Global Measures Research Articles

Offering an auto-play feature likely increases total gambling activity at online slot-machines: preliminary evidence from an interrupted time series experiment at a real-life online casino.

Auto-play is a ubiquitous feature in online casino gambling and virtual slot machines especially, allowing gamblers to initiate spin sequences of pre-set length and value. While theoretical accounts diverge on the hypothesized causal effect on gambling behavior of using the auto-play feature, observational findings show that this feature is used to a higher degree by problem and/or high-intensity gamblers, suggesting that banning this feature may constitute a global responsible gambling measure. Direct, experimental research on causal effects of offering auto-play at online casinos is however lacking. Here, we report the findings of an interrupted time series experiment, conducted at a real-life online casino in Sweden, in which the auto-play feature was made available during a pre-set duration on 40 online slot machines, with 40 matched slots serving as control. Aggregated time series on daily betted amount, spins and net losses were analyzed using a structural Bayesian framework that compared observed developments during the peri-intervention period to modeled counterfactual estimates. Results suggest that offering an auto-play feature on online casinos likely increases total gambling activity in terms of betted amount (approx.+ 7-9%) and (perhaps) number of spins (approx. +3%) but has no effect on net losses. Limitations of studying auto-play effects on a population-level, as well as the complexities of banning this feature within a complex ecosystem of non-perfect channelization to licensed providers, are discussed, including suggestions for future research.

A City-Wide Emissions Inventory of Plastic Pollution.

A global agreement on plastic should have quantitative reduction targets for the emissions of plastic pollution and regular measurements to track success. Here, we present a framework for measuring plastic emissions, akin to greenhouse gas emissions, and demonstrate its utility by calculating a baseline measurement for the City of Toronto in Ontario, Canada. We identify relevant sources of plastic pollution in the city, calculate emissions for each source by multiplying activity data by emission factors for each source, and sum the emissions to obtain the total annual emissions of plastic pollution generated. Using Monte Carlo simulations, we estimate that 3,531 to 3,852 tonnes (T) of plastic pollution were emitted from Toronto in 2020. Littering is the largest source overall (3,099 T), and artificial turf is the largest source of microplastic (237 T). Quantifying source emissions can inform the most effective mitigation strategies to achieve reduction targets. We recommend this framework be scaled up and replicated in cities, states, provinces, and countries around the world to inform global reduction targets and measure progress toward reducing plastic pollution.

Large-Eddy Simulation Study of Injector Geometry and Parcel Injection Location on Spray Simulation of the Engine Combustion Network Spray G Injector

Abstract Recent improvements in computing power and numerical techniques have enabled us resolve minute details of spray plume behavior and its wall boundary interactions, and made detailed spray simulations using large-eddy simulation (LES) turbulence models available to many more engineers. However, guidelines for parcel-based spray simulation boundary and initial conditions are still based on results from lower-resolution and Reynolds averaged Navier–Stokes (RANS) simulations. Hence, it is necessary to critically examine those assumptions and compare their impact with results using a RANS turbulence model. Three different parameters, including whether a simulation includes a detailed injector tip geometry or a flat surface, whether parcels are initialized at the counterbore exit, which is more common, or at the nozzle exit, and whether to use an experimentally derived rate of injection or one-way coupling with a separate internal nozzle volume of fluid simulation, were examined with an LES turbulence model. Both local data close to the injector and global penetration results were used to compare simulations. Local data, such as the local liquid volume fraction, showed greater variation between the conditions, which may have an impact on mixing and combustion predictions in engine applications. Spray penetration and other global measures demonstrated limited sensitivity to the boundary conditions/initialization procedure. Results were also compared with prior results that used a RANS turbulence model. RANS simulations had overall smoother responses to the changes, as would be expected, but LES simulations showed similar trends in the effects for the measured variables.

Can microvascular damage predict disease severity in patients with systemic sclerosis?

