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Unexpected danger lurks in this giant fault in the Yukon

Synthesis, physical properties, and root canal sealing of experimental MTA- and salicylate-based root canal sealers

Objectives To develop and evaluate the physical properties and sealing ability within the root canal of three experimental sealers based on MTA and a salicylate resin. Materials and methods The experimental sealers were composed of two pastes. The base paste was prepared using 1,3-butyleneglycol disalicylate and bismuth oxide. Three different catalytic pastes were formulated, creating three groups: [MTA] n,n,dihydroxyethyl-p-toluidine (DPT), titanium dioxide (TiO2), and mineral trioxide aggregate (MTA); [MTA-HA] DPT + TiO2 + MTA + hydroxyapatite (HA); and [MTA-DCPD] DPT + TiO2 + MTA + dibasic calcium phosphate dihydrate (DCPD). MTA Fillapex (Angelus) was used as the commercial reference (control). The sealers were manipulated at a 1:1 ratio (base paste:catalyst). Tests for working time and setting time, flow, and film thickness were conducted following ISO 6876:2012 standards. Single-rooted human teeth root canals were utilized for evaluating root canal filling using micro-computed tomography, push-out bond strength testing, and sealer penetration into dentinal tubules using confocal microscopy. Failure patterns in the push-out test were classified as adhesive, cohesive, or mixed. Sealer micromorphology was analyzed via scanning electron microscopy. Data were analyzed statistically (α = 0.05). Results MTA Fillapex showed the longest working and setting times, highest flow, the lowest film thickness, and better penetration into dentinal tubules. There was no difference in void among evaluated sealers. Overall, MTA-DCPD sealer showed the lowest bond strength values for cervical and apical thirds. Micromorphological analysis revealed similar crystallographic properties among all sealers. Conclusions The sealers tested showed reduced working and setting times, with flow and film thickness according to ISO 6876:2012. Their void volume and bond strength were similar to MTA Fillapex, except for MTA-DCPD. Clinical Relevance: The experimental root canal sealers demonstrated suitable physical properties and good adaptation within the root canal.

Experience of clinical incivility and stress in nursing students: A mixed-method study

Nursing students often experience uncivil words or actions during clinical practice which can lead to significant stress. The purpose of our study was to quantitatively investigate the degree of clinical incivility and stress experienced by students and the statistical relationship between them and qualitatively explore students’ personal experiences of clinical incivility and stress. Our study was conducted from April 25 to May 27, 2023, using a mixed-method design. Phase One, the quantitative component, used a non-experimental, descriptive, cross-sectional study design with a 10-minute self-administered online survey. Phase Two, the qualitative component, used an in-person focus group to collect data on participants’ personal experiences of clinical incivility and stress. A total of 159 junior and senior pre-licensure nursing students attending a clinical practicum of a Bachelor of Science in Nursing (BSN) program in South Korea completed the quantitative online survey. Subsequently, 20 students voluntarily attended focus group sessions. To analyze the online survey data the study sample was divided into a clinical incivility group and a non-clinical incivility group. A group comparative analysis using chi-square and t-test was conducted. To analyze the qualitative focus group data, Colaizzi’s method to identify significant themes was used. Prevalence of clinical incivility experience in the students was 79.9% (n = 123 out of 159). Clinical incivility was significantly positively correlated with the students’ reported stress level (r = .317, p < .001); students who experienced greater clinical incivility reported higher levels of stress. Additionally, higher levels of clinical incivility were linked to lower levels of satisfaction with clinical practice and the clinical site. Analysis of the focus group data revealed four main themes regarding the students’ experiences: 1) Being defenselessly exposed to verbal or nonverbal abuse, 2) Not being treated as a student nurse, 3) Experiencing a combination of negative feelings, and 4) Taking incivility for granted in the clinical site. Major perpetrators of clinical incivility among nursing students were nurses at the clinical sites. To prevent and manage clinical incivility, nursing schools and clinical agencies must collaborate to establish incivility monitoring, communication, and evidence-based policies and intervention programs.

