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Objective Unidentified mechanisms largely restrict the viability of effective therapies in pharmacoresistant epilepsy. Our previous study revealed that hyperactivity of the subiculum is crucial for the genesis of pharmacoresistance in temporal lobe epilepsy (TLE), but the underlying molecular mechanism is not clear. Methods Here, we examined the role of subicular caspase-1, a key neural pro-inflammatory enzyme, in pharmacoresistant TLE. Results We found that the expression of activated caspase-1 in the subiculum, but not the CA1, was upregulated in pharmacoresistant amygdaloid-kindled rats. Early overexpression of caspase-1 in the subiculum was sufficient to induce pharmacoresistant TLE in rats, whereas genetic ablation of caspase-1 interfered with the genesis of pharmacoresistant TLE in both kindled rats and kainic acid-treated mice. The pro-pharmacoresistance effect of subicular caspase-1 was mediated by its downstream inflammasome-dependent interleukin-1β. Further electrophysiological results showed that inhibiting caspase-1 decreased the excitability of subicular pyramidal neurons through influencing the excitation/inhibition balance of presynaptic input. Importantly, a small molecular caspase-1 inhibitor CZL80 attenuated seizures in pharmacoresistant TLE models, and decreased the neuronal excitability in the brain slices obtained from patients with pharmacoresistant TLE. Interpretation These results support the subicular caspase-1-interleukin-1β inflammatory pathway as a novel alternative mechanism hypothesis for pharmacoresistant TLE, and present caspase-1 as a potential target. ANN NEUROL 2021;90:377-390.

Children (n = 240) between the ages of 2 and 17 years were randomly selected from three cities in China. The total amount of soil and dust (SD) on their hands was measured and ranged from 3.50–187.39 mg (median = 19.49 mg). We screened for seven elements (Ce, V, Y, Al, Ba, Sc, and Mn), and Ce levels were used to calculate hand SD by variability and soil elements. The main factors affecting SD amount were location and age group, as identified using a conditional inference tree. Hand SD and the hand SD intake rate were highest in Gansu Province, followed by Guangdong and Hubei provinces, respectively. Hand SD and the hand SD intake rate were highest among children in primary school, followed by kindergarten and secondary school, respectively. The hand SD intake rate of the three typical areas was 11.9 mg/d, which was about 26.6% of the children’s soil intake rate (44.8 mg/d), indicating that hand-to-mouth contact is not the main route for children’s soil intake in the three areas of China.

Aims Noninvasive music adjuvant therapy shows great potential in improving seizure control when combined with routine antiepileptic drugs. However, the diversity of previous music protocols has resulted in disparate outcomes. The optimized protocol and features for music adjuvant therapy are still not fully understood which limits its feasibility. Methods By applying different regimens of music therapy in various temporal lobe epilepsy models, we evaluated the effect of music in combination with sub‐dose drugs on epileptic seizures to determine the optimized protocol. Results A subgroup of kindled mice that were responsive to music adjuvant therapy was screened. In those mice, sub‐dose drugs which were noneffective on kindled seizures, alleviated seizure severity after 12 h/day Mozart K.448 for 14 days. Shorter durations of music therapy (2 and 6 h/day) were ineffective. Furthermore, only full‐length Mozart K.448, not its episodes or other music varieties, was capable of enhancing the efficacy of sub‐dose drugs. This music therapeutic effect was not due to increasing cerebral drug concentration, but instead was related with the modulation of seizure electroencephalogram (EEG) spectral powers in the hippocampus. Conclusion These results indicate that long‐term full‐length Mozart K.448 could enhance the anti‐seizure efficacy of sub‐dose drugs and may be a promising noninvasive adjuvant therapy for temporal lobe epilepsy., Music adjuvant therapy promotes the efficacy of sub‐dose antiepileptic drugs in both hippocampal and amygdaloid kindled temporal lobe epileptic mice. Listening to full‐length Mozart K.448 for 12 h/day is the optimal protocol for music adjuvant therapy.

Virtual Reality (VR) has been around for a long time but has come into the spotlight only recently. From an industrial perspective, this article serves as a proverbial scalpel to dissect the different use cases and commercial applications of VR in Singapore. Before researching the Singapore market, we examine how VR has evolved. At the moment, the global annual budget for VR (and augmented reality) is at an upward trend with a leading growth in market value for the training sector. VR in Singapore has also seen a rapid development in recent years. We discuss some of the Singapore government's initiatives to promote the commercial adoption of VR for the digital economy of the nation. To address the mass adoption of VR, we present VRcollab's business solutions for the construction and building industry. 2020 is one of the most important years for VR in history.

Based on 1186 published studies, the first national-scale assessment of cadmium (Cd) contamination in agricultural soils across China was conducted. Cd concentrations, temporal and spatial variations, and ecological and health risks resulted from Cd exposure were analyzed. A small part of sampling sites with Cd concentration surpass the screening value and the control value (GB15618-2018), respectively. Soil Cd concentrations in South China were higher than other regions. Ecological risks resulting from Cd contamination were low. Soil Cd concentrations accumulated gradually from 1981 to 2016. Cd mainly came from anthropogenic activities, such as mining, smelting, sewage irrigation, and fertilization. Linear correlations were observed between application amounts of fertilizers and Cd concentrations in soil, indicating that the application of nitrogen, phosphorus, potassium, and compound fertilizers is an important contributor of Cd in soils. This study details the overall Cd contamination status of agricultural soils in China, thus can provide insights for policymakers regarding contamination prevention measures.