IntroductionSystemic sclerosis (SSc) is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC). Materials and methodsA retrospective study of patients with SSc and a NVC performed within the first 6 months after diagnosis was conducted. Visceral involvement in the first 3 years of the disease and NVC findings were collected. The severity of microvascular damage was classified into four categories, according to the worsening of the NVC patterns. The severity of organ involvement was assessed by the disease severity scale of Medsger for each organ and as a global measure of disease severity, the simple summation was used. ResultsA total of 86 patients with SSc were included. A moderate correlation was found between the severity of microvascular damage and the global measure of disease severity (r=0.55, p<0.001), the severity of peripheral vascular involvement (r=0.43, p<0.001) and the severity of skin involvement (r=0.34, p=0.001).The presence of a late scleroderma pattern in NVC were predictive in univariate analysis of digital ulcers (OR 6.03, 95% CI 1.52–23.86, p=0.01), muscular involvement (OR 13.09, 95% CI 1.09–156.78, p=0.04), calcinosis (OR 27.22, 95% CI 5.56–133.33, p<0.001) and worse global disease severity score (OR 1.67, 95% CI 1.17–2.38, p=0.005). Multivariate analysis adjusted for disease duration and gender confirmed late pattern as an independent predictor of calcinosis (OR 42.89, 95% CI 5.53–332.85, p<0.001). Discussion and conclusionIn this study, the worsening of NVC pattern in SSc was associated with the overall disease severity, the severity of peripheral vascular involvement and extension of skin involvement. This study highlights the importance of NVC as a prognostic tool and a possible predictor of systemic visceral involvement.

Abstract WP220: Structural Connectivity Injury is Associated With Poor Language Outcomes in Perinatal Stroke

Introduction: Perinatal stroke refers to brain injury sustained between 28 weeks of gestational age (GA) and 28 days of life. Stroke risk in the newborn period is significantly higher relative to other life stages, and over half of all survivors endure lifelong neurological sequalae. Language deficits are observed in many patients, can emerge at any stage in development, and are difficult to predict. Lesion laterality and location are not sufficient to explain language outcomes in a rapidly developing brain with capacities for reassignment of functions to non-injured structures. Structural connectivity studies describe a “rich club” organization of the brain with 6 bilateral highly connected anatomical structures that form the information backbone for all networks. This organization has been found to exist as early as 30 weeks GA. The effects of injury to this rich club have been studied in adult stroke patients with respect to stroke severity and outcome. Given that language is a network function, we hypothesized that injury to rich club regions - a measure of structural network disruption - is associated with poor language outcomes in perinatal stroke. Methods: Retrospective study that identified perinatal stroke patients in a pediatric stroke clinic database. Clinical and imaging data retrieved included brain MRI scans and longitudinal scores of standardized neuropsychological tests. Multiple linear regression models were created for the following variables: age, sex, Autism Spectrum Disorder diagnosis, lesion volume (cm 3 ), and number of rich clubs affected by the stroke. All analyses were conducted using the computing environment R. Significance was set at p &lt; 0.05. Results: Cohort of 75 patients was identified. Median time to follow up was 7 years, and median time between the first and last test was 30 months. Lesion volume significantly influenced receptive language outcomes at younger ages (beta = -0.446), however the number of rich clubs affected by the injury was the only significant variable associated with a poor expressive language outcome at follow-up (beta = -0.699). Discussion: Number of rich clubs affected by injury, as a global measure of structural network disruption in the neonatal period, can be used to inform language outcome prognostication.

Executive functions assessment in very preterm children at school age: A pilot study about a clinical and experimental approach

While the survival rate of very preterm (VPT) infants has increased in the last decades, they are still at risk of developing long-term neurodevelopmental impairments, especially regarding self-regulatory abilities, and goal-directed behaviors. These skills rely on executive functions (EFs), an umbrella term encompassing the core capacities for inhibition, shifting, and working memory. Existing comprehensive tests are time-consuming and therefore not suitable for all pediatric neuropsychological assessments. The Flanker task is an experimental computer game having the advantage to last less than ten minutes while giving multiple EFs measures. Here, we tested the potency of this task in thirty-one VPT children aged 8–10 years during their clinical assessment. First, we found that VPT children performed in the norm for most clinical tests (i.e., WISC-V, BRIEF, and NEPSY) except for the CPT-3 where they were slower with more omission errors, which could indicate inattentiveness. Second, some Flanker task scores were correlated with standardized clinical testing without resisting to multiple comparisons correction. Finally, compared to full-term children, VPT children showed poorer performance in global EFs measure and lower accuracy in the Flanker task. These findings suggest that this child-friendly version of the Flanker task demonstrated a reasonable sensitivity in capturing EFs with good discrimination between VPT and term children despite VPT children’s mild difficulties. It may represent a promising tool for neuropsychological assessments and be suitable as a screening test, providing further validating larger studies. Moreover, while VPT schoolchildren globally display normal intelligence, subtle difficulties that seem to relate to EFs are observed.

