The effect of a home-based, gamified stability skills intervention on 4-5-year-old children's physical and cognitive outcomes: A pilot study.

BACKGROUND: Stability skills (e.g., static/dynamic balance) are a precursor for other movement skill development (e.g., jumping, catching). However, young children consistently demonstrate low stability and movement skill ability. There is therefore a need to develop effective strategies to improve stability skills in early childhood. AIM: To pilot the effect of a home-based gamified stability skills intervention on 4-5-year-old children's physical skills, self-perceptions and cognitions. METHODS: One-hundred-and-eleven 4-5-year-old children participated from three schools. Two schools were allocated into the intervention group (n = 66 children, 33 boys) and one to the control group (n = 45 children, 25 boys). Stability, fundamental movement skills, perceived motor competence, and cognition were assessed at baseline and at post-intervention. The intervention group was given a booklet detailing the 12-week gamified stability skill intervention. The control group participated in their usual weekly activities. RESULTS: A series of ANCOVAs controlling for baseline values demonstrated significantly higher stability skills (F(1,93) = 24.79, p < 0.001, partial η2 = 0.212), fundamental movement skills (F(1,94) = 15.5, p = < 0.001, partial η2 = 0.139), perceived motor competence (F(1,96) = 5.48, p = 0.021, partial η2 = 0.054) and cognition (F(1,96) = 15.5, p = < 0.001, partial η2 = 0.139) at post-test for the intervention versus control groups. DISCUSSION: This study demonstrates that a home-based, gamified, stability skills intervention enhances stability skills, fundamental movement skills, perceived motor competence and cognition in children aged 4-5-years old.

The influence of inhibitors of apoptosis proteins (IAPs) on chronic rhinosinusitis with nasal polyps.

BACKGROUND: Inhibitors of apoptosis proteins (IAPs) modulate the inflammatory process, and may facilitate the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to observe if IAPs were differently expressed between patients with CRSwNP and controls, and to correlate the expression of IAPs with some inflammatory markers, as with the response to nasal corticosteroids in patients with CRSwNP. METHODOLOGY: We obtained nasal biopsies from patients with CRSwNP (n=27) and controls (n=16). qRT-PCR measured the expression of IAPs and caspases, while Luminex assay measured the concentration of cytokines. Unpaired parametric tests and Principal Component Analysis (PCA) were used for statistical analysis. RESULTS: We observed lower expression of IAP genes (XIAP, BIRC2/IAP1, and BIRC3/IAP2) in CRSwNP patients compared to controls, and we identified that patients with bad response to corticosteroids presented lower levels of BIRC2/IAP1, XIAP, BCL2, CASP9, and IL-17, and higher levels of CASP7 and TGF-B. CONCLUSIONS: IAPs expression was downregulated in CRSwNP, and was associated with poorer response to nasal corticosteroids. The present findings suggest the importance of IAPs as a link between environment and the host inflammatory responses, and this pathway could be explored as a potential new target therapy for patients with CRSwNP.

Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

Solar photo-Fenton and persulphate-based processes for landfill leachate treatment: A critical review.

Landfilling is the most usual solid waste management strategy for solid residues disposal. However, it entails several drawbacks such as the generation of landfill leachate that seriously threaten human life and the environment due to their toxicity and carcinogenic character. Among various technologies, solar photo-Fenton and sulphate-based processes have proven to be suitable for the treatment of these polluted streams. This review critically summarises the last three decades of studies in this field. It is found that the solar homogeneous photo-Fenton process should be preferably used as a pre- and post-treatment of biological technologies and as a standalone treatment for young, medium, and mature leachates, respectively. Studies on heterogeneous solar photo-Fenton process are lacking so that this technology may be scaled-up for industrial applications. Sulphate radicals are attractive for removing both COD and ammonia. However, no study has been reported on solar sulphate activation for landfill leachate treatment. This review discusses the main advances and challenges on treating landfill leachate through solar AOPs, it compares solar photo-Fenton and solar persulphate-based treatments, indicates the future research directions and contributes for a better understanding of these technologies towards sustainable treatment of landfill leachate in sunny and not-so-sunny regions.