PurposeFollowing positive results of Lean implementation in manufacturing environments, Lean has become an emerging philosophy for clients and suppliers of information technology (IT) services. However, how to implement Lean in IT outsourcing relationships has been addressed sparsely in academic literature. The purpose of this paper is to investigate critical success factors (CSFs) for implementing Lean in IT outsourcing relationships. Key findings, implications and avenues for future research are discussed.Design/methodology/approachSix IT outsourcing relationships were qualitatively investigated by means of 36 semi-structured interviews. CSFs were identified based on interview transcription analyses, selection techniques and expert reviews.FindingsIn total, 16 CSFs for Lean implementation in IT outsourcing relationships are identified and described.Practical implicationsThe CSFs presented in this paper indicate key areas that deserve managerial attention to steer Lean implementation efforts in IT outsourcing relationships in a favorable direction.Originality/valueThis study is the first to describe the phenomenon of “Lean IT outsourcing” and provides researchers and practitioners with a foundation to further examine Lean implementation in IT outsourcing relationships.

Companies increasingly tender knowledge-intensive tasks using crowdsourcing platforms to gain access to scarce knowledge and skills otherwise out of reach, and in this way, gaining competitive advantage. Despite its potential, existing crowdsourcing platforms encounter several challenges, including (1) fragmentation of expertise, as there are many platforms, (2) distrust between task providers and crowdsourcing participants, as identity and past performance are often not known, and (3) inability to learn from experience due to a lack of openness. A reference architecture for blockchain-based knowledge-intensive crowdsourcing platforms to mediate transactions between demand and supply of knowledge is designed in this paper to overcome these challenges. A design science research method is followed to develop the architecture. The reference architecture shows how blockchain and smart contract components can be integrated to support and coordinate knowledge-intensive crowdsourcing activities. By removing traditional e-commerce intermediaries, blockchain reduces search friction, knowledge transfer costs, and cheating by task providers or crowdsourcing participants.

It is important to understand the status and extent of soil contamination with heavy metals to make sustainable management strategies for agricultural soils. Input and output inventory of heavy metals in agricultural soil of Zhejiang Province was systematically studied. The results showed that atmospheric deposition was responsible for 47.88% and 76.87% of the total Cr and Pb inputs, respectively. Livestock manures accounted for approximately 54–85% of the total As, Cu, and Zn inputs. Livestock manure and irrigation were the main sources of Hg, contributed 50.25% and 38.63% of the total inputs, respectively. Ni was derived mainly from atmospheric deposition (57.86%), followed by irrigation (22.69%). As for Cd, the relative contributions of atmospheric deposition, irrigation, and livestock manure were similar. Crop harvesting and leaching were found to be the dominant output pathways of the soil elements Cd, Cu, Hg, and Zn, being responsible for 74.43–83.62% of the total outputs. Surface runoff was the dominant output pathway for As, Cr, Ni, and Pb, accounting for approximately 73.36%, 46.32%, 54.16%, and 48.11% of the total outputs, respectively. According to prediction and early warning, Cd is the priority control pollutant in agricultural soil. This work will assist in developing strategies for reducing heavy metal inputs to agricultural soil and effectively targeting policies to protect soil environment from long-term heavy metal accumulation.

Epilepsy, one of the most severe neurological diseases, is characterized by abrupt recurrent seizures. Despite great progress in the development of antiseizure drugs (ASDs) based on diverse molecular targets, more than one third of epilepsy patients still show resistance to ASDs, a condition termed pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy involves serious challenges. In the past decade, promising advances have been made in the use of interdisciplinary techniques involving biophysics, bioinformatics, biomaterials and biochemistry, which allow more precise prognosis and development of drug target for pharmacoresistant epilepsy. Notably, novel experimental tools such as viral vector gene delivery, optogenetics and chemogenetics have provided a framework for promising approaches to the precise treatment of pharmacoresistant epilepsy. In this review, historical achievements especially recent advances of the past decade in the prognosis and treatment of pharmacoresistant epilepsy from both clinical and laboratory settings are presented and summarized. We propose that the further development of novel experimental tools at cellular or molecular levels with both temporal and spatial precision are necessary to make improve the management and drug development for pharmacoresistant epilepsy in the clinical arena.

Knowledge management (KM) in information technology outsourcing (ITO) is important to the organizations which pursue long-term strategic benefits and innovation. Effective KM mechanism in outsourcing enables both parties to continuously exchange knowledge and promotes collective learning. This paper investigates the role of Lean principles in supporting KM in ITO relationships. Drawn from the knowledge-based view of the firm, knowledge accessing and knowledge integration and utilization are identified as two key KM processes in outsourcing. Three case studies conducted in different service industries with 18 interviews indicate that the two KM processes were supported by four Lean principles: respect for people, continuous improvement, systems thinking, and proactive behavior. Those principles can be implemented with different tools at different organizational levels. This study reveals the relevance between Lean and KM in ITO relationships, which has not been reported by the KM literature. It also provides implications to ITO practitioners for the implementation of Lean principles.