Vortioxetine Treatment for Depression in Patients with Prodromal vs Mild Alzheimer’s Disease: A Six-Month, Open-Label, Observational Study

BackgroundDepressive symptoms are common in Alzheimer disease (AD) from the prodromal stage. The benefits of antidepressants have been investigated in patients with AD dementia with mixed results.ObjectivesThis study aimed to compare the efficacy of vortioxetine in prodromal and mild-to-moderate AD patients with depression, and to assess the comparative effect on secondary measures, including behavioral disturbances, cognitive function, and activities of daily living.ParticipantsAll subjects with AD at a single-center dementia center underwent a standard evaluation with mini-mental state examination (MMSE), basic and instrumental activities of daily living (BADL and IADL), geriatric depression scale (CDS), neuropsychiatrie inventory (NPI), and clinical evaluation every six months.MeasurementsThe study specifically assessed patients on vortioxetine with available six-month follow-up data. The changes in CDS, NPI, MMSE, BADL/IADL at six months in the entire AD population and mild-to-moderate AD vs prodromal population were analyzed using repeated measure multivariate analyses. Linear regression analyses were implemented to evaluate baseline demographics and clinical characteristics associated with depressive and cognitive improvements at six months.ResultsOut of 680 AD patients, 115 were treated with vortioxetine, and 89 with six-month follow-up data were included in the analyses. A significant improvement at follow-up was observed for CDS, NPI total and sub score items (mood, anxiety, apathy, sleep disturbances, eating abnormalities). Both mild-to-moderate and prodromal AD showed a positive CDS response, whereas mild-to-moderate AD showed a better improvement on total NPI and apathy/nighttime behaviors subitems compared to prodromal AD. Higher baseline CDS score was the only variable associated with higher responses in linear regression analyses. MMSE showed a significant improvement at six months in the entire cohort, with a greater effect in prodromal vs mild-to-moderate AD. Cognitive improvement (i.e., MMSE changes) was associated with cognitive status at baseline but independent of the antidepressant/behavioral changes (i.e., GDS/NPI).ConclusionsOur results suggest that vortioxetine is highly tolerable and clinically effective in both prodromal and mild-to-moderate AD with depression. Patients with mild-to-moderate AD benefited more from a wide range of behavioral disturbances. The study also showed significant improvement in global cognitive measures, especially in prodromal AD subjects. Further studies are needed to investigate the independent beneficial effect of vortioxetine on depression and cognition in AD.

Associations of carotid atherosclerosis with cognitive function and brain health: Findings from a UK tri-ethnic cohort study (Southall and Brent Revisited)

BackgroundCognitive function has an important role in determining the quality of life of older adults. Cardiovascular disease (CVD) is common in older people and may compromise cognitive performance; however, the extent to which this is related to carotid atherosclerosis is unclear. AimWe investigated associations between carotid atherosclerosis and cognitive function and neuroimaging markers of brain health in a UK multi-ethnic community-based sample including older people of European, South Asian, and African-Caribbean ethnicity. MethodsCarotid plaques and intima-media thickness (cIMT) were assessed using ultrasound in 985 people (mean age 73.2y, 56 % male). Associations of carotid atherosclerosis with cognitive function (memory, executive function, language and CSI-D, a global measure of cognitive state) and neuroimaging measures (total brain volume, hippocampal volume, white matter (WM) lesion volume and coalescence score) were analysed using regression analyses, with and without adjustment for potential confounders using two models: 1) adjustment for age, sex, and ethnicity; 2) model 1 plus education, physical activity category, body mass index, hypertension, diabetes, total and high density lipoprotein cholesterol, atrial fibrillation, smoking, previous CVD, alcohol consumption, and presence of chronic kidney disease. ResultsPeople with carotid plaque or higher cIMT had lower CSI-D score, poorer memory poorer executive function and higher WM lesion volume and coalescence. Language was poorer in people with plaque but was not correlated with cIMT. Associations with plaque were preserved after full adjustment (model 2) but relationships for cIMT were attenuated. Associations with other plaque characteristics were generally unconvincing after adjustment. ConclusionsThis multi-ethnic cohort study provides evidence that presence of carotid plaque, is associated with poorer cognitive function and brain health.

