The unhealthy = tasty belief is associated with BMI through reduced consumption of vegetables: A cross-national and mediational analysis.

Obesity is one of the greatest public health challenges of modern times and its prevalence is increasing worldwide. With food so abundant in developed countries, many people face a conflict between desires for short-term taste and the goal of long-term health, multiple times a day. Recent research suggests that consumers often resolve these conflicts based on their lay beliefs about the healthiness and tastiness of food. Consequently, such lay beliefs can play critical roles not just in food choice but also weight gain. In this research, we show, across six countries and through mediation analysis, that adults who believe that tasty food is unhealthy (the Unhealthy = Tasty Intuition, or "UTI"; Raghunathan, Naylor, & Hoyer 2006) are less likely to consume healthy food, and thereby have a higher body mass index (BMI). In Study 1, we conducted a cross-sectional survey in five countries (Australia, Germany, Hong Kong, India, and the UK), and found that greater strength of belief in UTI was associated with higher BMI, and this relationship was mediated by lower consumption of fruits and vegetables. The observed patterns largely converged across the sampled Western and Asian-Pacific countries. In Study 2, we teased apart the mediating role of vegetable versus fruit consumption and also addressed the issue of reversed causality by predicting BMI with a measure of UTI belief taken 30 months previously. We found that vegetable consumption, but not fruit consumption, mediated the association between UTI belief and BMI. Our findings contribute to the literature by showing how lay beliefs about food can have pervasive and long-lasting effects on dietary practices and health worldwide. Implications for public policy and health practitioners are discussed.

A Self-Powered, Threshold-Based Wireless Sensor for the Detection of Floor Vibrations.

Smart buildings will soon be a reality due to innovative Internet of Things (IoT) applications. IoT applications can be employed not only for energy management in a building, but also for solving emerging social issues, such as inter-floor noise-related disputes in apartments and the solitary death of an elderly person. For example, acceleration sensors can be used to detect abnormal floor vibrations, such as large vibrations due to jumping children or unusual vibrations in a house where an elderly person is living alone. However, the installation of a conventional accelerometer can be restricted because of the sense of privacy invasion. In this study, a self-powered wireless sensor using a threshold-based method is studied for the detection of floor vibrations. Vibration levels of a bare slab in a testbed are first measured when a slab is impacted by a bang machine and an impact ball. Second, a piezoelectric energy harvester using slab vibration is manufactured to generate electrical power over a threshold. Next, the correlation among harvested energy, floor vibration, and impact noise is studied to check whether harvested energy can be employed as a condition detection threshold. Finally, a prototype of a self-powered wireless sensor to detect abnormal conditions in floor vibrations is developed and its applicability is demonstrated.

Decreased expression of SOX7 induces cell proliferation and invasion and correlates with poor prognosis in oral squamous cell carcinoma.

BACKGROUND: SOX7, a member of the SOX family of transcription factors, acts as a tumor suppressor in multiple cancers. Downregulation of SOX7 has been reported in advanced tumors and correlates with poor prognosis. The aims of this study were to investigate the effects of SOX7 on cell proliferation, invasion, and colony formation in oral squamous cell carcinoma (OSCC) cells and to evaluate the effectiveness of SOX7 protein as a prognostic indicator for OSCC patients. METHODS: oral squamous cell carcinoma (OSCC) cell lines were treated with SOX7 small interfering RNA or SOX7 peptide, and their effects on cell proliferation, invasiveness, and colony formation were investigated by proliferation, in vitro invasion, and clonogenic assays. SOX7 protein expression in OSCC and normal oral mucosal tissues was examined by immunohistochemistry. Associations between SOX7 protein expression and clinicopathological parameters of OSCC patients were statistically analyzed. RESULTS: SOX7 silencing-induced cell proliferation and invasion in SCC-4 cells. SOX7 peptide treatment inhibited cell proliferation, colony formation, and invasion in SCC-9 and SCC-25 cells. Expression of SOX7 protein was decreased in OSCC tissues compared with normal oral mucosal tissues (P<.001). Negative SOX7 expression in patients with OSCC was significantly associated with positive lymph node metastasis (P=.041), advanced TNM stage (P=.024), and poor prognosis (P=.017). CONCLUSIONS: These results suggest that SOX7 inhibits cell proliferation, colony formation, and invasion in OSCC as a tumor suppressor and that negative SOX7 expression could be a poor prognostic indicator for patients with OSCC.