Organizations are attempting to harness the power of big data analytics. Enterprise architecture can be used as an instrument to integrate big data analytics into the existing IT landscape and enabling the development of capabilities to create value from these technologies. Yet, there is limited research about the role of enterprise architecture in adopting big data analytics. This paper explores enterprise architecture roles and capabilities for the adoption of big data analytics by conducting a qualitative case study at the Dutch Tax and Customs Administration. The first attempt to adopt big data analytics was focused on integrating analytics into the current complex IT landscape, but this encountered many challenges and resulted in slow progress. To overcome these challenges, a separate department was created to quickly harness the potential of big data analytics. Enterprise architecture was used for impact analysis and to create a transition process. The findings suggest that enterprise architecture was used in different ways at the various stages of adoption and implementation, requiring different roles and a different set of capabilities. Enterprise architecture was found to be contingent on the type of technology and the situation at hand. We recommend more research into the role of the context in enterprise architecture research.

Mercury exchange between soil and air is an important processe governing the biogeochemical cycling of Hg. This study investigated the in situ soil-air Hg fluxes in agricultural soils of Quzhou, Zhejiang Province, China, using a dynamic flux chamber coupled with a Hg vapor analyzer. Soil-air Hg exchange fluxes were overall emission for all seasons, indicating that agricultural soil was a Hg source for the atmosphere. Seasonal variations in soil-air Hg flux were observed, with low values in winter, elevated values in spring, peak values in summer, and a decline in autumn. Mercury emissions from soils showed a clear diurnal pattern where Hg released into the atmosphere reached a maximum at 11 a.m. and declined to a minimum at 2:00 and 20:00 in spring and summer, respectively. Meanwhile, soil-air Hg flux peaked at 1 p.m. and declined to a minimum at 6:00 and 23:00 in autumn and winter, respectively. The impact of each factor on the Hg exchange between soil and air varied in different seasons. Soil temperature was the major variable controlling the Hg flux in winter and spring; soil temperature and total gaseous Hg evidently affected the Hg flux in summer, and ozone (O3) played a dominant role in influencing the Hg flux in autumn. Models for estimating the Hg evasive flux from soils were developed, and the atmospheric O3 concentration was used for the first time as a parameter in these models. The measured and modeled Hg fluxes showed significant linear correlations (R2 = 0.61; P

Urban parks are an important part of the urban ecological environment. The environmental quality of parks is related to human health. To evaluate sources of polycyclic aromatic hydrocarbons (PAHs) in soils of urban parks and their possible health risks, soil samples from 122 parks in Beijing, China, were collected and analyzed. The total content of 16 PAHs between 0.066 and 6.867 mg/kg. Four-ring PAHs were predominant, followed by 5-ring PAHs, while the fraction of 2-ring PAHs was the lowest. The dominant PAHs sources were found to be coal combustion and oil fuels such as gasoline and diesel. A conditional inference tree (CIT) was used to identify the key influencing factors for PAHs. Traffic emissions was the most important factor, followed by coal consumption, as well as the history and location of the park. Incremental lifetime cancer risk (ILCR) for urban park soil in Beijing were low under normal conditions. The soil PAHs exposure pathway risk for both children and adults decreased in the following order: ingestion > dermal contact > inhalation. The risk from soil in parks to children’s health is slightly higher than that of adults, although the health risk due to exposure to PAHs was not extraordinary. Ecosystem risk was negligible.

Based on 1677 published studies, 1648 sites across China collected from 1985 to 2016 were used to research the concentrations of arsenic in agricultural soils. In order to understand the status of arsenic pollution in agricultural soils in China over the past three decades, and to learn about the arsenic stocks in agricultural soils in various regions, and compared the relationship with annual arsenic emissions in China, and finally evaluated the potential ecological risks and human health risks. The median arsenic concentration in the surface agricultural soils of China was 10.40 mg Kg−1, and it ranged from 0.4 mg Kg−1 to 175.8 mg Kg−1. The inventory of arsenic in Chinese agricultural surface soils was estimated to be 3.71 × 106 t. In this study, the arsenic concentrations were found to be higher in Central, South, and Southwest China than those in other regions. The trend of arsenic pollution in agricultural soils has gradually increased over the past three decades. However, the growth rate of arsenic concentrations pollution in farmlands agricultural in China slowed during 2012–2016. The ecological risk index and geoaccumulation index revealed that arsenic in Chinese agricultural soil poses a low risk to the ecosystem. For human health assessment, the dietary pathway was the main pathway of exposure to arsenic in farmland soil of China. However, children's soil intake also contributed 34.48% to the exposure to arsenic, owing to their behavior. This study can provide a reference for the management of arsenic agricultural pollution in farmland soils in China.