Multi-Domain Interventions for Dementia Prevention - A Systematic Review.

OBJECTIVES: There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may individually or collectively be undertaken to increase one's odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia. DESIGN, SETTING AND PARTICIPANTS: This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults (≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English. RESULTS: The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone). CONCLUSION: This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions.

Two-Year Prognostic Utility of Plasma p217+tau across the Alzheimer's Continuum.

BACKGROUND: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-ß (Aß) and tau in Alzheimer's Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aß and tau in predicting cognitive decline are unknown. OBJECTIVES: To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aß (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aß (A+) and tau (T+) with and without p217+tau pre-screening. DESIGN: A prospective observational cohort study. SETTING: Participants of the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT). PARTICIPANTS: 153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) individuals. MEASUREMENTS: Baseline p217+tau Simoa® assay, 18F-MK6240 tau-PET and 18F-NAV4694 Aß-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years. RESULTS: In CI, p217+tau was a significant predictor of change in MMSE (ß = -0.55, p < 0.001) and CDR-SB (ß =0.61, p < 0.001) with an effect size similar to Aß Centiloid (MMSE ß = -0.48, p = 0.002; CDR-SB ß = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: ß = -0.62, p < 0.001; CDR-SB: ß = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (ß = -0.22, p = 0.008). Screening pT+ CI participants into a trial could lead to 24% reduction in sample size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26-38% biomarker test cost-saving in the CU. CONCLUSIONS: Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.

Sub-Bandgap Sensitization of Perovskite Semiconductors via Colloidal Quantum Dots Incorporation.

By taking advantage of the outstanding intrinsic optoelectronic properties of perovskite-based photovoltaic materials, together with the strong near-infrared (NIR) absorption and electronic confinement in PbS quantum dots (QDs), sub-bandgap photocurrent generation is possible, opening the way for solar cell efficiencies surpassing the classical limits. The present study shows an effective methodology for the inclusion of high densities of colloidal PbS QDs in a MAPbI3 (methylammonium lead iodide) perovskite matrix as a means to enhance the spectral window of photon absorption of the perovskite host film and allow photocurrent production below its bandgap. The QDs were introduced in the perovskite matrix in different sizes and concentrations to study the formation of quantum-confined levels within the host bandgap and the potential formation of a delocalized intermediate mini-band (IB). Pronounced sub-bandgap (in NIR) absorption was optically confirmed with the introduction of QDs in the perovskite. The consequent photocurrent generation was demonstrated via photoconductivity measurements, which indicated IB establishment in the films. Despite verifying the reduced crystallinity of the MAPbI3 matrix with a higher concentration and size of the embedded QDs, the nanostructured films showed pronounced enhancement (above 10-fold) in NIR absorption and consequent photocurrent generation at photon energies below the perovskite bandgap.

Immune-mediated hematological disease in dogs is associated with alterations of the fecal microbiota: a pilot study.

BACKGROUND: The dog is the most popular companion animal and is a valuable large animal model for several human diseases. Canine immune-mediated hematological diseases, including immune-mediated hemolytic anemia (IMHA) and immune thrombocytopenia (ITP), share many features in common with autoimmune hematological diseases of humans. The gut microbiome has been linked to systemic illness, but few studies have evaluated its association with immune-mediated hematological disease. To address this knowledge gap, 16S rRNA gene sequencing was used to profile the fecal microbiota of dogs with spontaneous IMHA and ITP at presentation and following successful treatment. In total, 21 affected and 13 healthy control dogs were included in the study. RESULTS: IMHA/ITP is associated with remodeling of fecal microbiota, marked by decreased relative abundance of the spirochete Treponema spp., increased relative abundance of the pathobionts Clostridium septicum and Escherichia coli, and increased overall microbial diversity. Logistic regression analysis demonstrated that Treponema spp. were associated with decreased risk of IMHA/ITP (odds ratio [OR] 0.24-0.34), while Ruminococcaceae UCG-009 and Christensenellaceae R-7 group were associated with increased risk of disease (OR = 6.84 [95% CI 2-32.74] and 8.36 [95% CI 1.85-71.88] respectively). CONCLUSIONS: This study demonstrates an association of immune-mediated hematological diseases in dogs with fecal dysbiosis, and points to specific bacterial genera as biomarkers of disease. Microbes identified as positive or negative risk factors for IMHA/ITP represent an area for future research as potential targets for new diagnostic assays and/or therapeutic applications.

