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Purpose: Abdominal incisional hernia is one of the most common complications after surgery. The preoperative evaluation of the area of abdominal wall defect and the hernia sac volume(HCV) is very important for the selection of patch size and incisional herniorrhaphy. Meanwhile the overlap range of reinforcement repair is controversial. This study aimed to explore the value of ultrasonic volume auto-scan(UVAS) in the diagnosis, classification and treatment of incisional hernia. Methods: Both the width and the area of abdominal wall defect and HCV were measured by UVAS in 50 cases with incisional hernias. In 32 of these cases, the measurements of HCV were compared with those of CT. Classification of incisional hernia based on ultrasonic images were compared with operative diagnosis. Results: The measurements of HCV by UVAS and CT 3D reconstruction had good consistency, of which the mean ratio was 1.0084. According to the location and width of abdominal wall defect, UVAS, which showed good accuracy rate (90%, 96%), reached a good agreement in the classification of incisional hernias with operative diagnoses (Kappa = 0.85, Confidence Interval [0.718,0.996]; Kappa = 0.95, Confidence Interval [0.887,0.999]). The patch area should be at least two times as large as the defect area. Conclusions: UVAS is an accurate alternative to measure the abdominal wall defect and HCV and classify the incisional hernia, with additional benefits of no radiation exposure and instant bedside interpretation. The use of UVAS is conducive to preoperative assessment of the risk of hernia recurrence and abdominal compartment syndrome.

The rapid development of tourism has caused a series of impacts on the ecosystem. Although studies on the relationship between tourism development (TD) and the ecological environment are rich, few scholars have focused on the coupling coordination between them from the perspective of ecosystem services value (ESV). Given this research gap, we evaluated the levels of TD and ESV in 78 cities of the Yellow River Basin (YRB), China based on statistical and land-use data. Then, the coupling coordination degree (CCD) model, exploratory spatial data analysis (ESDA), the spatial variogram model, and the obstacle degree model were used to analyze the spatiotemporal evolution of coupling coordination between TD and ESV and its obstacle factors. The results show the following: (1) The comprehensive TD level shows an upward trend and presents significant spatial differentiation characteristics. The total ESV of the YRB shows a fluctuating upward trend, and the average ESV presents the spatial pattern of uplift in the middle reaches. (2) The comprehensive CCD of the YRB has gradually improved, but the gap between cities has widened. The global spatial autocorrelation of CCD is significantly positive, and the spatial variability has gradually increased. An “uplift area” in southern Shaanxi always exists and has gradually expanded to Shanxi and western Henan, while eastern Henan and western Shandong become a “subsidence area”. The coupling coordination level has changed from uncoordinated to coordinated in most counties, but the problem of TD and ESV imbalance generally exists. (3) For the whole basin, TD is always the main obstacle factor at the system layer, and tourism scale and tourism economic benefit are the most significant obstacles at the category layer. At the city level, the proportion of cities where TD is the main obstacle factor exceeds 80% by 2019. Specifically, insufficient tourism scale and low tourism economic efficiency restrict the improvement of CCD in most cities. This research provides valuable references for studying the coupling coordination relationship between TU and ESV in big river basins worldwide.

AbstractHydrodynamics and socio-economic impacts of compound floods as the result of co-occurring pluvial and fluvial floods, have not been well studied, which challenges conventional urban flood risk management that treats different types of floods separately. This study generates a high-resolution land surface digital surface model based on images from unmanned aerial vehicles, and incorporates it into a combined flooding model that integrates the 1D river hydrodynamic model, 1D urban drainage hydrodynamic model and 2D overland flow model, in order to simulate the inundation characteristics of extreme floods when local pluvial floods coincide with upstream fluvial floods, and in a further step to quantify the direct economic losses on urban physical systems. As demonstrated by an empirical study of Longyan, China, the combination of pluvial and fluvial floods leads to substantial exacerbation in inundation extent and depth. Consequently, the joining of pluvial and fluvial floods greatly amplifies economic losses to urban physical systems, indicating that ignoring co-occurrence of different types of floods will potentially lead to underestimation of flood risk and insufficient adaptation. Our study emphasizes the need to account for the co-occurrence of multiple types of floods in flood risk assessment and management, to avoid the shortcomings of fragmented responses.