e16096 Background: Gastric cancer (GC) is the second cause of cancer-related death and metastasis is an important cause of death. Considering difficulties in searching for metastatic driver mutations, we tried a novel strategy to identify early drivers in primary gastric tumors. In this study, we conducted an integrative genomic analysis on GC patients and identified early drivers that lead to metastases. Methods: Tumors and matched normal tissues from 400 Chinese GC patients were characterized by whole-exome sequencing (WES), transcriptome sequencing and targeted exome sequencing (TES), especially the comparative analysis results between higher metastatic potential (HMP) group with T1 stage and lymph-node metastases, and lower metastatic potential (LMP) group without lymph-nodes or distant metastases. Functional experiments on candidate driver mutations were applied in GC cell lines to explore their roles in metastasis and immune escape. Results: HMP group presented higher mutation load and heterogeneity, enrichment in immunosuppressive signaling, lower tumor purity, more stromal and immune cell infiltration than LMP group. We identified 262 differentially expressed mRNA, lncRNA and miRNA between HMP and LMP group (with more than twice proportion of 2-fold increased or decreased tumor than normal tissue in HMP than LMP group, and with significantly 2-fold higher or lower in HMP tumors than LMP tumors). 168 candidate prometastatic mutations were found by WES and 8 were selected for following TES to detect their association with distant metastasis. We found that four candidate mutations were related to distant metastasis and mutated TP53 and MADCAM1 were significantly associated with poor metastasis-free survival. It’s worth noting that though with low mutational rate, MADCAM1 mutations were only observed in patients with metastasis within three years after surgery or at diagnosis. We demonstrated that MADCAM1-mutated proteins act as GOF mutants and could not only directly promote cancer cells migration, but also could trigger tumor metastasis by establishing complicated immunosuppressive microenvironment, including promoting PD-L1-mediated immune escape and reprogramming tumor-associated macrophages (TAMs). Conclusions: Our results showed that the GCs with different metastatic potential are distinguishable at the genetic level. A number of potential metastatic driver mutations was revealed in this study including known cancer-associated genes TP53. We also discovered some novel driver mutations, such as MADCAM1. The results indicate driver mutations in early-onset metastatic GC could promote metastasis not only by directly empower cancer cells to disseminate but also by establishing an immunosuppressive microenvironment. This study increased the understanding of molecular landscape of GC patients and provided possibility for future target therapy.

Crowdsourcing has become an increasingly attractive practice for companies to abstain on-demand workforce and higher level of flexibility in open contexts. While knowledge-intensive crowdsourcing is expected to be prosperous, most current crowdsourcing calls are still about general and low-priced tasks. An obstacle of conducing knowledge-intensive crowdsourcing is the lack of diversity of expertise and the small scale of crowd in isolated crowdsourcing marketplaces. In this paper, a network of crowdsourcing marketplaces is envisioned for efficient knowledge-intensive crowdsourcing and engagement of massive and diverse participants across different marketplaces. Based on an algorithm for estimating participants for knowledge-intensive crowdsourcing tasks, an experiment with 100 simulations indicates that conducting crowdsourcing tasks in a network of crowdsourcing marketplaces results in higher customer satisfaction than doing that in isolated marketplaces. This finding advocates the development of a network of crowdsourcing marketplaces to open up the potential of knowledge-intensive crowdsourcing.

Jiangsu and Zhejiang provinces, located in the Yangtze River Delta (YRD) core region, are the most economically developed regions in China, as well as the areas with serious soil pollution. The concentrations, sources, and distributions of heavy metal(loid)s in agricultural soils of the two provinces were studied; positive matrix factorization model (PMF) analysis and kriging interpolation were combined to compare the pollution characteristics of heavy metal(loid)s. The results showed that the degree of accumulation might be more serious in Zhejiang province than in Jiangsu province, especially in terms of Cd, Hg, and Pb. PMF results showed anthropogenic activities were the dominant factors affecting the concentrations of soil heavy metal(loid)s. The contributions of the three sources in Jiangsu province were 40.28% natural and traffic sources, 37.49% agricultural sources, and 22.22% industrial and coal combustion sources. The contributions of the three sources in Zhejiang province were 43.45% agricultural and industrial sources, 32.15% natural sources, and 24.40% industrial sources. The kriging interpolation results of the two provinces showed that the concentrations of As, Cr, and Ni were significantly higher in Jiangsu province than in Zhejiang province; the concentrations of Cu were similar in the two provinces, while other heavy metals had higher concentrations in Zhejiang province. These accumulations of heavy metal(loid)s in agricultural soil in both provinces cannot be ignored. This work will contribute to the development of effective policies aimed at protecting the soil environment from long-term accumulation of heavy metal(loid)s.

Soil contamination with mercury (Hg) is a serious and widespread issue in China, with particularly severe effects on the quality of agricultural soils. To analyse long-term, nation-wide trends in Hg contamination of agriculture soil, we conducted a review of Hg concentrations in agricultural soils over four decades, based on 791 studies comprising 1411 sites, published between 1976 and 2016. We assessed spatiotemporal variations in Hg concentration, along with ecological and health risks. While Hg concentrations in agricultural soils showed an increasing trend between 1979 and 2010, they declined thereafter. Moreover, Hg concentrations in agricultural soils were generally high in western (e.g. Guizhou), southern (e.g. Hunan) and north-eastern provinces (e.g. Liaoning), where mining activities were concentrated. Using the geoaccumulation index (Igeo) and other ecological and health risk indices, we found most sampling sites to be uncontaminated, or to have a low level of contamination, although some mining sites showed moderate to extreme Hg contamination. The noncarcinogenic risk to exposure groups followed the order of children (4.42) > adult females (2.71) > adult males (2.45). Therefore, children were identified as the priority risk group. Noncarcinogenic risk values exceeded 100 in some areas in Guizhou and Hunan provinces; these areas should be prioritised for Hg control measures. This review examined Hg pollution in Chinese agricultural soils to provide insight to policymakers for the development of targeted contamination prevention measures.