Derivative-Variance Hybrid Global Sensitivity Measure with Optimal Sampling Method Selection

This paper proposes a derivative-variance hybrid global sensitivity measure with optimal sampling method selection. The proposed sensitivity measure is as computationally efficient as the derivative-based global sensitivity measure, which also serves as the conservative estimation of the corresponding variance-based global sensitivity measure. Moreover, the optimal sampling method for the proposed sensitivity measure is studied. In search of the optimal sampling method, we investigated the performances of six widely used sampling methods, namely Monte Carlo sampling, Latin hypercube sampling, stratified sampling, Latinized stratified sampling, and quasi-Monte Carlo sampling using the Sobol and Halton sequences. In addition, the proposed sensitivity measure is validated through its application to a rural bridge.

Perceived competence in ice hockey and its associations with relative age, early sport specialization, and players’ position

IntroductionIce hockey is a sport that has gained much attention in recent times, particularly concerning the development of young players. In the domain of youth sport development, one significant factor that must be considered is the perceived competence of players. This variable is closely linked to positive psychological outcomes and sustained practice. However, there is a lack of understanding about how other important developmental factors such as age, early sport specialization, players’ position and relative age affect players’ perceived competence. Therefore, the objective of this study is to explore the relationships between these developmental factors, perceived ice hockey competence and a global measure of perceived sport competence.MethodsData was drawn from 971 players (14.78 ± 1.61 mean age), who completed on-line questionnaires, from which we conducted path analyses involving all variables.ResultsYounger players tend to display higher perceived competence scores than older players. Additionally, players who opted to specialize earlier also reported higher perceived competence. Furthermore, forwards and defensemen had differing perceptions of their competence, which was in line with their respective roles on the ice. The study also showed relative age effects, in which players who were born earlier relative to the selection period tend to perceive themselves more advantageously in three components of perceived competence.DiscussionBased on these findings, several recommendations are proposed for coaches and decision-makers to encourage the positive development of ice hockey players. The study highlights that ice hockey-specific competencies are influenced by various factors, such as early sport specialization, relative age effect, player age, and position.

The Development and Psychometric Evaluation of the Sexual Fantasy Experience Scale.

Clinicians and researchers consider sexual fantasies to be a central aspect of human sexuality. Although these are subjective experiences, most studies have assessed only their frequency and content. A measure that assesses individuals' subjective experience of sexual fantasies is therefore needed. The aim of this study was to evaluate the psychometric properties of a new measure, the Sexual Fantasy Experience Scale (SFES). In Study 1, the SFES was administered to 391 participants (240 defined themselves as women, 149 as men, and2 as other). In Study 2, the SFES was administered to 426 participants (255 defined themselves as women,167 as men, and 4 as other), along with a battery of questionnaires including the New Sexual Satisfaction Scale Short Form and the Global Measure of Sexual Satisfaction, both of which measure sexual satisfaction, as well as the Sexual Fantasy Checklist, which evaluates the content of sexual fantasies and their frequency. Five reliable SFES subscales emerged from Study 1: playfulness, limitlessness, functionality, intrusiveness, and shame. In Study 2, a confirmatory factor analysis confirmed the scale's underlying factor structure, which was obtained in Study 1. The subscales of the SFES contributed to the explained variance of the assessments of sexual satisfaction, beyond the contribution of the fantasies' content and frequency, demonstrating the incremental validity of the subscales. The results of the present analyses suggest that the SFES has good psychometric properties, making it useful as an assessment tool for future research, clinical practice, and sex education.