The Da Vinci surgical robotic system has revolutionized the field of robotic surgery and has become one of the most ubiquitous and recognized systems in the robotic surgery era. The rapid rise in China’s economy will provide crucial support for the promotion and application of robotic surgical systems in the country’s surgical field. At present, approximately 1.2 million inguinal hernia repairs are performed annually in China. However, many of these surgeries are performed via traditional open repair or laparoscopy methods. Using the purported benefits of robotic surgery system to benefit hernia patients should become a future direction for Chinese hernia surgeons.

Climate change and rapid urbanization have exacerbated the occurrence and impact of floods. It is essential to carry out a quantitative flood risk assessment and manage the flood risk before a disaster occurs. This article presents a combined riverine flood risk model to obtain the exceedance probability loss (EPL) curve and expected annual damage (EAD) under the current climate. This model includes a rapid flood model and a flood damage model. It aims to simulate the flood risk and evaluate the flood damage at 10-, 30-, 50-, 100-, and 200-year return period events. The results show that: (1) The total inundation areas will sharply increase when the flood return periods are over 30 years. (2) The EAD is 1,476 million dollars in the Jiulong River Basin (JRB). When the flood return period is over 30 years, the total damage increases sharply. (3) The flood risk in the lower reaches of the JRB is higher than in the upper reaches when the flood event is beyond a 20-year return period. (4) Industrial sector damage is the largest, followed by tertiary industry, transportation, construction, agriculture, and infrastructure. The combined model chain can quickly assess the flood risk in the river basin and judge the flood risk in a watershed compared to the national level. In addition, it can be applied to other river basins, and it will provide actionable information for future flood risk management.

The deteriorating eco-environment is the key to restrict the development of tourism urbanization in the western region. Since the eco-environmental effects caused by tourism urbanization have complex interactions, how to coordinate the relationship between the two has become one of the most severe challenges for the sustainable development of western China and even the whole of China. Previous quantitative studies on the coupling coordination between tourism urbanization and eco-environment are limited because they ignore the interactive coercion relationship between complex systems and the spatial dynamic relationship of coupling coordination. Given this research gap, this research has constructed a new comprehensive evaluation index system of tourism urbanization and eco-environment. The interactive coercion model, the coupling coordination degree model and the gravity model are used to evaluate the interaction relationship, coupling coordination type and spatial connection strength between tourism urbanization and eco-environment in western China from 2005 to 2019. The main conclusions are as follows: (1) The level of tourism urbanization shows a rapid upward trend, and the eco-environment quality shows a fluctuating and low-speed upward trend; (2) The double exponential curve between tourism urbanization and eco-environment is an inverted U-shaped curve, and the empirical analysis confirms the Kuznets hypothesis; (3) The degree of coupling coordination has experienced a development process from “seriously unbalanced” to “superior balanced”, and the interaction type has evolved into superior balanced-eco-environment lag; (4) The spatial connection of coupling coordination shows the characteristics of complication and gradient, and the interaction between provinces produces a pattern of adjacent associations. The results of this study are expected to implement an appropriate tourism urbanization development model in western China and provide decision support for the green and sustainable development of tourism urbanization and eco-environment in western China.

Abstract Background The computational prediction of methylation levels at single CpG resolution is promising to explore the methylation levels of CpGs uncovered by existing array techniques, especially for the 450 K beadchip array data with huge reserves. General prediction models concentrate on improving the overall prediction accuracy for the bulk of CpG loci while neglecting whether each locus is precisely predicted. This leads to the limited application of the prediction results, especially when performing downstream analysis with high precision requirements. Results Here we reported PretiMeth, a method for constructing precise prediction models for each single CpG locus. PretiMeth used a logistic regression algorithm to build a prediction model for each interested locus. Only one DNA methylation feature that shared the most similar methylation pattern with the CpG locus to be predicted was applied in the model. We found that PretiMeth outperformed other algorithms in the prediction accuracy, and kept robust across platforms and cell types. Furthermore, PretiMeth was applied to The Cancer Genome Atlas data (TCGA), the intensive analysis based on precise prediction results showed that several CpG loci and genes (differentially methylated between the tumor and normal samples) were worthy for further biological validation. Conclusion The precise prediction of single CpG locus is important for both methylation array data expansion and downstream analysis of prediction results. PretiMeth achieved precise modeling for each CpG locus by using only one significant feature, which also suggested that our precise prediction models could be probably used for reference in the probe set design when the DNA methylation beadchip update. PretiMeth is provided as an open source tool via https://github.com/JxTang-bioinformatics/PretiMeth .