Electroacupuncture (EA) point specific (ST36-37) stimulation decreases cardiovascular reflex responses through supraspinal regions such as the hypothalamic paraventricular nucleus (PVN) while mechanical stimulation of acupoints decreases pressor responses through peripheral thermal transient receptor potential vanilloid type-1 (TRPV1). Moxibustion generating heat applied at acupoint in combination with antihypertensive drugs decreases elevated blood pressure. We hypothesized that moxibustion modulates sympathoexcitatory cardiovascular responses through the hypothalamic PVN and peripheral heat sensitive TRPV1 in the absence of antihypertensive drugs. Rats were anesthetized, ventilated, and heart rate and mean blood pressure were monitored. Gastric distention induced consistent pressor reflex responses every 10-min. Thirty-minutes of bilateral moxibustion at the acupoint ST36, overlying the deep peroneal nerves, reduced the gastric distention evoked elevation in blood pressure. Blood pressure reflex responses were not reduced by both EA and moxibustion at G39. The moxibustion inhibition but not EA inhibition of the cardiovascular responses was reversed with blockade of local heat sensitive TRPV1 at ST36. Accordingly, activation of thermal TRPV1 by moxibustion at an average of 44.2°C in contrast to 40°C reduced the pressor responses. Naloxone, an opioid receptor antagonist, microinjected into PVN inhibited transiently the effect of moxibustion. Thus, activation of peripheral heat sensitive TRPV1 mediated the moxibustion-inhibition, but not EA-inhibition, of sympathoexcitatory cardiovascular reflex responses through hypothalamic PVN opioid system.

The first national-scale assessment of lead (Pb) contamination in agricultural soils across China was conducted based on >1900 articles published between 1979 and 2016. Pb concentrations, temporal and spatial variations, and influencing factors were analyzed. Children's blood lead levels (BLLs) were also estimated using the integrated exposure uptake biokinetic (IEUBK) model. Pb concentrations in different areas of China varied greatly, which was closely associated with the distribution of Pb-related industries, especially Pb-zinc mine smelting, non-ferrous polymetallic mine smelting, e-waste recycling, and leaded gasoline consumption. The year 2000 was a significant transition year for Pb concentrations, with a rapid increase pre-2000 and a subsequent slow upward trend. Pb concentrations were found to be strongly associated with indicators of economic and social development including gross domestic product (GDP), population size, and vehicle ownership. Leaded gasoline, coal combustion, and non-ferrous smelting were the main sources of atmospheric Pb during the different periods. Predicted BLLs were higher in South China than those in the north. This study details the overall Pb contamination status of agricultural soils in China, and thus provides insights for policymakers with respect to pollution prevention measures. Keywords: Lead, Agricultural soils, Influence factors, China, Tempo-spatial variations, BLLs

The first national-scale assessment of chromium (Cr) contamination in China’s agricultural soils was performed based on 1625 sites analysed with 1799 previously published papers. Spatial and temporal variations were assessed, and the ecological risk was estimated. The range of Cr concentrations in farmland soil is 1.48–820.24 mg/kg. At approximately 4.31% and 0.12% of the sampling sites, Cr concentrations exceeded the screening value (150 mg/kg) and the control value (800 mg/kg), respectively (GB15618-2018). Cr concentrations decreased in the following order: Southwest > Northwest > East > South > Northeast > Central > North China. Moreover, the Cr accumulation rate in agricultural soils may have decreased during 2011–2016, possibly due to government-led changes in China’s industrial structure and policies limiting the discharge of polluted industrial wastes. Linear correlations were observed between the application amounts of fertilizers and Cr concentrations in the soil, indicating that the application of nitrogen, phosphorus and potassium fertilizers is an important contributor of Cr in agricultural soils. Additionally, geoaccumulation index (Igeo) values for Cr showed that more than 83.4% of the sampling sites were uncontaminated, with high Igeo values distributed in some areas, especially those with mining and electroplating industries. Overall, this study details the Cr contamination status of agricultural soils in China and provides insights for policymakers enacting measures to prevent pollution.

Background Surgical resection of patients with resectable Stage IV colorectal cancer (CRC) is regarded as first choice if possible. However, its influence on overall survival (OS) has not been thoroughly explored. In this study, we aimed to construct nomograms to help predict 1-, 3- and 5-year OS rate and colorectal cancer-specific survival (CCSS) rate. Methods A total of 2996 cases who underwent primary and metastatic resection were selected in the study from surveillance, epidemiology and end results (SEER) database. About 48 Stage IV CRC patients after resection from the Fudan University Shanghai Cancer Center (FUSCC) were assigned as an independent external validation group. Log-rank and multivariate Cox regression analysis were used. The competing-risks model was used to estimate the cumulative incidence of death. Nomograms were built for prediction of OS and CCSS after surgical resection in patients with Stage IV CRC. Results The 1-, 3- and 5-year probabilities of OS were 76.6%, 41.4% and 23.2%, respectively. The 1-, 3- and 5-year colorectal cumulative incidence of death were 23.0%, 54.9% and 71.3%, respectively. The calibration curves for probability of 1-, 3- and 5-year OS and CCSS showed optimal agreement between nomogram prediction and actual observation, and the Harrell's C-indexes for the nomograms to predict OS and CCSS were 0.662 and 0.650, respectively. For FUSCC validation set, the C-index for this model to predict OS was 0.657. Conclusion Nomograms for prediction of OS and CCSS of patients with Stage IV CRC who underwent primary and metastatic resection were built. Performance of the model was excellent. These nomograms may be helpful for patients and physicians when making a decision.