Controversial ‘arsenic life’ paper retracted after 15 years — but authors fight back

Protein-primed homopolymer synthesis by an antiviral reverse transcriptase

Genetic diversity and evolutionary insights of Dali tea (Camellia taliensis) in the Lancang River Basin: Implications for tea breeding and resource conservation

Dali tea (Camellia taliensis), serving as a primitive wild species within the section Thea, represents a crucial genetic source for the domestication of Pu-erh tea (C. sinensis var. assamica) due to its strong stress tolerance and unique biochemical composition. It is of key value for the conservation of tea genetic resources and breeding innovation. Utilizing the SLAF-seq (Specific-Locus Amplified Fragment Sequencing) technique, this study systematically analyzed the genetic diversity and evolutionary relationships among five geographic populations (16 C. taliensis and 4 C. sinensis var. assamica accessions) within the Lancang River basin. Results revealed significant genetic differentiation among the C. taliensis populations. Pronounced genetic isolation was observed between the Lincang Daxueshan and Dali Nanjian populations. Localized gene introgression occurred between wild C. taliensis (Nanjian population) and C. sinensis var. assamica.The wild Lincang Daxueshan population formed a monophyletic clade at the base of the phylogenetic tree, exhibiting strong genetic isolation and high differentiation levels (Fst = 0.364) but low genetic diversity. In contrast, the cultivated population (Banna Germplasm Repository) displayed a mixed genetic background, with wild genetic components constituting only 50%−60%. The Lincang Daxueshan wild population showed a low minor allele frequency (MAF = 0.204) and a mild inbreeding coefficient (Fis = 0.09), indicating a potential risk of genetic erosion. Conversely, the Banna Germplasm Repository population exhibited the highest genetic diversity (Shannon Index = 0.318), highlighting the effectiveness of ex situ conservation and its potential as a vital gene donor for tea breeding. This study underscores the unique status of the upper Lancang River basin in Yunnan as a core conservation area for C. taliensis genetic diversity. We propose strategies of “delineating priority zones for in situ conservation” and “facilitating inter-population germplasm exchange,” providing a molecular basis for conserving wild tea resources and breeding for stress resistance. Employing high-density SNP markers, we obtained 5,182,931 loci with an average sequencing depth of 19.30x. This enabled quantification of gene flow between wild and cultivated populations (Nm = 0.18) and clarified the contribution of introgressive domestication to the genetic makeup of cultivated tea. These findings provide a theoretical foundation for understanding interspecific interaction mechanisms in tea plant evolution and hold significant implications for promoting regional ecological conservation and biodiversity maintenance.

Apparent differences between human and chimp proteomes are reduced when considering human population: Human specific variants are enriched in disordered and compositionally biased regions

Humans exhibit significant differences from other primates in anatomy, physiology, behavior, and culture, despite having similar genomes. Understanding the genetic basis of these unique human traits has long been a goal of science and philosophy. Previous studies, including the comparison of the reference genomes, showed a high degree of sequence identity between the proteomes of humans and chimpanzees (Pan troglodytes), suggesting that differences may lie in gene regulation rather than protein function. To pinpoint human-specific protein mutations with possible relevance for human-specific traits, we went further in the study of human-chimp proteome differences by taking into account human genetic variation data from the Genome Aggregation Database (gnomAD) at protein-coding genes. We additionally included 11 primate genomes to identify human-specific amino acids. Results showed that human-specific positions were dramatically reduced when considering population diversity. Our analysis identified 6210 human-specific amino acid substitutions across 4475 proteins. Interestingly, these residues are enriched on disordered and compositionally biased regions, suggesting a role in protein regulation instead of a catalytic or structural one. Accordingly, the set of proteins holding them was significantly enriched in proteins with disordered regions and with protein binding functions. We found that a subset of these residues is not only different in humans but also conserved across non-human primates, further supporting their potential importance in making us different from other primates.