Differential Progression of Midbrain Atrophy in Parkinsonism: Longitudinal MRI Study.

AIMS: To elucidate different patterns of progression of midbrain atrophy in patients with Richardson's syndrome (RS), progressive supranuclear palsy-parkinsonism (PSP-P), and Parkinson's disease (PD) using magnetic resonance imaging (MRI)-based visual rating indexes. METHODS: We recruited 12 patients with PSP-RS, 12 with PSP-P, and 23 with PD for whom MRIs had been followed up for at least 2 years (mean ± SD, 4.9 ± 1.6 years) after the initial MRI. MRI-based visual rating indexes were used to estimate midbrain atrophy, including the ratio of the pontine to midbrain tegmental areas (P/M ratio) on a midsagittal image, the length between the interpeduncular fossa and the center of the cerebral aqueduct at the midmammillary-body level (MTEGM) on axial images, and the morning glory sign. RESULTS: Initially, there were no differences in MRI-based visual rating indexes between PSP-P and PD, while PSP-RS showed a higher P/M ratio and lower MTEGM compared with PSP-P and PD. In PD, the P/M ratio and MTEGM remained stable with disease progression. However, the extent of changes between initial and follow-up indexes was similarly greater for both PSP-RS and PSP-P than for PD. Finally, PSP-P showed a higher P/M ratio and lower MTEGM compared with PD in the follow-up, while PSP-RS still exhibited the most profound changes. CONCLUSIONS: Midbrain atrophy progresses differentially in patients with PSP-RS, PSP-P, and PD. Longitudinal measurements of midbrain atrophy using MRI-based visual rating indexes can help distinguish patients with PSP-P from those with PSP-RS and PD.

More Similar but Less Satisfying: Comparing Preferences for and the Efficacy of Within- and Cross-Category Substitutes for Food.

When people cannot get what they want, they often satisfy their desire by consuming a substitute. Substitutes can originate from within the taxonomic category of the desired stimulus (i.e., within-category substitutes) or from a different taxonomic category that serves the same basic goal (i.e., cross-category substitutes). Both a store-brand chocolate (within-category substitute) and a granola bar (cross-category substitute), for example, can serve as substitutes for gourmet chocolate. Here, we found that people believe that within-category substitutes, which are more similar to desired stimuli, will more effectively satisfy their cravings than will cross-category substitutes (Experiments 1, 2a, and 2b). However, because within-category substitutes are more similar than cross-category substitutes to desired stimuli, they are more likely to evoke an unanticipated negative contrast effect. As a result, unless substitutes are equivalent in quality to the desired stimulus, cross-category substitutes more effectively satisfy cravings for the desired stimulus (Experiments 3 and 4).

Atrophy of the Cerebellar Vermis in Essential Tremor: Segmental Volumetric MRI Analysis.

