE-NC was present. Results demonstrate that, in sections stained for either 4R tau or PHF-1, consensus recognition of CTE-NC was high. In contrast, recognition of CTE-NC in sections stained for 3R tau or GT-38 was poor; in the former no better than chance. Our observations demonstrate that the presence of both neuronal and astroglial tau pathologies facilitates detection of CTE-NC, with its detection less consistent when neuronal tau pathology alone is visible. The combination of both glial and neuronal pathologies, therefore, may be required for detection of CTE-NC.

The aim of this scoping review was to explore the extent to which AAC studies have occurred in inclusive versus segregated settings, the role of AAC in inclusive setting studies, and the evidence for AAC supporting inclusive education of students with complex communication needs. A scoping review of studies published from 2000 to 2020 that involved students who used or could benefit from AAC or their peers conducted within schools yielded 167 studies. Relatively few studies (n=28, 17%) were conducted in inclusive settings. Data from these 28 studies were extracted and appraised for quality. AAC was integrated into intervention in 57% of these studies and in 61% improved use of AAC was an outcome variable, but in only six was this the main aim. Eighty-two students who used or could benefit from AAC were participants across studies. Classroom peers participated across 11 studies, including those in which qualitative designs were employed. The strength of evidence for the role of AAC could not be determined because only 12 studies were experimental and addressed varied aims. Nonetheless, these and seven qualitative studies were appraised as being of high quality. Implications of findings are discussed in terms of extending the evidence to demonstrate the role of AAC, and its potential to support academic and social school inclusion of students with complex communication needs, which may not rely on proficient use of AAC.

Contribution: This article shows that peer instruction can be applied synchronously and effectively to a distance learning course, using the learning platform Moodle together with a videoconferencing tool. Background: Due to the COVID-19 pandemic, all global education has been shifted from face-to-face to distance learning. While the debate on the effectiveness of active learning alternatives to the traditional lectures was still going on, the teachers found themselves facing a further difficulty: how to engage the students in a totally online learning process, where personal contact is completely lacking. The authors found the answer in the online application of peer instruction. Intended Outcomes: The use of online peer instruction (OPI) is expected to engage all the students attending the online lectures in an active learning process, improving their understanding of the topics covered at the same time. Application Design: The use of Moodle has made it possible to bring the peer instruction method online. The appropriate setup of Moodle's Choice and Workshop activities was sufficient to manage the whole process from a technical standpoint, with the teacher managing the communication aspect, via the videoconferencing tool used to give the lectures. Findings: The application of OPI engaged all the students in the online lectures and proved to be effective in improving students' understanding of the topics covered.