Abnormal developmental of structural covariance networks in young adults with heavy cannabis use: a 3-year follow-up study

Heavy cannabis use (HCU) exerts adverse effects on the brain. Structural covariance networks (SCNs) that illustrate coordinated regional maturation patterns are extensively employed to examine abnormalities in brain structure. Nevertheless, the unexplored aspect remains the developmental alterations of SCNs in young adults with HCU for three years, from the baseline (BL) to the 3-year follow-up (FU). These changes demonstrate dynamic development and hold potential as biomarkers. A total of 20 young adults with HCU and 22 matched controls were recruited. All participants underwent magnetic resonance imaging (MRI) scans at both the BL and FU and were evaluated using clinical measures. Both groups used cortical thickness (CT) and cortical surface area (CSA) to construct structural covariance matrices. Subsequently, global and nodal network measures of SCNs were computed based on these matrices. Regarding global network measures, the BL assessment revealed significant deviations in small-worldness and local efficiency of CT and CSA in young adults with HCU compared to controls. However, no significant differences between the two groups were observed at the FU evaluation. Young adults with HCU displayed changes in nodal network measures across various brain regions during the transition from BL to FU. These alterations included abnormal nodal degree, nodal efficiency, and nodal betweenness in widespread areas such as the entorhinal cortex, superior frontal gyrus, and parahippocampal cortex. These findings suggest that the topography of CT and CSA plays a role in the typical structural covariance topology of the brain. Furthermore, these results indicate the effect of HCU on the developmental changes of SCNs in young adults.

Altered grey matter structural covariance in chronic moderate–severe traumatic brain injury

Traumatic brain injury (TBI) alters brain network connectivity. Structural covariance networks (SCNs) reflect morphological covariation between brain regions. SCNs may elucidate how altered brain network topology in TBI influences long-term outcomes. Here, we assessed whether SCN organisation is altered in individuals with chronic moderate–severe TBI (≥ 10 years post-injury) and associations with cognitive performance. This case–control study included fifty individuals with chronic moderate–severe TBI compared to 75 healthy controls recruited from an ongoing longitudinal head injury outcome study. SCNs were constructed using grey matter volume measurements from T1-weighted MRI images. Global and regional SCN organisation in relation to group membership and cognitive ability was examined using regression analyses. Globally, TBI participants had reduced small-worldness, longer characteristic path length, higher clustering, and higher modularity globally (p < 0.05). Regionally, TBI participants had greater betweenness centrality (p < 0.05) in frontal and central areas of the cortex. No significant associations were observed between global network measures and cognitive ability in participants with TBI (p > 0.05). Chronic moderate–severe TBI was associated with a shift towards a more segregated global network topology and altered organisation in frontal and central brain regions. There was no evidence that SCNs are associated with cognition.

GLFNet: Combining Global and Local Information in Vehicle Re-Recognition.

Vehicle re-identification holds great significance for intelligent transportation and public safety. Extracting vehicle recognition information from multi-view vehicle images has become one of the challenging problems in the field of vehicle recognition. Most recent methods employ a single network extraction structure, either a single global or local measure. However, for vehicle images with high intra-class variance and low inter-class variance, exploring globally invariant features and discriminative local details is necessary. In this paper, we propose a Feature Fusion Network (GLFNet) that combines global and local information. It utilizes global features to enhance the differences between vehicles and employs local features to compactly represent vehicles of the same type. This enables the model to learn features with a large inter-class distance and small intra-class distance, significantly improving the model's generalization ability. Experiments show that the proposed method is competitive with other advanced algorithms on three mainstream road traffic surveillance vehicle re-identification benchmark datasets.

The Protective Effect of Serum Levels of Vitamins C, D, and E and IgG and IgM Antibodies in Individuals Vaccinated Against COVID-19 and Experienced Disease Relapse

Background: Despite global control measures aimed at ending the COVID-19 pandemic, the disease continues to pose a threat to public health. In this study, we examined the serum levels of vitamins C, D, and E, as well as IgG and IgM antibodies in individuals who had previously been vaccinated against COVID-19 and subsequently experienced a relapse of the disease. Objectives: The objective of this study was to investigate the correlation between sufficient levels of vitamins E, D, and C, the severity of the disease, and the immunological response in vaccinated patients who have experienced a recurrence of COVID-19. Methods: Given the potential role of vitamins C, D, and E in the management of COVID-19, we conducted a study to examine the serum levels of these vitamins in individuals who had previously been vaccinated against COVID-19 and experienced a disease relapse, characterized by symptoms, such as body pain, shortness of breath, cough, and fever. We compared two groups of hospitalized individuals with varying disease severity to healthy individuals. Additionally, we investigated IgG and IgM antibodies in these patients due to the significance of antibody levels in determining disease severity. Results: Our results revealed significant differences in the levels of vitamins C, D, and E between hospitalized individuals and healthy individuals. Furthermore, a notable disparity in serum IgM and IgG levels was observed based on the severity of the disease. However, no significant difference was detected in the average levels of anti-SARS-CoV-2 immunoglobulins among the different groups, whether they had received the AstraZeneca or Sinopharm vaccines. Conclusions: Vitamins C, D, and E play supportive roles in the immune system, aiding the host's immune response. These findings suggest that maintaining adequate levels of these vitamins may be beneficial in preventing SARS-CoV-2 reinfection and reducing disease severity, particularly in cases where vaccine efficacy is uncertain.