Postmortem studies of essential tremor (ET) have demonstrated the presence of degenerative changes in the cerebellum, and imaging studies have examined related structural changes in the brain. However, their results have not been completely consistent and the number of imaging studies has been limited. We aimed to study cerebellar involvement in ET using MRI segmental volumetric analysis. In addition, a unique feature of this study was that we stratified ET patients into subtypes based on the clinical presence of cerebellar signs and compared their MRI findings. Thirty-nine ET patients and 36 normal healthy controls, matched for age and sex, were enrolled. Cerebellar signs in ET patients were assessed using the clinical tremor rating scale and International Cooperative Ataxia Rating Scale. ET patients were divided into two groups: patients with cerebellar signs (cerebellar-ET) and those without (classic-ET). MRI volumetry was performed using CIVET pipeline software. Data on whole and segmented cerebellar volumes were analyzed using SPSS. While there was a trend for whole cerebellar volume to decrease from controls to classic-ET to cerebellar-ET, this trend was not significant. The volume of several contiguous segments of the cerebellar vermis was reduced in ET patients versus controls. Furthermore, these vermis volumes were reduced in the cerebellar-ET group versus the classic-ET group. The volume of several adjacent segments of the cerebellar vermis was reduced in ET. This effect was more evident in ET patients with clinical signs of cerebellar dysfunction. The presence of tissue atrophy suggests that ET might be a neurodegenerative disease.

Vestibular Performance During High-Acceleration Stimuli Correlates with Clinical Decline in SCA6.

In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33-72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=-0.927, p<0.001). Selective decrease of the vestibular responses during high-acceleration, high-frequency stimuli may be ascribed to degeneration of either the flocculus or vestibular nuclei. The performance of the VOR during high-acceleration, high-frequency head impulses may be a quantitative indicator of clinical decline in SCA6.

Positional suppression of periodic alternating nystagmus.

A 43-year-old man with a high-grade glioma involving the cerebellar nodulus showed a near-complete suppression of periodic alternating nystagmus (PAN) in the lateral decubitus position to either side. This positional modulation of PAN is consistent with suppression of the velocity storage mechanism by head position changes (tilt dumping) and is supportive of the role of the velocity storage mechanism in generating PAN.

Exploring causal effects of sarcopenia on risk and progression of Parkinson disease by Mendelian randomization.

Previous observational studies suggested that sarcopenia is associated with Parkinson disease (PD), but it is unclear whether this association is causal. The objective of this study was to examine causal associations between sarcopenia-related traits and the risk or progression of PD using a Mendelian randomization (MR) approach. Two-sample bidirectional MR analyses were conducted to evaluate causal relationships. Genome-wide association study (GWAS) summary statistics for sarcopenia-related traits, including right handgrip strength (n = 461,089), left handgrip strength (n = 461,026), and appendicular lean mass (n = 450,243), were retrieved from the IEU OpenGWAS database. GWAS data for the risk of PD were derived from the FinnGen database (4235 cases; 373,042 controls). Summary-level data for progression of PD, including progression to Hoehn and Yahr stage 3, progression to dementia, and development of levodopa-induced dyskinesia, were obtained from a recent GWAS publication on progression of PD in 4093 patients from 12 longitudinal cohorts. Significant causal associations identified in MR analysis were verified through a polygenic score (PGS)-based approach and pathway enrichment analysis using genotype data from the Parkinson's Progression Markers Initiative. MR results supported a significant causal influence of right handgrip strength (odds ratio [OR] = 0.152, 95% confidence interval [CI] = 0.055-0.423, adjusted P = 0.0036) and appendicular lean mass (OR = 0.597, 95% CI = 0.440-0.810, adjusted P = 0.0111) on development of levodopa-induced dyskinesia. In Cox proportional hazard analysis, higher PGSs for right handgrip strength (hazard ratio [HR] = 0.225, 95% CI = 0.095-0.530, adjusted P = 0.0019) and left handgrip strength (HR = 0.303, 95% CI = 0.121-0.59, adjusted P = 0.0323) were significantly associated with a lower risk of developing levodopa-induced dyskinesia, after adjusting for covariates. Pathway enrichment analysis revealed that genome-wide significant single-nucleotide polymorphisms for right handgrip strength were substantially enriched in biological pathways involved in the control of synaptic plasticity. This study provides genetic evidence of the protective role of handgrip strength or appendicular lean mass on the development of levodopa-induced dyskinesia in PD. Sarcopenia-related traits can be promising prognostic markers for levodopa-induced dyskinesia and potential therapeutic targets for preventing levodopa-induced dyskinesia in patients with PD.