Purpose– The purpose of this paper is to demystify Lean for service innovation by investigating its benefits and risks. Lean innovation is a relatively new approach which is advocated in management literature. Little scientific work about its practice exists in the field. Although the Lean innovation principles are clear, there is limited evidence about their impact on service innovation processes.Design/methodology/approach– From the knowledge-based view (KBV) of the firm, a framework for understanding Lean innovation is developed. Using this framework, the benefits and risks of Lean innovation are analyzed in a case study.Findings– The case study not only shows that Lean service innovation can have many advantages, but also draws attention to the risks. The risks might result in the inability to follow Lean principles and might hamper the realization of the benefits. Using the case studies, study mitigation mechanisms are identified.Originality/value– This research offers a new knowledge perspective and a better understanding of Lean service innovation. There are two main contribution of this paper. First of all, it reports on the impact of Lean innovation on a bank’s innovation processes, both its benefit and risks. This has a contribution to understanding the innovation process in service organizations. Second, this paper extends Lean innovation to a service context and contributes to the knowledge basis of Lean innovation.

Governments need to adapt to changes in their internal and external environments and create systems that allow them to scan trends, identify developments, predict their potential impact on the organization, and quickly learn how to implement changes to their standard operating procedures. As a response, government organizations are adopting agile approaches as part of their process redesigns, project management, and software development approaches. Although agility and adaptiveness are long in use in the private sector, they have been increasingly adopted in the public sector literature and practices. In order to understand the existing theoretical and practical foundations of the field, we have conducted a systematic literature review and identified four streams of research areas: (1) software development approaches, (2) project management approaches, (3) application areas, and (4) potential outcomes. In this article, we synthesize this literature, provide an outlook on future research questions, and introduce several articles as part of the current special issue focused on agile government.

Heavy metal pollution of agricultural soils is an important issue around the world. To understand the overall pollution process, accurate determination of every input and output pathway of heavy metals to and from soils is essential. Hence, input and output inventory, a quantitative analysis method of heavy metals balance in agricultural soils, has been widely used. However, due to differences in geography, climate, socioeconomic factors, industrial and agricultural production, substantial variation exists among existing input and output inventories for different countries and regions. In this study, we systematically analyzed these differences and the findings will improve the compilation of inventories worldwide.

Purpose: We explored the influence of age on clinicopathologic features and survival of patients with M0 gastric cancer (GC). Methods: 16856 GC patients from Surveillance, Epidemiology and End Results (SEER) database and 1037 GC patients from Chinese multiple centers were enrolled in the U.S. and Chinese cohort, respectively. 50-year-old was treated as cutoff age. Propensity score method was used to carry out a 1:1 paired match. Results: In the U.S. cohort, we found that younger patients presented poor tumor behavior. However, in spite of worse outcome in stage I~IV cohort, young group showed better 3-year survival in M0 patients, especially for those who underwent a total gastrectomy. In a matched analysis, a better prognosis was still observed in younger group. The prognostic value of age was also validated in M0 GC patients with gastrectomy in Chinese cohort. Conclusions: In spite of the worse outcome in survival curve of stage I~IV GC cohort, young patients with gastrectomy presented favorable survival in M0 subgroup. It is also applicable in China. Early diagnosis and treatment should be taken seriously in young GC patients since they often possess poorer characteristics but benefited more from gastrectomy.

Governments from all over the world are struggling to take advantage of big data developments. Enterprise Architecture (EA) can be used as an instrument to integrate big data (BD) in the existing business processes and ICT-landscape. In this policy paper, we explore the role of EA in the adoption of BD. For this, we adopted a qualitative case study approach and investigated a large administrative organization that was in the process of adopting BD. We found in our case study that the first attempts were focused on integrating big data in the current landscape, but this encountered too many challenges that halt progress. To overcome the challenges, a separate BD department and accompanying infrastructure was created. The strategy was first to reap the benefits of BD and to understand what should be done, and thereafter integrating the working systems in the existing landscape. The findings suggest that current infrastructures might not be suitable for integrating BD and substantial changes are needed first. In the case the role of BD needed to be first clarified before EA could play a role in adopting BD. EA should deal with the uncertainties and complexities by ensuring a configurable landscape, by providing an incremental approach for adapting the infrastructure step-by-step, before the benefits of big data can be gained. Developing an incremental migration plan was found to be a key aspect for the adoption of BD.

Law-making is inextricably bound up with the developments of e-government. Yet translating legislation into administrative processes and services has been extremely complex, taking a long time and involving many manual tasks. This problem is further complicated by the increasing amount of legislation and the frequent changes of legislation. Recent technology innovations enable a shift from implementation and maintenance of e-government services by software configuration and engineering towards implementation and maintenance based on knowledge representation. Despite the many benefits such as faster, cheaper and easier implementation, adoption has been limited. In this paper we describe these developments and compare software-based with knowledge-based implementation and maintenance. Based on a case study, we identify success factors and challenges from moving towards knowledge-based implementation and maintenance in the aspects of motivation, architecture, technique, expertise and finance.

In today's economy managers expect new strategies and policies to be implemented quickly. Yet practice shows that current systems are not able to implement changes within a short time frame. Nowadays a variety of technologies including semantic web services, business rules and software agents are available as building blocks for interoperable systems. Yet these technologies are rarely used in combination and are not adapting operational processes to changing business strategies and other requirements. A generic architecture is presented in this paper which is able to adapt processes to changing requirements based on three types of knowledge repositories (domain ontology, service description and business rule) which, when combined, allows for direct employment of strategy in business processes. The architecture is tested using scenarios. The testing shows that the architecture improves the interoperability between policy/strategic and operational level and results in a higher agility and better compliance.