Evaluation of a battery of biotests to improve waste ecotoxicity assessment (HP 14), using incineration bottom ash as a case study.

The assessment of waste ecotoxicity (hazardous property HP14 in the European Union) is fundamental for proper waste classification and safe application/disposal. Biotests are relevant for evaluating waste complex matrices, but their efficiency is crucial to encourage their adoption at the industrial level. This work aims at evaluating possibilities of improving the efficiency of a biotest battery previously suggested in the literature, regarding test selection, duration, and/or laboratory resources optimization. Fresh incineration bottom ash (IBA) was the case study. The test battery analysed included standard aquatic (bacteria, microalgae, macrophytes, daphnids, rotifers, fairy shrimp) and terrestrial (bacteria, plants, earthworms, collembolans) organisms. The assessment followed an Extended Limit Test design (three dilutions of eluate or solid IBA) and the Lowest Ineffective Dilution (LID-approach) for ecotoxicity classification. The results emphasize the importance of testing different species. It was also evidenced that tests with daphnids and earthworms may be shortened to 24 h; the miniaturization of tests is suitable as e.g. differential sensitivity of microalgae and macrophytes was captured with low variability; alternative testing kits can be used when methodological difficulties are found. Microalgae were more sensitive than macrophytes. Similar results were found for the Thamnotoxkit and daphnids test for eluates with natural pH, so the former may be used as an alternative. B. rapa was the most sensitive organism, suggesting that it may be tested as the only terrestrial plant species and that minimum test duration is appropriate. F. candida does not appear to add information to the battery. The differences in sensitivity of A. fischeri and E. fetida compared to the remaining species were not significant enough to exclude them from the battery. Thus, this work suggests a biotest battery to test IBA comprising aquatic tests - Aliivibrio fischeri, Raphidocelis subcapitata (miniaturised test), and Daphnia magna (24 h when clear deleterious effects are observed) or Thamnocephalus platyurus (toxkit) - and terrestrial tests - Arthrobacter globiformis, Brassica rapa (14 d), and Eisenia fetida (24 h). Testing waste with natural pH is also recommended. The Extended Limit Test design considering the LID-approach seems useful in waste testing, particularly for the industry, involving low effort, test material requirements, and few laboratory resources. The LID-approach allowed for differentiating ecotoxic from non-ecotoxic effects and captured different sensitivities between species. Ecotoxicological assessment of other waste may benefit from these recommendations, but caution should be taken given the properties of each waste type.

An integrated characterisation of incineration bottom ashes towards sustainable application: Physicochemical, ecotoxicological, and mechanical properties.

Environmental protection is a central concern regarding municipal solid waste incineration bottom ash (IBA) management, but the assessment of waste Hazardous Property HP14 (ecotoxicity) is still under debate. Civil engineering applications may be a suitable management strategy. This work aimed at evaluating IBA regarding mechanical behaviour and environmental hazardous potential, including a biotest battery for ecotoxicity assessment (comprising miniaturised tests), to explore its potential for safe utilization. Physical, chemical, ecotoxicological (Aliivibrio fischeri, Raphidocelis subcapitata, Lemna minor, Daphnia magna, Lepidium sativum), and mechanical (one-dimensional compressibility, shear strength) analyses were performed. The low leaching for potentially toxic metals and ions complied with European Union (EU) limit values for non-hazardous waste landfills. No relevant ecotoxicological effects were found. The biotest battery seems suitable for ecotoxicological assessment in the aquatic ecosystem, providing wide information on waste impact on different trophic/functional levels and chemical uptake routes, simultaneously involving short-duration tests and reduced amounts of waste. IBA presented more compressibility than sand, but its mixture with sand (30%:70%) was closer to sand compressibility. IBA (lower stresses) and the mixture (higher stresses) showed slightly higher shear strength than sand. Overall, IBA presented the potential for valorisation as loose aggregates from an environmental and mechanical viewpoint in a circular economy framework.