What Makes Deviant Places?

Urban safety plays an essential role in the quality of citizens' lives and in the sustainable development of cities. In recent years, researchers have attempted to apply machine learning techniques to identify the role of location-specific attributes in the development of urban safety. However, existing studies have mainly relied on limited images (e.g., map images, single- or four-directional images) of areas based on a relatively large geographical unit and have narrowly focused on severe crime rates, which limits their predictive performance and implications for urban safety. In this work, we propose a novel method that predicts "deviance," which includes formal deviant crimes (e.g., murders) and informal deviant behaviors (e.g., loud parties at night). To do this, we first collect a large-scale geo-tagged dataset consisting of incident report data for seven metropolitan cities, along with corresponding sequential images around incident sites obtained from Google Street View. We then design a convolutional neural network that learns spatio-temporal visual attributes of deviant streets. Experimental results show that our framework is able to reliably recognize real-world deviance in various cities. Furthermore, we analyze which visual attribute is important for deviance identification and severity estimation with respect to social science as well as activated feature maps in the neural network.

Head-shaking aids in the diagnosis of acute audiovestibular loss due to anterior inferior cerebellar artery infarction.

OBJECTIVE: To determine the patterns and diagnostic value of head-shaking nystagmus (HSN) in patients with acute audiovestibular loss. METHOD: Eighteen patients underwent evaluation of spontaneous nystagmus, gaze-evoked nystagmus, HSN, head impulse test, ocular tilt reaction, subjective visual vertical, bithermal caloric tests, and pure-tone audiogram. The findings were compared with those of 21 patients with labyrinthitis. RESULTS: Fifteen patients (83%) exhibited HSN, and the horizontal HSN usually beat contralesionally (10/14, 71%). However, 9 (50%) patients also showed patterns of central HSN that included perverted HSN (n=7), HSN in the opposite direction of spontaneous nystagmus (n=4), and HSN beating towards unilateral canal paresis or abnormal head impulse testing (n=3). Overall, central HSN, gaze-evoked nystagmus, and normal head impulse testing were specific for anterior inferior cerebellar artery (AICA) infarction. Moreover, central HSN was the only sign that indicated stroke in 1 of our patients with isolated audiovestibular syndrome. Lesion subtraction analyses revealed that damage to the flocculus was relatively frequent in patients with perverted HSN. CONCLUSIONS: In AICA infarction, HSN was common with both peripheral and central patterns. Careful evaluation of HSN may provide clues for AICA infarction in patients with acute audiovestibular loss.

Inducing consumers to use calorie information: a multinational investigation.

OBJECTIVE: We identify individuals who set daily intake budgets and examine if an intervention making people estimate their calorie intake up to a certain point in the day helps those setting daily budgets to regulate their calorie intake for the remainder of the day, after high prior consumption. DESIGN: We conducted an online experiment in five countries: Australia, China, Germany, India, and the UK (n = 3,032) using a 2 (setting calorie budget: yes vs. no, measured) x 2 (intervention: intake reminder vs. control, manipulated) between-subjects design, with the amount of prior consumption measured. Participants were contacted in the afternoon. Those in the intervention condition were asked to estimate their prior calorie intake on that day. MAIN OUTCOME MEASURES: We measured the individual characteristics of those who set daily calorie budgets and the intended calorie intake for the remainder of the day. RESULTS: Among people who set daily calorie budgets, the intervention reduced intended calorie intake for the remainder of the day by 176 calories if they had already consumed a high amount of calories that day. CONCLUSION: A timely intervention to estimate one's calorie intake can lower additional intended calorie intake among those who set daily calorie budget.

GBA1 Variants and Parkinson's Disease: Paving the Way for Targeted Therapy.