The combination of social media and Business Process Management (BPM) has given rise to the emerging field of “social BPM”. The new development of social BPM is expected to provide benefits like flexibility for knowledge-intensive processes, like policy-making. The goal of this paper is to understand the impact of social BPM on policy-making. We first present a literature survey showing that social BPM is a new and emerging research area and limited attention has been given to social BPM in egovernment. The literature reviews showed a lack of empirical research into the accomplished benefits of social BPM. To bridge this gap, a comprehensive case study in a Dutch government social BPM platform was conducted. While not all the benefits suggested in the literature were identified in the case study, negative impact of social BPM were also found. A tension was found between accomplishing flexibility and accountability and user efficiency.

Organizations are required to comply with changes in legislation and policy. Yet the implementation of new legislation is often expensive, can have long lead times and is prone to failure. The existing situation significantly constrains policy-making. To improve this, policy makers and policy executors are searching for ways to achieve higher levels of flexibility and agility in their business process management systems. Flexibility is the ability to react to changes and agility is the speed in responding to variety and change. Both flexibility and agility are multi-dimensional concepts. This paper presents principles for creating flexibility and agility when implementing new or revised policies into business processes. These principles include: 1) defining and using business services, 2) integrating and orchestrating business services through the use of events, 3) separating process, knowledge and resources and 4) implementing policy in an integrated manner. Business services are components encapsulating business functions and having clear responsibilities and accountabilities. The case study shows that these forms of flexibility and agility can help to implement policies more quickly and cost effectively. An organization's resources and level of flexibility and agility determines what laws can be implemented within a certain time. The improvement of flexibility and agility requires innovations on all levels: infrastructure, business process and organization. The level of flexibility and agility should always be measured by a combination of measures. We make plea for instruments assessing the impact of policies on organizations prior to implementation.

Software agents and rules are both used for creating flexibility. Exchanging rules between Semantic Web and agents can ensure consistency in rules and support easy updating and changing of rules. The Rule Interchange Format (RIF) is a new W3C recommendation Semantic Web standard for exchanging rules among disparate systems. Yet, the contribution of RIF in rules exchange between Semantic Web and software agents is unclear. The BDI architectural style is regarded as the predominant approach for the implementation of intelligent agents. This paper proposes a development for integrating RIF and BDI agents to enhance agent reasoning capabilities. This approach consists of an integration architecture and equivalence principles for rule translation. The equivalence principles are demonstrated using examples. The results show that the approach allows the integration of RIF with BDI agent programming and realize the translation between the two systems.

For decades, information systems have been designed for controlling and managing business processes. In the past, these systems were often monolithic in nature and not made for interacting and communicating with other systems. Today, departments and organizations must collaborate, which requires distributed Web-based systems to support the enactment of flexible business processes. In this paper, four architectures of process management systems are investigated by studying the components and the relationships with the tasks that make up the business processes. These different architectures support automation of non-repetitive, customized processes, and are compared based on dimensions of flexibility. This evaluation showed that the process orchestration architecture scored best, but still has its shortcomings. The results from the comparison are used for developing a research agenda that includes the suggestion to develop reference architecture for connecting individual architectural components.

This study aimed to investigate the optimal degree of weight gain across the gestational spectrum in 1971 children enrolled at birth and followed up to age 7 years. Weight gain in infancy was categorized into four groups based on weight gain z-scores: slow (1.28). Underweight and overweight or obesity (OWO) were defined as a body mass index ≤5th and ≥85th percentile, respectively, for age and gender. In our population, OWO was far more common than underweight (39.7% vs. 3.6%). Weight gain tracked strongly from age 4 to 24 months, and was positively associated with OWO and an unfavorable pattern of metabolic biomarkers, although the degree of weight gain for the risk was different across gestational categories. Extremely rapid weight gain led to a particularly high risk of OWO among children born early term and late preterm: odds ratio: 3.3 (95% confidence interval: 1.9 to 5.5) and 3.7 (1.8 to 7.5), respectively, as compared to those with on track weight gain. Our findings suggest that monitoring and ensuring optimal weight gain across the entire gestational spectrum beginning from birth represents a first step towards primary prevention of childhood obesity.

Crowdsourcing has become an increasingly attractive practice for companies to execute business processes in open contexts with on-demand workforce and higher level of flexibility. One of the challenges is the identification of the best-fit crowdsourcing participant from a group of online candidates. This paper presents a method of AHP-TOPSIS based on Grey Relation Analysis for estimating participants of a crowdsourcing task based on their online profiles and proposals. This method is tested by an experiment on a dataset of 348 completed IT service crowdsourcing tasks. An analysis on the matching between the test result and the actual selection result reveals the accuracy and efficiency of this method. Companies can use this method to facilitate the quality control at the beginning of crowdsourcing and keeps the selection of participants easy. This paper contributes to the design of a software agent for crowdsourcing platforms to automatically rank the participants of a task.