Single-cell DNA methylation sequencing technology has brought new perspectives to investigate epigenetic heterogeneity, supporting a need for computational methods to cluster cells based on single-cell methylation profiles. Although several methods have been developed, most of them cluster cells based on single (dis)similarity measures, failing to capture complete cell heterogeneity and resulting in locally optimal solutions. Here, we present scMelody, which utilizes an enhanced consensus-based clustering model to reconstruct cell-to-cell methylation similarity patterns and identifies cell subpopulations with the leveraged information from multiple basic similarity measures. Besides, benefitted from the reconstructed cell-to-cell similarity measure, scMelody could conveniently leverage the clustering validation criteria to determine the optimal number of clusters. Assessments on distinct real datasets showed that scMelody accurately recapitulated methylation subpopulations and outperformed existing methods in terms of both cluster partitions and the number of clusters. Moreover, when benchmarking the clustering stability of scMelody on a variety of synthetic datasets, it achieved significant clustering performance gains over existing methods and robustly maintained its clustering accuracy over a wide range of number of cells, number of clusters and CpG dropout proportions. Finally, the real case studies demonstrated the capability of scMelody to assess known cell types and uncover novel cell clusters.

Electrospun nanofibrous membranes (NFM) can serve as a physical barrier, employed to confer polypropylene (PP) mesh with anti-adhesion capability for repairing abdominal wall hernias. Still, the feasibility of NFM combined with different PP meshes was poorly researched. In this study, nanofiber containing composite meshes with three PP substrates were produced by integrating the NFM barrier compositing poly (lactic-co-glycolic acid) and polycaprolactone (PLGA/PCL) into each PP mesh. Tensile mechanical test results revealed that the PP component played a dominant role in the mechanical support, and this structure has not deteriorated in any case during the process. In vitro cell studies showed that the PP mesh with a higher density was significantly beneficial for cell proliferation within 3 days of seeding, while the one with lower density exhibited notable cell proliferation after a culture of 5 days. All the meshes had excellent biocompatibility. Moreover, an intraperitoneal implantation rabbit model was used to assess the anti-adhesion effects and tissue compatibility. The results revealed that the NFM barrier could be incorporated into the lightweight PP mesh to yield the composite mesh with superior anti-adhesion property and tissue compatibility.

Rutin, a natural flavonol glycoside, is widely present in plants and foods, such as black tea and wheat tea. The antioxidant and anti-inflammatory effects of flavonoids are well known. In this study, a new electrochemical rutin sensor was developed using multiwalled carbon nanotubes/aluminum-based metal–organic frameworks (MWCNT/CAU-1) (CAU−1, a type of Al-MOF) as the electrode modification material. The suspension of multiwalled carbon tubes was dropped on the surface of the GCE electrode to make MWCNT/GCEs, and CAU−1 was then attached to the electrode surface by electrodeposition. MWCNTs and CAU−1 were characterized using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Due to the synergistic effect of CAU−1 and MWCNT-COOH, the prepared sensor showed an ultrasensitive electrochemical response to rutin. Under optimized conditions, the sensor showed a linear relationship between 1.0 × 10−9~3.0 × 10−6 M with a detection limit of 6.7 × 10−10 M (S/N = 3). The sensor also showed satisfactory stability and accuracy in the detection of real samples.

Abstract Background Determination of genome-wide DNA methylation is significant for both basic research and drug development. As a key epigenetic modification, this biochemical process can modulate gene expression to influence the cell differentiation which can possibly lead to cancer. Due to the involuted biochemical mechanism of DNA methylation, obtaining a precise prediction is a considerably tough challenge. Existing approaches have yielded good predictions, but the methods either need to combine plenty of features and prerequisites or deal with only hypermethylation and hypomethylation. Results In this paper, we propose a deep learning method for prediction of the genome-wide DNA methylation, in which the Methylation Regression is implemented by Convolutional Neural Networks (MRCNN). Through minimizing the continuous loss function, experiments show that our model is convergent and more precise than the state-of-art method (DeepCpG) according to results of the evaluation. MRCNN also achieves the discovery of de novo motifs by analysis of features from the training process. Conclusions Genome-wide DNA methylation could be evaluated based on the corresponding local DNA sequences of target CpG loci. With the autonomous learning pattern of deep learning, MRCNN enables accurate predictions of genome-wide DNA methylation status without predefined features and discovers some de novo methylation-related motifs that match known motifs by extracting sequence patterns.