An exploratory study of longitudinal trajectory of language, swallowing and cognition post endovascular clot retrieval.

Endovascular clot retrieval (ECR) is known to reduce global disability at 3 months post stroke however limited research exists regarding the trajectory of specific clinical impairments including language, swallowing and cognitive deficits between onset and 3 months. To assess language, swallowing, and cognitive performance following ECR and explore whether impairment severity is correlated with modified Thrombolysis in Cerebral Infarction score (mTICI), stroke severity or quality of life (QoL). Assessment was completed within 7 days (T1), 1 month (T2) and 3 months (T3) post-stroke. Performance was measured with the Functional Oral Intake Scale (FOIS), Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Trail Making Test (TMT A and B) and Brixton Spatial Awareness Test. The Western Aphasia Battery (WAB) was used for left hemisphere stroke. QoL was measured with the Stroke and Aphasia Quality of Life Scale. Twenty-five participants (median 72 years; 64% male) were prospectively recruited following ECR. High reperfusion success (68% mTICI 3) and low stroke severity post ECR (median 24h NIHSS = 3, IQR 7-18) were noted. At T1, 10 participants presented with aphasia, eight required a modified diet and 20 had impaired cognition. At T3 all had recovered to a normal oral diet, 39% had persistent cognitive impairment and 45% of patients with left hemisphere stroke remained aphasic. Performance on the WAB, FOIS, RBANS and TMT changed significantly over time (all p<0.05). The severity score at T1 for all measures, excluding TMT B and Brixton, was significantly correlated with 24h NIHSS. WAB scores at T3 were correlated with QoL (r = 0.618; p = 0.043). This exploratory study found the longitudinal performance of language, swallowing and cognition significantly improved over time and severity in the first-week post-ECR was correlated with 24h NIHSS rather than the degree of reperfusion. What is already known on the subject Randomised control trials have demonstrated the benefit of ECR in patients with ischemic stroke using global measures of disability and function. Limited research exists regarding the trajectory of specific clinical impairments including language, swallowing and cognitive deficits. There is also a reliance on screening assessments and a lack of consideration of the influence of co-occurring impairments. What this paper adds to existing knowledge This prospective study is amongst the first to explore the longitudinal trajectory of language, swallowing and cognitive impairment using a standardised assessment battery. Twenty-four-hour NIHSS was significantly correlated with language, swallowing, global cognition and some measures of executive function. Language performance post ECR was correlated with domain-specific cognitive assessment of attention, immediate memory and delayed memory, which differed from swallowing performance post ECR that correlated with measures of executive function. What are the potential or actual clinical implications of this work? It is important for speech-language pathologists and the wider medical team to monitor language, swallowing and cognitive performance post ECR regardless of treatment success. Stroke severity at 24h post-ECR influences the severity of language, swallowing and cognitive impairments.

A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol

BackgroundGlioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma.Methods/designGLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland.Trial registrationNCT05664464. Registered 23 December 2022.