Adapting to and complying with frequently changing legislation quickly against low costs requires organizations to adapt their business processes automatically. Semantic representation of legal knowledge is a prerequisite for the automatic creation of business processes. Business Rules BR can be used to capture legal knowledge and business processes can be created by selecting, composing and invoking Semantic Web Services SWS. In this paper, a modeling framework is presented that enables the automatic creation of business process by invoking SWSs. Process creation is conducted by BRs derived from legislation. The framework addresses the modeling of legal knowledge representation and service descriptions that are required for creating operational processes at runtime. The framework is briefly illustrated by a legislation implementation case study which shows how compliance between business processes and legislation is ensured.

IT service innovation is often dependent upon the relationship with outsourcing vendors. In such situations innovation is a result of knowledge accessing and utilization between outsourcing provider and user. As a management thinking, the application of Lean principles can facilitate knowledge accessing and utilization to enable IT service innovation for the customer. Based on the knowledge-based view of the firm, we developed a conceptual framework to describe how Lean can drive IT service innovation within IT outsourcing relationships. This framework is used to analyze the use of Lean principles in an explorative case study of a service organization and its two IT outsourcing providers. The framework and the case study show that IT service innovation is an ongoing process. A clear strategic direction and learning environment are critical to achieve it. Applying Lean principles facilitates the learning behaviors and allows smooth communication on innovative ideas and in this way drive innovation.

Adapting to and complying with frequently changing policy against low costs requires flexible business processes. Yet, existing systems are unrelated, consist of operating silos, involve many human translation tasks and policies are hardcoded in business processes. From a technology perspective, both Semantic Web Service (SWS) and Business Rule (BR) can be used to create flexible business processes that can adapt to changes in policy. Despite their potential these technologies are seldom integrated or used in administrative organizations. SWS can be adopted to present functionality needed in processes, whereas the elicitation of BR is an important ingredient for process creation. In this paper, we derive and test guidelines for creating administrative processes that are dynamical created using SWSs and BRs that are derived from policies. A case study is used to demonstrate and evaluate the guidelines. The guidelines can serve as a foundation for developing agile and compliant architectures.

Service Oriented Architecture (SOA) and Business Rules (BR) are used by organization to adapt to changes. The disadvantage of this approach is that processes need to be defined in advance often requiring labor-intensive and time-consuming modeling processes. Usually, only a limited number of variations in processes are supported which have to be defined in design time. Hence, a shift from static to dynamic business processes creation is required. Semantic Web Services (SWS) can be used as a technology to create dynamic processes. Although there has been extensive research in the field of SWS and BR, there is scant research on the combination of them. In this paper, we propose an architecture based on BR and SWS to create dynamic business processes. Using a pre-agreed domain ontology to ensure the compatibility between SWSs and BRs, a new process is created by selecting the decision services using BRs and composing decision services with necessary assistant services. An illustrative study is used to demonstrate and evaluate the architecture on its feasibility in dynamic process creation. In this way, SOA systems in government environment can create a process with their services dynamically without having to hardcode the process. This can help the organization to efficiently adapt to changes in policies and legislation.

Business rules and software agents can be used for creating flexible business processes. The Rule Interchange Format (RIF) is a new W3C recommendation standard for exchanging rules among disparate systems. Yet, the impact that the introduction of RIF has on the design of flexible business processes is unclear. Intelligent software agents can be used to create dynamic business processes. The BDI architectural style is regarded as the predominant approach for the implementation of intelligent agents. It is expected that using RIF can enhance the reasoning capability of agents. Yet, these two developments are not connected. In this research, an approach is developed for integrating RIF and BDI agents. This approach consists of an integration architecture and equivalence principles for rule translation. The equivalence principles are demonstrated using examples. The results show that the approach allows the integration of RIF with BDI agent programming and in this way enhances agent reasoning capabilities.

In their attempt to improve their systems and architectures, organizations need to be aware of the types of flexibility and agility and the current level of each type of flexibility and agility. Flexibility is the general ability to react to changes, whilst agility is the speed in responding to variety and changes Both flexibility and agility are diverse concepts that are hard to grasp. In this paper the types of flexibility and agility of business processes is discussed on a foundation level and an approach to measure the level of flexibility and agility is proposed. A case study of the flexibility and agility measurement is used to demonstrate the approach. The illustration is used to discuss the difficulties and limitations of the measurement approach.There is no uniform definition of or view on flexibility and agility. This makes it hard to develop a measurement approach. Furthermore, as business processes can be different, this might result in different metrics for measuring the level of flexibility and agility. There is no single measure and for each type of business process and flexibility and agility should always measure by a combination of metrics. In addition, both qualitative and quantitative metrics should be used to measure the level of flexibility and agility.

In today’s ever changing environment organizations need flexibility and agility to be able to deal with changes. Flexibility is necessary to adapt to changes in their environment, whilst agility is needed to rapidly response to changing customer demands. In this paper a mechanism based on the separation of knowledge rules, process rules and information resources is proposed to enhance the flexibility and agility of business processes. Agent-based simulation is employed to test and evaluate if the necessary flexibility and agility can be created using these mechanisms. In the agent-based simulation the clients and organization entities are simulated, whilst the separation of knowledge rules, process rules and information sources is implemented. Three changes have been evaluated using the simulation. Flexibility and agility proved to be dependent on good system design based on the separation of knowledge rules, process rules and information sources, as well as on the human resources and capabilities executing tasks. Agent-based simulation proved to be a suitable tool for evaluating the level of flexibility and agility prior to real implementation.