Surgical workspace in porcine thoracoscopy with two-lung ventilation

In neonatal and pediatric thoracoscopy, two-lung ventilation is often used due to the size constraints of double-lumen tubes or selective bronchial blockers. Reducing the volume of both lungs to create surgical workspace requires moderation in the application of capnothorax insufflation pressures, and requires experienced anesthesiologists to manage ventilation. This balance was investigated in anesthetized pigs in the left decubitus position with a capnothorax, using volume-guaranteed intermittent positive pressure ventilation. End-expiratory computed tomography scans were obtained in 10 pigs (median weight 21.5 kg, range 17.8 to 26.3 kg) during incremental CO2 insufflation pressures of 0, 3, 5, 6, 8 and 10 mmHg. Capnothorax, right lung and left lung volumes were measured. At an insufflation pressure of 10 mmHg, peak ventilation pressures had a median of 35 cmH2O. Insufflation pressures ≥ 6 mmHg had profound cardiorespiratory effects, requiring inotropic support. Capnothorax volume reached a median of 1503 (IQR 1465–1596) ml at 10 mmHg, at which diaphragmatic displacement contributed 79.5% to capnothorax volume, with smaller contributions from lung volume (16.1%) and thoracic expansion (4.4%). Thoracoscopic workspace during two-lung ventilation originates mainly from diaphragmatic displacement. In a porcine model the marked cardiorespiratory consequences of insufflation emphasized the need to minimize insufflation pressures.

Iterative learning control of neuronal firing based on FHN and HR models

Neuronal firing patterns are fundamental to neural information processing and functional regulation, with abnormal firing closely linked to a range of neurological disorders. However, existing neuromodulation techniques largely rely on open-loop stimulation strategies, which lack adaptability and fail to provide precise control over neuronal dynamics. To address this limitation, this study introduces a novel iterative learning control (ILC) framework based on proportional-integral (PI) control for closed-loop modulation of neuronal firing patterns. The proposed method is developed and validated using two representative neuron models: the FitzHugh–Nagumo (FHN) and Hindmarsh–Rose (HR) models. A dynamical analysis of these models is conducted, followed by the design and implementation of a PI-based ILC strategy. Numerical simulations demonstrate that the proposed control method significantly outperforms conventional PI control, achieving lower tracking errors, enhanced control accuracy, and improved system stability. Additionally, the ILC approach exhibits strong adaptability to different neuronal dynamics, highlighting its potential for precise and robust regulation in complex neural systems. These findings offer a theoretical basis for advancing closed-loop neuromodulation technologies, with promising implications for applications in neurorehabilitation and the treatment of neurological disorders.

Evaluating the short-term effects of dance on motor and non-motor outcomes in people living with Parkinson’s: A crossover study

Purpose To investigate the short-term effects of a single dance class on motor and non-motor outcomes in people living with Parkinson’s. Methods A crossover design was used. Nineteen people participated. All participants took part in both dance and lecture control conditions seven days apart in a counterbalanced order. Outcomes of gait, balance, functional mobility, and aspects of cognition were measured before and after each condition. A visual analogue scale evaluated self-perceived changes in fatigue, energy, depression, anxiety, concentration, and movement. Statistical analyses were performed using 2x2 repeated-measures ANOVAs with time (pre vs. post) and condition (dance vs. lecture) as factors. Results Results showed functional mobility (measured by the Timed Up and Go) improved to a greater extent after dance compared to the lecture. Significant improvements after both dance and lecture sessions were demonstrated for other outcomes measuring balance, cognition, and anxiety, indicating either both conditions had a comparable impact or practice effects may have influenced results. Conclusions Further research is needed to confirm the presence and strength of the short-term effect of dance on functional mobility, to assess the impact of dancing on aspects of cognition and anxiety, and to hone the approach to studying the short-term effects of dance.

Estimation of free-roaming dog populations using Google Street View: A methodological study

Controlling and eliminating zoonotic pathogens such as rabies virus, Echinococcus granulosus, and Leishmania spp. require quantitative knowledge of dog populations. Dog population estimates are fundamental for planning, implementing, and evaluating public health programs. However, dog population estimation is time-consuming, requires many field personnel, may be inaccurate and unreliable, and is not without danger. Our objective was to evaluate a remote method for estimating the population of free-roaming dogs using Google Street View (GSV). Adopting a citizen science approach, participants from Arequipa and other regions in Peru were recruited using social media and trained to use GSV to identify and count free-roaming dogs in 20 urban and 6 periurban communities. We used correlation metrics and negative binomial models to compare the counts of dogs identified in the GSV imagery with accurate counts of free-roaming owned dogs estimated via door-to-door (D2D) survey conducted in 2016. Citizen scientists detected 862 dogs using GSV. After adjusting by the proportion of streets that were scanned with GSV we estimated 1,022 free-roaming dogs, while the 2016 D2D survey estimated 1,536 owned free-roaming dogs across those 26 communities. We detected a strong positive correlation between the number of dogs detected by the two methods in the urban communities (r = 0.85; p < 0.001) and a weak correlation in periurban areas (r = 0.36; p = 0.478). Our multivariable model indicated that for each additional free-roaming dog estimated using GSV, the expected number of owned free-roaming dogs decreased by 2% in urban areas (p < 0.001) and increased by 2% in peri-urban areas (p = 0.004). The type of community (urban vs periurban) had an effect on the predictions, and fitting the models in periurban communities was difficult because of the sparsity of high-resolution GSV images. Using GSV imagery for estimating dog populations is a promising tool, especially in urban areas. Citizen scientists can help to generate information for disease control programs in places with insufficient resources.