Mapping of the PROMIS global health measure to the PROPr in the United States

BackgroundThe Patient-Reported Outcomes Measurement and Information System (PROMIS®) global health items (global-10) yield physical and mental health scale scores and the PROMIS-Preference (PROPr) scoring system estimated from PROMIS domain scores (e.g., PROMIS-29 + 2) produces a single score anchored by 0 (dead or as bad as being dead) to 1 (full health). A link between the PROMIS global-10 and the PROPr is needed.MethodsThe PROMIS-29 + 2 and the PROMIS global-10 were administered to 4102 adults in the Ipsos KnowledgePanel in 2022. The median age was 52 (range 18–94), 50% were female, 70% were non-Hispanic White, and 64% were married or living with a partner. The highest level of education completed for 26% of the sample was a high school degree or general education diploma and 44% worked full-time. We estimated correlations of the PROPr with the PROMIS global health items and the global physical and mental health scales. We examined the adjusted R2 and estimated correlations between predicted and observed PROPr scores.ResultsProduct-moment correlations between the PROMIS global health items and the PROPr ranged from 0.50 to 0.63. The PROMIS global physical health and mental health scale scores correlated 0.74 and 0.60, respectively, with the PROPr. The adjusted R2 in the regression of the PROPr on the PROMIS global health items was 64%. The equated PROPr preference scores correlated (product-moment) 0.80 (n = 4043; p < 0.0001) with the observed PROPr preference scores, and the intra-class correlation (two-way random effects model) was 0.80. The normalized mean absolute error (NMAE) was 0.45 (SD = 0.43). The adjusted R2 in the OLS regression of the PROPr on the PROMIS global health scales was 59%. The equated PROPr preference scores correlated (product-moment) was 0.77 (n = 4046; p < 0.0001) with the observed PROPr preference scores, and the intra-class correlation was 0.77. The NMAE was 0.49 (SD = 0.45).ConclusionsRegression equations provide a reasonably accurate estimate of the PROPr preference-based score from the PROMIS global health items or scales for group-level comparisons. These estimates facilitate cost-effectiveness research and meta-analyses. The estimated PROPr scores are not accurate enough for individual-level applications. Future evaluations of the prediction equations are needed.

Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice.

Advancing age is the strongest risk factor for osteoporosis and skeletal fragility. Rapamycin is an FDA-approved immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) complex, extends lifespan, and protects against aging-related diseases in multiple species; however, the impact of rapamycin on skeletal tissue is incompletely understood. We evaluated the effects of a short-term, low-dosage, interval rapamycin treatment on bone microarchitecture and strength in young-adult (3 mo old) and aged female (20 mo old) C57BL/6 mice. Rapamycin (2mg/kg body mass) was administered via intraperitoneal injection 1×/5d for a duration of 8wk; this treatment regimen has been shown to induce geroprotective effects while minimizing the side effects associated with higher rapamycin dosages and/or more frequent or prolonged delivery schedules. Aged femurs exhibited lower cancellous bone mineral density, volume, trabecular connectivity density and number, higher trabecular thickness and spacing, and lower cortical thickness compared to young-adult mice. Rapamycin had no impact on assessed microCT parameters. Flexural testing of the femur revealed that both yield strength and ultimate strength were lower in aged mice compared to young-adult mice. There were no effects of rapamycin on these or other measures of bone biomechanics. Age, but not rapamycin, altered local and global measures of bone turnover. These data demonstrate that short-term, low-dosage interval rapamycin treatment does not negatively or positively impact the skeleton of young-adult and aged mice.

Green growth assessment across 203 economies: Trends and insights

Green growth underpins the achievement of sustainable transition through continued economic development while addressing threats to environmental sustainability and socially inclusive well-being. Yet, decoupling economic growth from natural resource depletion and environmental degradation while achieving long-term sustainable development remains complex. Here, we present a comprehensive evaluation of green growth across 203 economies using our novel dataset (i.e., Data descriptor titled, “Comprehensive green growth indicators across countries and territories” published in Scientific Data) to examine the determinants and indicators of green growth and their variations across diverse countries and regions. We further analyze the long-term trends and patterns of green growth performance, drawing insights from historical data for future policy-making. Finally, we examine the policy implications of β-convergence in green growth while addressing regional disparities. We use the constructed global measures of green growth to rank (winners and losers) countries with environmentally sustainable economic development. The top ten economies with high performance in green growth include Monaco, Singapore, New Zealand, New Caledonia, American Samoa, the US, Japan, Bangladesh, Sri Lanka, and Australia. In contrast, the bottom ten economies ranked by their low green growth performance include Saint Martin, Faeroe Islands, Turkmenistan, Sint Maarten, Palau, Guinea-Bissau, Sierra Leone, Bermuda, Suriname, and Curacao in a bottom-up fashion. Our empirical results show that green growth policies that internalize the negative effects of sustainable development improve a country's socioeconomic dynamics, environmental quality of life, natural asset base, policy responses, and emission productivity.