The dynamic changes of nitrogen (N) loads have been significantly impacted by the rapid expansion of many cities, potentially escalating the risk of N pollution in cities. However, the spatiotemporal changes of N loads in source and sink landscapes remain unclear in urbanization. In this research, we used source–sink landscape theory to identify the source–sink landscape in the process of N flow at the city scale and investigated the spatiotemporal changes of N loads in the source–sink landscape from 2005 to 2015 in Xiamen, a rapidly urbanizing city in southern China. The total N loads of source landscapes increased by 2 times between 2005 and 2015, with an average annual growth of 26%, while the total N loads of sink landscapes climbed gradually, with an average annual increase of 8%, according to our findings. Moreover, in terms of the spatial gradient, the N loads of the source landscape fluctuated downward and reached their peak in the urban center, whereas the N loads of the sink landscape tended to rise and reached their peak outside of the city. Our findings offered a fresh viewpoint on the source–sink landscape in N flows at the city scale and offered useful guidance for N spatial management to support sustainable city development.

Rapid urbanization and climate change can cause more extensive flood risk, in the absence of urgent and efficient adaptation measures. As the occurrence of floods varies with time and space, comprehensive and dynamical assessment of the spatiotemporal variability of flood risk and understanding of its drivers is vital for flood risk management. In this study, we developed a spatial multi-criteria analysis (SMCA) framework for quantifying the spatiotemporal dynamics of flood risk through a case study in a coastal watershed of southeastern China from 1990 to 2015. A comprehensive framework for flood risk assessment was constructed from the hazard, exposure, sensitivity and adaptive capacity components with 23 indicators. The results showed that the highest risk happened in the stage of 2006–2010, while the lowest risk stage was 2011–2015, with higher flood risk in the downstream areas of Jiulong River watershed (JRW). The contribution of each indicator reflects the difference in temporal, spatial and quantity aspects. The top 5 driving factors for JRW included: peak discharge, maximum daily rainfall, age structure, wetland, and reservoir. The risk perception showed a continuous growing impact on flood risk. However, some indicators only showed obvious contributions in the specified area: for example, the built-up expansion in Zhangzhou city; the increase of dike length and the improvement of dike standard in Xinluo district; and the increase of government financial investment in Zhangping and Liancheng district. This study demonstrates the well-performance of our proposed novel approach for flood risk assessment. Our results and conclusions are also of significance for policymakers to understand and point out the deficiencies in the current actions of flood adaption, and consequently develop more targeted and spatially-specific strategies for flood adaptation, in the context of climate change and rapid urbanization.

Intensive human activity has led to dramatic land changes in coastal watersheds, which in turn cause landscape pattern changes and threaten the valuable but fragile ecosystem. This paper conducted an empirical study in Jiulong River watershed (JRW) - a coastal watershed of southeast China with a population of more than 5 million and a land area of approximately 14,700 km2, to understand the effects of land-use change on landscape pattern and ecosystem services. We characterizes and compares land-use change with the approach of Intensity Analysis, the landscape change with landscape metrics, and ecosystem services values (ESVs) change in monetary terms, between the estuary and non-estuary zones of JRW, from 1990 to 2015. The results show that the overall land-use change in the estuary zone is continuously increasing while it went down after 2000 in the non-estuary zone. The land-use change intensity is positively associated with overall landscape fragmentation and heterogeneity in the estuary zone. The built-up area has become more aggregated, while grassland, cropland and woodland have become less aggregated, which is negatively associated with the ESVs in both zones. Furthermore, the land-use change intensity was found to strongly correlate with the degradation of ESVs.