A dense ring of the trans-Neptunian object Quaoar outside its Roche limit.

Planetary rings are observed not only around giant planets1, but also around small bodies such as the Centaur Chariklo2 and the dwarf planet Haumea3. Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius4 of 555 km and possesses a roughly 80-km satellite5 (Weywot) that orbits at 24 Quaoar radii6,7. The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar's classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments8, can maintain a ring far away from the body. Moreover, Quaoar's ring orbits close to the 1/3 spin-orbit resonance9 with Quaoar, a property shared by Chariklo's2,10,11 and Haumea's3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies.

Evaluation of the Fiscal Costs and Consequences of Alzheimer's Disease in Germany: Microsimulation of Patients' and Caregivers' Pathways.

BACKGROUND: Alzheimer's disease is a severe condition, impacting individual's wellbeing and independence in daily activities. Informal care provision is common and of great value to societies but is not without negative externalities to households and the broader economy. OBJECTIVES: Estimate the lifetime incremental fiscal consequences of Alzheimer's disease in community-based individuals and their informal caregivers. SETTING: The fiscal consequences of Alzheimer's disease was modeled using the German government and social security perspective. PARTICIPANTS: Synthetic cohort containing 1,000 pairs of people with Alzheimer's disease and their informal caregivers, compared to 1,000 demographically identical pairs from the general population. DESIGN: Disease progression was modeled using published equations and a state-transition microsimulation framework. Labor participation, financial support and paid taxes were estimated according to cognitive decline and caregiving responsibilities using German labor statistics and tax rates. Healthcare costs were sourced from several German publications. Costs and life-years were discounted at 3% annually. MEASUREMENTS: Results are reported as lifetime incremental differences in total tax revenue and transfer payments between the cohort affected by Alzheimer's disease and their general population analogues. RESULTS: The Alzheimer's disease-affected pair was associated with net incremental fiscal losses of €74,288 ($85,037) to the German government and social security over the lifetime of people with Alzheimer's disease. Most costs were lost taxes on employment earnings (48.4%) due to caregivers working reduced hours. Caregivers were estimated to earn €56,967 ($65,209) less than their general population analogues. Financial support for informal and formal care accounted for 20.4%, and medical healthcare costs represented 24.0% of the incremental fiscal losses. Sensitivity analyses confirmed the robustness of the model results. In a cohort with early onset Alzheimer's disease, incremental fiscal losses were predicted to be €118,533 ($114,209) over the lifetime of people with Alzheimer's disease. CONCLUSIONS: Alzheimer's disease externalities profoundly impact public economics for governments and should be considered to inform policy making and healthcare planning.

Development of a low voltage railgun in the context of a swept lightning stroke on an aircraft.

When aircraft are struck by lightning, the aircraft's structural fuselage and components are stressed by electrical and thermo-mechanical constraints, which imposes a need for reliable experimental test benches to design accurate and enhanced lightning protection. In order to reproduce the in-flight conditions of an aircraft in a laboratory, the aim of this work is to design and implement launch equipment able to propel aeronautical test samples at speeds characteristic of an aircraft- from 10 m/s for ultra-light gliders to 100 m/s for airliners-before striking it with an electric arc within the laboratory dimensions of several meters. After a comparison of several propulsion techniques, the selected solution is an augmented electromagnetic railgun launcher. Since it requires the injection of a high current to be efficient and a low voltage operative point for safety considerations, specific and original electric generator and rail structures have been designed and experimentally implemented. Particular attention has been paid to the experimental problems encountered and mainly the sliding contact, since almost no literature references are available for railgun equipment at this level of performance. Then, based on different experimental implementations, a dynamic and ballistic model of the projectile has been developed to evaluate and characterize friction forces with the aim of predicting launcher performances with different inputs. This serves to control the speed of the material test sample during the lightning strike. Finally, the railgun equipment has been coupled to a lightning generator to reproduce the lightning strike of an aircraft respecting in-flight conditions.