Care mobilities and associated contexts of hospital-based informal caregiving in Nigeria: Towards an explanatory framework

Hospital-based informal caregiving in Nigeria is shaped by care mobilities and contextual factors such as policy contradictions and normative care philosophies. This study explores how these factors influence caregiving practices in a Nigerian tertiary health facility. Using a qualitative approach, data were gathered through interviews and observations, involving 75 participants, including 36 in-depth interviews with caregivers and inpatients, and 39 key informant interviews with staff like nurses, doctors, security guards, and ad-hoc caregivers. Findings showed that many informal caregivers traveled long distances to assist hospitalized relatives, often “hanging around” the hospital and engaging in micro-mobilities, such as running errands. Geographical distance, policy contradictions, and the financial costs of hospitalization significantly affected caregiving dynamics. Care mobilities caregivers moving within the hospital environment emerged as a critical aspect of the caregiving process. Understanding these mobilities and how they intersect with contextual factors is essential to improving caregiving experiences. The study highlights the need for policies that support informal caregivers and enhance patient outcomes, especially in terms of reducing the burdens caregivers face due to long travel distances, hospital policies, and financial challenges.

Spinal needles versus conventional needles for fine-needle aspiration biopsy of thyroid nodules—A multicenter randomized controlled trial

Objective Ultrasound-guided fine-needle aspiration biopsy (FNAB) is essential for evaluating thyroid nodules but often yields inadequate samples, leading to repeated procedures, increased discomfort, and higher costs. Previous non-randomized studies found promising results of spinal needles to improve diagnostic adequacy. Therefore, we conducted a multicenter randomized controlled trial to validate these findings. Methods Between July 1st, 2021, and April 13th, 2023, patients with suspicious thyroid nodules were randomized to receive FNAB with either a 25G spinal needle or conventional needle. The primary outcome was the rate of adequate diagnostic cytology. Secondary outcomes included procedure-related pain, sensitivity and specificity of FNAB, and adverse events. Results A total of 359 patients (75.6% female), with a mean age of 59.7 years (range 23−94) were randomized. The rate of adequate diagnostic FNAB was 86.2% (156/181) for the spinal group compared to 84.8% (151/178) for the control group (OR 1.01; 95% CI: 0.95–1.08). The mean pain scale score was 4.0 (SD = 1.8) in the spinal group and 3.9 (SD = 2.0) in the control group (p = 0.40). No complications were observed in either group. We found a significantly better cytological adequacy rate of FNABs performed by physicians with more than four years of experience in the procedure (OR=1.07; 95% CI, 1.01–1.14). Conclusions No significant improvement was found using spinal needles with a stylet compared to conventional needles. Given the significantly higher cost of spinal needles and comparable diagnostic outcomes, their routine use for thyroid FNAB is not recommended.

A long-term localization and mapping system for autonomous inspection robots in large-scale environments using 3D LiDAR sensors