Abstract Background Lots of researches have been conducted in the selection of gene signatures that could distinguish the cancer patients from the normal. However, it is still an open question on how to extract the robust gene features. Methods In this work, a gene signature selection strategy for TCGA data was proposed by integrating the gene expression data, the methylation data and the prior knowledge about cancer biomarkers. Different from the traditional integration method, the expanded 450 K methylation data were applied instead of the original 450 K array data, and the reported biomarkers were weighted in the feature selection. Fuzzy rule based classification method and cross validation strategy were applied in the model construction for performance evaluation. Results Our selected gene features showed prediction accuracy close to 100% in the cross validation with fuzzy rule based classification model on 6 cancers from TCGA. The cross validation performance of our proposed model is similar to other integrative models or RNA-seq only model, while the prediction performance on independent data is obviously better than other 5 models. The gene signatures extracted with our fuzzy rule based integrative feature selection strategy were more robust, and had the potential to get better prediction results. Conclusion The results indicated that the integration of expanded methylation data would cover more genes, and had greater capacity to retrieve the signature genes compared with the original 450 K methylation data. Also, the integration of the reported biomarkers was a promising way to improve the performance. PTCHD3 gene was selected as a discriminating gene in 3 out of the 6 cancers, which suggested that it might play important role in the cancer risk and would be worthy for the intensive investigation.

The assessment of resilience for people, places, and systems to climate-change hazards is essential for understanding how to reduce disaster risks. Globally, a number of resilience assessment methodologies have been developed and implemented by a variety of entities, including national and local organizations, donor agencies, and academic researchers. In Bangladesh, although a number of resilience studies have been conducted, it has never been determined whether these assessments rightfully addressed conceptual understanding, methodological approaches, and disciplinary underpinnings, and maintained compliance with on-going research communications standards. To unpack this gap, we systematically reviewed 38 articles to characterize how the resilience to climate change, of coastal communities in Bangladesh, is being assessed. To operationalize the study, we have presented a brief overview of the assessment tools and then applied an analytical framework containing six criteria: comprehensiveness of dimensions, scalar relationships, temporal dynamism, addressing uncertainties of climate change by modeling and scenario-making, participatory approaches, and action plans. The overview analysis shows diverse traditions of methodological underpinnings, and reveals authors' often incomplete conceptual understandings of resilience. Results of the review analysis reveal extensive inadequacy regarding multiple dimensionality, scalar and temporal scales, and more importantly, addressing the uncertainty of climate change. In relation to comprehensiveness, current literature has failed to consistently comply with global research communication in regard to the criteria of institutional and infrastructural dimensions. More attention needs to be placed on temporal and scalar dynamics. Most importantly, the uncertainty issue is virtually overlooked in the literature, and iterative processes and the development of alternate states of planning through scenario analysis are also critical, for risk reduction and adaptation to climate-change impacts. Substantial emphasis should be given to include all possible stakeholders in the planning and implementation of any climate-change adaptation or mitigation program. Keywords: Bangladesh, Climate change, Resilience assessments, Measurement criteria, Systematic literature review

With the rapid development of cities and the increasing complexity of distribution network systems, the cableization of transmission lines and the diversification of power users have brought new challenges to the supply reliability of distribution networks. Short-time outages caused by power outages and maintenance are one of the factors that affect the reliability of the power supply in the distribution network. The non-stop load transfer through a phase-shifting transformer (PST) operation can effectively improve the reliability of power supply to complex distribution systems. Considering the operation mode and structure form and fault type of the urban distribution network in China, comparing and analyzing the applicable scenarios of different neutral grounding methods, and based on the structure and zero sequence path characteristics of PST, an improved PST-based phase shifting and grounding transformer loop closing device with low power consumption is proposed. The fault characteristics of the PST-based loop closing device under the small current grounding system are also analyzed by the sequence component method, and, finally, the effectiveness of the phase-shifting and grounding transformer device is verified by simulation under PSCAD/EMTDC for fault routing and protection configuration of the urban distribution network in China.