Can Specular Gloss Measurements Predict the Effectiveness of Finishing/Polishing Protocols in Dental Polymers? A Systematic Review and Linear Mixed-effects Prediction Model.

PURPOSE: The current gold standard measure to assess polishing efficacy is surface roughness (SR) assessed in laboratory research. Specular gloss (SG) has been negatively correlated to SR, which raises the following question: Can SG be used to accurately determine the effectiveness of a finishing/polishing procedure in direct resin composites? METHODS: A systematic approach and search strategy, following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, was developed and conducted in five electronic databases: PubMed/Medline, Scopus, Web of Science, EMBASE (Ovid), and SciELO/LILACS to identify laboratory studies that assessed SR and SG, simultaneously, of resin composites, without date or language restriction. Risk of bias assessment was carried out by two reviewers, independently. From the extracted quantitative data of SG/SR, regression analyses were performed, and a linear mixed-effects prediction model was derived using the nimble package in R (v4.0.3). RESULTS: A total of 928 potential studies were found, out of which, 13 were eligible after criterion screening. Experimental groups featured 31 resin composites of six different filler types, with the most common being microhybrids followed by nanohybrids. More than half of the studies initially reported a linear correlation between SR and SG, which ranged from r2 = 0.34-0.96. Taking into account the regression analysis and prediction model posteriorly performed, the corresponding SG threshold for 0.2 µm is estimated to be >55 GU. Most of the evidence was classified as moderate or high risk of bias. CONCLUSION: SG is universally correlated to SR in polymers, and a reference value of >55 GU is proposed, above which samples are considered well polished.

Beta-blockers for the treatment of arrhythmias: Bisoprolol - a systematic review.

OBJECTIVES: Beta-blockers have long been successfully used for the treatment of both supraventricular and ventricular arrhythmias. However, differences exist between their chemical structure, pharmacokinetic and pharmacodynamic properties (absorption, bioavailability, metabolism, hydrophilic or lipophilic character, selective or non-selective nature, the presence or absence of intrinsic sympathomimetic activity), which may confer different antiarrhythmic properties to different beta-blockers. The aim of this study was to analyze the current existing evidence for bisoprolol for the treatment of both supraventricular and ventricular arrhythmias. MATERIAL AND METHODS: Using the keywords "bisoprolol" and "arrhythmias" or "atrial fibrillation" or "ventricular tachycardia" or "premature ventricular complexes" or "ventricular fibrillation", the Medline database was searched for articles in English or French until April 2020 assessing the role of bisoprolol in the treatment of arrhythmias. Data was then analyzed according to the type of arrhythmia treated and the quality of evidence using the GRADE approach. RESULTS: A total of 325 studies were identified, of which 28 were considered relevant to the current topic. Among these studies, 19 assessed the role of bisoprolol for the treatment of supraventricular arrhythmias, 8 its role in treating ventricular arrhythmias and 1 its role in supraventricular and ventricular arrhythmias. The quality of evidence varied from low (7 studies) to high (5 studies). CONCLUSION: Current evidence exists supporting the use of bisoprolol for the treatment of supraventricular arrhythmias, especially for rate control during atrial fibrillation. Evidence also exists for its efficacy in the treatment of ventricular arrhythmias, both in primary and in secondary prevention.

Modelling the Pan-European Economic Burden of Alzheimer's Disease.