Glucosylceramidase beta 1 (GBA1) variants have attracted enormous attention as the most promising and important genetic candidates for precision medicine in Parkinson's disease (PD). A substantial correlation between GBA1 genotypes and PD phenotypes could inform the prediction of disease progression and promote the development of a preventive intervention for individuals at a higher risk of a worse disease prognosis. Moreover, the GBA1-regulated pathway provides new perspectives on the pathogenesis of PD, such as dysregulated sphingolipid metabolism, impaired protein quality control, and disrupted endoplasmic reticulum-Golgi trafficking. These perspectives have led to the development of novel disease-modifying therapies for PD targeting the GBA1-regulated pathway by repositioning treatment strategies for Gaucher's disease. This review summarizes the current hypotheses on a mechanistic link between GBA1 variants and PD and possible therapeutic options for modulating GBA1-regulated pathways in PD patients.

Patterns of spontaneous and head-shaking nystagmus in cerebellar infarction: imaging correlations.

Horizontal head-shaking may induce nystagmus in peripheral as well as central vestibular lesions. While the patterns and mechanism of head-shaking nystagmus are well established in peripheral vestibulopathy, they require further exploration in central vestibular disorders. To define the characteristics and mechanism of head-shaking nystagmus in central vestibulopathies, we investigated spontaneous nystagmus and head-shaking nystagmus in 72 patients with isolated cerebellar infarction. Spontaneous nystagmus was observed in 28 (39%) patients, and was mostly ipsilesional when observed in unilateral infarction (15/18, 83%). Head-shaking nystagmus developed in 37 (51%) patients, and the horizontal component of head-shaking nystagmus was uniformly ipsilesional when induced in patients with unilateral infarction. Perverted head-shaking nystagmus occurred in 23 (23/37, 62%) patients and was mostly downbeat (22/23, 96%). Lesion subtraction analyses revealed that damage to the uvula, nodulus and inferior tonsil was mostly responsible for generation of head-shaking nystagmus in patients with unilateral posterior inferior cerebellar artery infarction. Ipsilesional head-shaking nystagmus in patients with unilateral cerebellar infarction may be explained by unilateral disruption of uvulonodular inhibition over the velocity storage. Perverted (downbeat) head-shaking nystagmus may be ascribed to impaired control over the spatial orientation of the angular vestibulo-ocular reflex due to uvulonodular lesions or a build-up of vertical vestibular asymmetry favouring upward bias due to lesions involving the inferior tonsil.

Physeal growth arrest after tibial lengthening in achondroplasia: 23 children followed to skeletal maturity.

BACKGROUND AND PURPOSE: Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with achondroplasia. METHODS: We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. RESULTS: Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. INTERPRETATION: Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence-especially when lengthening of more than 50% is attempted.

Trehalose ameliorates prodromal non-motor deficits and aberrant protein accumulation in a rotenone-induced mouse model of Parkinson's disease.

Trehalose has been recently revealed as an attractive candidate to prevent and modify Parkinson's disease (PD) progression by regulating autophagy; however, studies have only focused on the reduction of motor symptoms rather than the modulation of disease course from prodromal stage. This study aimed to evaluate whether trehalose has a disease-modifying effect at the prodromal stage before the onset of a motor deficit in 8-week-old male C57BL/6 mice exposed to rotenone. We found significant decrease in tyrosine hydroxylase immunoreactivity in the substantia nigra and motor dysfunction after 2 weeks rotenone treatment. Mice exposed to rotenone for a week showed an accumulation of protein aggregates in the brain and prodromal non-motor deficits, such as depression and olfactory dysfunction, prior to motor deficits. Trehalose significantly improved olfactory dysfunction and depressive-like behaviors and markedly reduced α-synuclein and p62 deposition in the brain. Trehalose further ameliorated motor impairment and loss of nigral tyrosine hydroxylase-positive cells in rotenone-treated mice. We demonstrated that prodromal non-motor signs in a rotenone-induced PD mouse model are associated with protein aggregate accumulation in the brain and that an autophagy inducer could be valuable to prevent PD progression from prodromal stage by regulating abnormal protein accumulation.

The perspectives of users and developers in designing and developing O-arm imaging system.