Inspection mobile robots equipped with 3D LiDAR sensors are now widely used in substations and other critical circumstances. However, the application of traditional LiDAR sensors is restricted in large-scale environments. Prolonged operation poses the risk of sensor degradation, while the presence of dynamic objects disrupts the stability of the constructed map, consequently impacting the accuracy of robot localization. To address these challenges, we propose a 3D LiDAR-based long-term localization and map maintenance system, enabling autonomous deployment and operation of inspection robots. The whole system is composed of three key subsystems: a hierarchical SLAM system, a global localization system, and a map maintenance system. The SLAM subsystem includes Local Map Representation, LiDAR Odometry, Global Map Formulation and Optimization, and Dense Map Generation. Specifically, we construct an efficient map representation that voxelizes only the occupied space and computes local geometry within each voxel. The design of LiDAR Odometry ensures high consistency with this map representation mechanism. Then, to address drift errors, we formulate the global map as a graph of local submaps that undergo global optimization. Furthermore, we utilize marching cubes to generate a mesh model of the map. Our system outperforms the state-of-the-art LiDAR odometry method, LOAM, reducing average absolute position error by 30 % and 38 % on two public datasets. The comparative evaluation highlights the system’s superior accuracy and robustness, and demonstrates its high SLAM ranking in real-world scenarios. For global localization, we propose a novel ScanContext-ICP method, which integrates our improved ScanContext method, termed ScanContext++, for place recognition and global pose initialization. The Iterative Closest Point (ICP) algorithm is then employed for precise point cloud alignment and pose refinement, enabling the recovery of the robot’s position on the offline map when localization is lost. Finally, the map maintenance system tracks environmental changes, distinguishing stable features from dynamic ones. The system assigns higher weight to stable voxels, thereby improving localization accuracy. Furthermore, our time distribution mechanism refines map updates by filtering unstable points through temporal and segment-level analysis, which further enhances map maintenance. We conduct extensive experiments on public datasets to validate our system. The experimental results demonstrate that our system is effective and can be deployed on inspection mobile robots.

Optimal Anisotropic Guided Filtering in retinal fundus imaging: A dual approach to enhancement and segmentation

Retinal vascular tree segmentation and enhancement has significant medical imaging benefits because, unlike any other human organ, the retina allows non-invasive observation of blood microcirculation, making it ideal for the detection of systemic diseases. Many traditional methods of segmentation and enhancement encounter issues with visual distortion, ghost artifacts, spatially inconsistent structures, and edge information preservation as a result of the diffusion of spatial intensities at the edges. This article introduces an Optimal Anisotropic Guided Filtering (OAGF) framework tailored for retinal fundus imaging, addressing both enhancement and segmentation needs in a unified approach. The proposed methodology consists of three stages, in the first stage, we perform the illumination correction and then convert the source RGB image to YCbCr format. The luminance (Y) component is further processed through OAGF. In the second stage, optimized top-hat transform and homomorphic filtering has been performed to get segmented image. In the third stage, the enhanced image is produced by converting YCbCr to RGB format. To validate the effectiveness of the suggested approach, extensive experiments with the open-source DRIVE and STARE datasets were performed. Quantitative and qualitative assessments prove that the OAGF-enhancement and segmentation methodology surpasses current algorithms with better values in Dice Coefficient (0.860, 0.854), Precision (0.845, 0.834), and F1 Score (0.827, 0.817) on both databases.

Depression among older adults in Norway 1995–2019: Time trends, correlates, and future projections in a population study: The HUNT study

Objectives To investigate patterns and correlates of depression among Norwegian older adults (age 70+), 1995–2019, and estimate the number of older adults with depression by 2050. Design Population-based cross-sectional study Setting and participants Three surveys of the Trøndelag Health Study (Norway): HUNT2 (1995−96), HUNT3 (2007−08), and HUNT4 (2017−19). 22,822 home dwellers aged 70 + who participated in at least one of the three surveys. Methods Depression was defined as scores ≥8 on the depression subscale of the Hospital Anxiety and Depression Scale. Covariates included sex, age, education, marital status, and reported loneliness. Depression prevalence (%) was standardized to the Norwegian population by age, sex, and education for years close to the initial HUNT survey year (1995, 2006, and 2016). Projection of the total number of individuals with depression in the coming decades were estimated. Predictors of depression were analyzed with logistic regression and the potential reduction in depression prevalence by reducing the prevalence of loneliness was estimated. Results Standardized depression prevalence decreased from 16.7% (HUNT2) to 14.9% (HUNT3), and 11.5% (HUNT4), and was highest among men, the oldest (85+), the lower-educated, and in earlier surveys (all p < 0.001). Living alone was also associated with higher depression prevalence, but only if loneliness was present. While depression rates are falling, we expect the number of depressed individuals to double by 2050 as the population ages. Conclusion and implications Depression rates among adults aged 70 + decreased by 50% from 1995 to 2019, but less so among the oldest old. The rates were highest among single older men. Despite decreasing prevalence, the number of depressed older adults will increase significantly in the future. Given the major individual and societal costs of depression, this trend is alarming for societies preparing for the challenges posed by population aging. This can, however, be addressed by addressing predictors of depression.