Background: Recent advances open the opportunity of altering the course of Alzheimer's disease (AD) through lifestyle-based modifications and novel therapies. Ensuring that society is investing limited budgets in the interventions that have the greatest potential to generate tangible impact will require tools to guide policymakers. Objectives: To build on previous studies to develop an economic model that estimates the societal burden of AD and evaluates the potential impact of novel interventions in six large European countries. Design: AD progression was modelled using a published Markov structure with a 40-year time horizon to estimate lifetime costs and life years in a cohort aged 65 years and above diagnosed with mild cognitive impairment due to AD (MCI-AD) in 2020. Demographic projections were utilized to estimate the prevalence of MCI-AD up to 2100, total corresponding costs and life years. The model allows a comparison of costs associated with the introduction of a hypothetical new disease-modifying therapy that slows disease progression between MCI-AD and all AD-Dementia stages as well as a 'delayed onset' scenario where disease progression is halted at the MCI-AD stage, potentially occurring, for example, through lifestyle-based modifications. Results: The 2022 present value of total lifetime costs for this cohort moving through all disease stages is ~€1.2T. Approximately 80% of the present value of lifetime costs in our model are driven by informal care and non-medical direct costs. Our model suggests that a 25% and 50% reduction in disease progression compared to natural history could translate into a present value of cost savings of €33.7B and €72.7B. Halting MCI-AD progression for 3 years with no therapeutic effect thereafter resulted in a present value cost savings of €84.7B in savings. Conclusions: Our data further suggest that early intervention via disease-modifying therapies or lifestyle-based modifications in AD could result in cost savings for society. Additionally, our findings reinforce the importance of accounting for the full value of innovative interventions, management and care paradigms, including their potential impact on direct, indirect and intangible costs impacting patients, their care partners and health and social care systems.

Left atrial ejection fraction is an indicator of left ventricular diastolic function.

Left atrial ejection fraction (LAEF) has been previously shown to accurately distinguish between patients with and without clearly defined left ventricle diastolic dysfunction (LVDD) by ASE/EACVI criteria, but indeterminate cases were excluded. We sought to determine if LAEF could accurately distinguish between normal, indeterminate and LVDD patients. A retrospective cohort of 125 patients who underwent transthoracic echocardiography was studied. Comprehensive echocardiographic study was performed with measurement of validated diastolic parameters. Subjects were assigned LVDF ASE/EACVI categories. ANOVA test was used to compare means between groups and binary logistic regression and ROC curves to assess diagnostic accuracy. Mean LAEF was statistically different between groups (p < 0.001): 56.3% ± 4.5 for normal patients, 50.2% ± 5.5 for indeterminate patients and 44% ± 8.5 for patients with LVDD. LAEF distinguished LVDD from patients without diastolic dysfunction (OR = 0.73, 95% CI 0.63-0.65, p < 0.001) and ROC curve reveals excellent discriminative power (AUC 0.91, 95% CI 0.84-0.97, p < 0.001). LAEF also distinguished indeterminate patients from LVDD (OR = 0.9, 95% CI 0.83-0.95, p < 0.001) and ROC curve revealed good discriminative power (AUC 0.72, 95% CI 0.62-0.82, p < 0.001). LAEF can accurately differentiate between normal, indeterminate and LVDD patients and could be considered as an additional parameter in the study of diastolic function.

Phase I safety and immunogenicity study of a Brazilian serogroup B vaccine.

Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18-44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 µg, 25 µg and 50 µg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies.

Light management with quantum nanostructured dots-in-host semiconductors.

Insightful knowledge on quantum nanostructured materials is paramount to engineer and exploit their vast gamut of applications. Here, a formalism based on the single-band effective mass equation was developed to determine the light absorption of colloidal quantum dots (CQDs) embedded in a wider bandgap semiconductor host, employing only three parameters (dots/host potential barrier, effective mass, and QD size). It was ascertained how to tune such parameters to design the energy level structure and consequent optical response. Our findings show that the CQD size has the biggest effect on the number and energy of the confined levels, while the potential barrier causes a linear shift of their values. While smaller QDs allow wider energetic separation between levels (as desired for most quantum-based technologies), the larger dots with higher number of levels are those that exhibit the strongest absorption. Nevertheless, it was unprecedently shown that such quantum-enabled absorption coefficients can reach the levels (104-105 cm-1) of bulk semiconductors.