While land reclaimed from the sea meets the land demand for coastal development, it simultaneously causes socio-economic systems to be prone to coastal flooding induced by storm surges and sea-level rise. Current studies have seldom linked reclamation with coastal flood impact assessment, hindering the provision of accurate information to support coastal flood risk management and adaptation. This study, using Xiamen, China as a case study, incorporates the spatiotemporal dynamics of reclamation into a coastal flood impact model, in order to investigate the long-term influence of reclamation activities on coastal flood inundation and the consequent exposure of the population to coastal flooding. We find that rapid population growth, continual economic development and urbanization drive a substantial logarithmic increase in coastal reclamation. Historical and future expansions of seaward land reclamation are found to cause dramatic surges in the expected annual inundation (EAI) and the expected annual population (EAP) exposed to coastal flooding. In Xiamen, EAI is estimated to increase by 440.2% from 1947 to 2035, owing to continuing land reclamation. Consequently, the population living in the flooded area has also increased sharply: the EAP of total population is estimated to rise from 0.8% in 1947 to 4.7% in 2035, where reclamation contributes over 80% of this increase. Moreover, a future 10 cm sea-level rise in 2035 will lead to extra 5.73% and 8.15% increases in EAI and EAP, respectively, and is expected to cause massive permanent submersion in the new reclamation zone. Our findings emphasize an integration of hard structures and nature-based solutions for building resilient coasts.

Cities play a significant role in climate change mitigation and adaptation. Urban land planning shapes the urban form and is considered to be an effective approach for climate change mitigation and adaptation. Yet, there is little knowledge about what urban forms can reduce both greenhouse gas (GHG) emissions and climate stresses while considering trade-offs between them. Here, we investigate the role of urban land use in both climate change mitigation and adaptation. In particular, we assess quantitatively the competition between strategies for mitigation and adaptation and identify potential win-win solutions in land use responses. Using a coastal city as a case study, we find that the land use strategies for unilateral mitigation or adaptation can cause contradicting consequences with respect to the reductions in GHG emissions and climate stresses, i.e. reductions in GHGs could increase climate stresses or vice versa. Poorly integrated strategies potentially may compromise international efforts to meet the Climate Action in the Sustainable Development Goals. Properly integrated mitigation and adaptation strategies, or climate-sensitive land use planning, however, can lead to win-win outcomes and eventually achieve co-benefits. Yet, any co-benefits will gradually diminish if there is a delay in climate-sensitive land use planning, implying growing GHGs and intensified climate stresses. Our analysis indicates that integrating climate change mitigation and adaptation in urban land use needs to be enacted as soon as possible: any delays in implementation reduce the window to act to maximize the co-benefits. Keywords: Mitigation, Adaptation, Trade-offs, Urban land use, Coastal cities

DNA methylation is a widely investigated epigenetic mark that plays a vital role in tumorigenesis. Advancements in high-throughput assays, such as the Infinium 450K platform, provide genome-scale DNA methylation landscapes in single-CpG locus resolution, and the identification of differentially methylated loci has become an insightful approach to deepen our understanding of cancers. However, the situation with extremely unbalanced numbers of samples and loci (approximately 1:1,000) makes it rather difficult to explore differential methylation between the sick and the normal. In this article, a hybrid approach based on ensemble feature selection for identifying differentially methylated loci (HyDML) was proposed by incorporating instance perturbation and multiple function models. Experiments on data from The Cancer Genome Atlas showed that HyDML not only achieved effective DML identification, but also outperformed the single-feature selection approach in terms of classification performance and the robustness of feature selection. The intensive analysis of the DML indicated that different types of cancers have mutual patterns, and the stable DML sharing in pan-cancers is of the great potential to be biomarkers, which may strengthen the confidence of domain experts to implement biological validations.

Urban land planning shapes the urban form and is considered to be one of the many tools important for climate adaptation. Yet there is little knowledge about the adaptive capacity of urban forms to climate stress, or of an appropriate assessment method. Through a case study on the urban heat island (UHI) in Xiamen City, China, we propose a novel approach that integrates several aspects to assess the adaptive capacity of urban form to climate stress. These aspects include the calculation of urban form, the determination of climate stress and land use modeling. Our results demonstrate that this approach is applicable for assessing the adaptive capacity of urban form in the historical, current and future multitime scales. Both urban planning aspects (e.g. population density, land use mix, road density and percentage of green open space) and landscape features (e.g. shape complexity, contiguity and compactness) are found to be key urban form drivers affecting UHI. The adaptive capacity of the urban form to UHI in Xiamen City has been declining dramatically, and is expected to continue to decline in the future as long as adaptation continues to not be integrated in urban land use planning. Our analysis suggests that urban managers need to review the past development model of land use and rethink the current approach to urban planning: most urgent is the need to take full account of adaptation in future land use planning and implementation, so as to enhance climate resilience.