Ageing stem cells in the knees drive arthritis damage

Predicting pulmonary function using thoracic deformity parameters in early onset scoliosis patients

Introduction Thoracospinal deformities in early onset scoliosis (EOS) patients often lead to thoracic insufficiency syndrome, in which respiration or lung growth is impaired. Pulmonary function tests (PFTs) are used to assess pulmonary deficits but are challenging to comply with for EOS patients, who typically are between 5 and 10 years old. Thus, the objective was to predict PFT values in EOS patients directly from deformity parameters measured on routine radiographs. Methods Corresponding preoperative radiographs and PFT values were retrospectively obtained from 47 EOS patients (13M/34F; mean age: 9.8 ± 3.0 years), and 19 literature-based deformity parameters were measured. Multiple linear regression (MLR) analyses using an exhaustive search feature selection method were used to estimate percent predicted forced vital capacity (%FVC) and forced expiratory volume in one second (%FEV1). Ten percent of the dataset was set aside to validate the predictive accuracy of the MLR models. Results The additive contributions of multiple thoracospinal deformity parameters successfully yielded significant (p < 0.001) MLR models that predicted %FVC (R2 = 0.54) and %FEV1 (R2 = 0.59) in EOS patients. For the validation test, no significant differences (p > 0.05) in prediction error magnitudes were found. Conclusion The developed MLR models provide the highest reported precision for predicting PFT values in EOS patients from radiographic deformity parameters. Additionally, a key subset of deformity parameters was identified, and their relative contributions to predicting PFT values provide quantitative metrics to guide surgical treatment.

“The future depends on what we do in the present” - Development positions of EU countries by levels of sustainable development and living standards

Sustainable development and standard of living of households have recently become central topics in economic analysis, scientific research, and public debate. This study aims to evaluate the positions of European Union (EU) countries and the changes occurring between 2016 and 2023 in terms of sustainable development and living standard. A hybrid multi-criteria decision-making process based on the modified positional technique for order of preference by similarity to the ideal solution (MP-TOPSIS) was employed to assess these dimensions. The research utilized data from the Eurostat database for the specified period. Both the standard of living of EU inhabitants and their countries’ levels of sustainable development were assessed. The findings revealed a clear relationship between the households’ living standards and the degree of sustainable development in EU countries. Furthermore, the analysis highlighted significant differentiation in these levels across countries, alongside a general upward trend throughout the period analyzed.

Epigenome and three-dimensional genome architecture remodeling during NDM29-mediated retro-transformation of neuroblastoma cells

Neoplastic transformation of mammalian cells involves intricate interactions between genetic, epigenetic and architecture modifications of the nucleus. Neuroblastoma is a malignant pediatric tumor with high biological and clinical heterogeneity representing a challenging model of study. We aimed to explore the changes in genome architecture and epigenetics being associated with neuroblastoma malignancy. We employed the neuroblastoma cell line SKNBE2 overexpressing the ncRNA NDM29 to differentiate from highly malignant into neuron-like cells. By 3D confocal microscopy, we explored the nuclear architecture (volume, elongation, compactness, and chromatin density). Using super-resolution microscopy (STED) and histone H3 immunolabelling we assessed the epigenetic rearrangement, and by enzyme-linked immunoassay the global DNA methylation. Then we assessed the mRNA expression of the main epigenetic modifying enzymes by quantitative PCR, and the expression of NF-κB-regulated genes by cDNA microarray. Compared to malignant NB cells, the NDM29-overexpressing cells, assuming a neuron-like phenotype, exhibited smaller and more elongated nuclei, redistribution of H3K9-acetylated and -methylated chromatin domains and DNA hypermethylation. In line with these results, in neuron-like cells the acetyltransferase KAT2A and the DNA methyltransferase DNMT1 were up-regulated, while most of NF-κB-regulated genes were down-regulated. Our findings reveal modifications of the nuclear structure and epigenome during neuroblastoma retro-transformation induced by NDM29 overexpression, with impacts on gene expression. These results offer potential insights into better understanding the mechanism of neuroblastoma malignancy in terms of chromatin rearrangements, opening exciting prospects for prognostic and therapeutic approaches with a focus on the nuclear level.