A questionnaire survey was performed to investigate the different knowledge of radiation exposure, awareness and expectation for O-arm imaging system between the users (orthopaedic surgeons) and the developers (engineers). A total of 93 orthopaedic surgeons and 19 engineers participated and answered the questionnaire consisting of 18 items designed for this study. The items were focused on knowlege, awareness, and expectation. Orthopaedic surgeons had higher scores for items of knowledge domains regarding radiation exposure than the engineers while the engineers were more sensitive to radiation hazards and adopted higher levels of radiation protection than orthopaedic surgeons in the awareness domain. Most engineers and orthopaedic surgeons answered that the requirements of diagnostic and intraoperative imaging systems differ. Image resolution, a low radiation exposure, and the time required for image acquisition was the top three requirements of O-arm selected by engineers. On the other hand, the top three requirements according to orthopaedic surgeons were; image resolution, expediency, and spatial occupancy. User requirements need to be reflected in developing O-arm along with basic requirements such as image resolution and low radiation exposure.

Deep intramedullary infection in tibial lengthening over an intramedullary nail.

Tibial lengthening over an intramedullary (IM) device is associated with a risk of deep intramedullary infection; there is so far no guideline for decision making between early removal and delayed removal of the nail. Tibial lengthening over an intramedullary nail/Rush pin was performed in 118 limb segments (63 patients) from 2004 to 2008 in our institution. Fifty five patients had bilateral tibial lengthening. Ninety nine of the 118 segments went on to healing without infection, while 13 segments developed superficial infection and 6 segments developed deep infection. Among 6 patients with deep infection, 4 patients underwent early removal of the nail when deep infection signs and symptoms occurred and 2 patients underwent delayed removal of the nail at 11 months. The 6 segments with deep infection differed significantly with respect t to the callus pattern (p < 0.05) and density (p = 0.0001) from those without infection and with superficial infection. In this small sugroup, removal of the nail was delayed in two patients as there was visible callus bridging at more than one cortex, and deep infection subsided after local drainage.

Bis(2-phenyl-ethyl-ammonium) tetra-chloridocobaltate(II).

Crystals of the title compound, (C(6)H(5)CH(2)CH(2)NH(3))(2)[CoCl(4)], were grown by the solvent-evaporation method. This inorganic-organic hybrid compound exhibits a layered structure in which isolated CoCl(4) inorganic layers alternate with bilayers of phenylethylammonium cations. Although the inorganic anion is zero-dimensional, the layered structure is stabilized via N-H⋯Cl hydrogen bonds. The CoCl(4) tetra-hedra connect to the cations through N-H⋯Cl hydrogen bonds, building a two-dimensional network extending parallel to (010).

Informed indulgence: the effects of nutrition information provision and dietary restraint on consecutive food consumption decisions.

OBJECTIVE: Nutrition and menu labelling have been increasingly implemented worldwide. This research examines the effect of nutrition information provision on the immediate and subsequent consumption decisions of restrained and unrestrained eaters. DESIGN: We conducted three scenario-based experiments. In Study 1 (N = 478) and Study 2 (N = 199), we manipulated the availability of nutrition information and measured dietary restraint. Study 3 (N = 275) extended Study 2 by adding a condition where we provided reference information about recommended daily calories. MAIN OUTCOME MEASURES: We measured choices between relatively low-calorie and high-calorie alternatives (Studies 1-3) and measured a subsequent decision to consume indulgent food (Studies 2 and 3). RESULTS: Nutrition information did not generally affect choices between low-calorie and high-calorie options, irrespective of dietary restraint. However, restrained eaters who chose a high-calorie option in the presence of nutrition information indicated they would reduce subsequent intake. CONCLUSION: Nutrition information does not necessarily reduce the choice of relatively high-calorie food, but it can help restrained eaters reduce subsequent intake after a high-calorie choice. These results suggest that despite not having an immediate effect on choices, nutrition and menu labelling may benefit restrained eaters at a later time.