Macrophage inhibitory cytokine-1 (MIC-1/GDF15) slows cancer development but increases metastases in TRAMP prostate cancer prone mice

Macrophage inhibitory cytokine-1 (MIC-1/GDF15), a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa) and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1fms) to produce syngeneic TRAMPfmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1fms and syngeneic C57BL/6 mice. Whilst TRAMPfmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU) tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

Paradoxical roles of tumour necrosis factor-alpha in prostate cancer biology

Tumour necrosis factor (TNF) is a pleiotropic cytokine with dual roles in cancer biology including prostate cancer (PCa). On the one hand, there is evidence that it stimulates tumour angiogenesis, is involved in the initiation of PCa from an androgen-dependent to a castrate resistant state, plays a role in epithelial to mesenchymal plasiticity, and may contribute to the aberrant regulation of eicosanoid pathways. On the other hand, TNF has also been reported to inhibit neovascularisation, induce apoptosis of PCa cells, and stimulate anti-tumour immunity. Much of the confusion surrounding its seemingly paradoxical roles in cancer biology stems from the dependence of its effects on the biological model within which TNF is investigated. This review will address some of these issues, and also discuss on the therapeutic implications.

A multivariate approach to the identification of surrogate parameters for heavy metals in stormwater

Stormwater is a potential and readily available alternative source for potable water in urban areas. However, its direct use is severely constrained by the presence of toxic pollutants, such as heavy metals (HMs). The presence of HMs in stormwater is of concern because of their chronic toxicity and persistent nature. In addition to human health impacts, metals can contribute to adverse ecosystem health impact on receiving waters. Therefore, the ability to predict the levels of HMs in stormwater is crucial for monitoring stormwater quality and for the design of effective treatment systems. Unfortunately, the current laboratory methods for determining HM concentrations are resource intensive and time consuming. In this paper, applications of multivariate data analysis techniques are presented to identify potential surrogate parameters which can be used to determine HM concentrations in stormwater. Accordingly, partial least squares was applied to identify a suite of physicochemical parameters which can serve as indicators of HMs. Datasets having varied characteristics, such as land use and particle size distribution of solids, were analyzed to validate the efficacy of the influencing parameters. Iron, manganese, total organic carbon, and inorganic carbon were identified as the predominant parameters that correlate with the HM concentrations. The practical extension of the study outcomes to urban stormwater management is also discussed.

A critical evaluation and comparison of two formative measures of system quality using criterion variables

Evaluating the validity of formative variables has presented ongoing challenges for researchers. In this paper we use global criterion measures to compare and critically evaluate two alternative formative measures of System Quality. One model is based on the ISO-9126 software quality standard, and the other is based on a leading information systems research model. We find that despite both models having a strong provenance, many of the items appear to be non-significant in our study. We examine the implications of this by evaluating the quality of the criterion variables we used, and the performance of PLS when evaluating formative models with a large number of items. We find that our respondents had difficulty distinguishing between global criterion variables measuring different aspects of overall System Quality. Also, because formative indicators “compete with one another” in PLS, it may be difficult to develop a set of measures which are all significant for a complex formative construct with a broad scope and a large number of items. Overall, we suggest that there is cautious evidence that both sets of measures are valid and largely equivalent, although questions still remain about the measures, the use of criterion variables, and the use of PLS for this type of model evaluation.

Extending and validating the is-impact model in Saudi Arabia : accounting for computer network quality

Organizations from every industry sector seek to enhance their business performance and competitiveness through the deployment of contemporary information systems (IS), such as Enterprise Systems (ERP). Investments in ERP are complex and costly, attracting scrutiny and pressure to justify their cost. Thus, IS researchers highlight the need for systematic evaluation of information system success, or impact, which has resulted in the introduction of varied models for evaluating information systems. One of these systematic measurement approaches is the IS-Impact Model introduced by a team of researchers at Queensland University of technology (QUT) (Gable, Sedera, & Chan, 2008). The IS-Impact Model is conceptualized as a formative, multidimensional index that consists of four dimensions. Gable et al. (2008) define IS-Impact as "a measure at a point in time, of the stream of net benefits from the IS, to date and anticipated, as perceived by all key-user-groups" (p.381). The IT Evaluation Research Program (ITE-Program) at QUT has grown the IS-Impact Research Track with the central goal of conducting further studies to enhance and extend the IS-Impact Model. The overall goal of the IS-Impact research track at QUT is "to develop the most widely employed model for benchmarking information systems in organizations for the joint benefit of both research and practice" (Gable, 2009). In order to achieve that, the IS-Impact research track advocates programmatic research having the principles of tenacity, holism, and generalizability through extension research strategies. This study was conducted within the IS-Impact Research Track, to further generalize the IS-Impact Model by extending it to the Saudi Arabian context. According to Hofsted (2012), the national culture of Saudi Arabia is significantly different from the Australian national culture making the Saudi Arabian culture an interesting context for testing the external validity of the IS-Impact Model. The study re-visits the IS-Impact Model from the ground up. Rather than assume the existing instrument is valid in the new context, or simply assess its validity through quantitative data collection, the study takes a qualitative, inductive approach to re-assessing the necessity and completeness of existing dimensions and measures. This is done in two phases: Exploratory Phase and Confirmatory Phase. The exploratory phase addresses the first research question of the study "Is the IS-Impact Model complete and able to capture the impact of information systems in Saudi Arabian Organization?". The content analysis, used to analyze the Identification Survey data, indicated that 2 of the 37 measures of the IS-Impact Model are not applicable for the Saudi Arabian Context. Moreover, no new measures or dimensions were identified, evidencing the completeness and content validity of the IS-Impact Model. In addition, the Identification Survey data suggested several concepts related to IS-Impact, the most prominent of which was "Computer Network Quality" (CNQ). The literature supported the existence of a theoretical link between IS-Impact and CNQ (CNQ is viewed as an antecedent of IS-Impact). With the primary goal of validating the IS-Impact model within its extended nomological network, CNQ was introduced to the research model. The Confirmatory Phase addresses the second research question of the study "Is the Extended IS-Impact Model Valid as a Hierarchical Multidimensional Formative Measurement Model?". The objective of the Confirmatory Phase was to test the validity of IS-Impact Model and CNQ Model. To achieve that, IS-Impact, CNQ, and IS-Satisfaction were operationalized in a survey instrument, and then the research model was assessed by employing the Partial Least Squares (PLS) approach. The CNQ model was validated as a formative model. Similarly, the IS-Impact Model was validated as a hierarchical multidimensional formative construct. However, the analysis indicated that one of the IS-Impact Model indicators was insignificant and can be removed from the model. Thus, the resulting Extended IS-Impact Model consists of 4 dimensions and 34 measures. Finally, the structural model was also assessed against two aspects: explanatory and predictive power. The analysis revealed that the path coefficient between CNQ and IS-Impact is significant with t-value= (4.826) and relatively strong with â = (0.426) with CNQ explaining 18% of the variance in IS-Impact. These results supported the hypothesis that CNQ is antecedent of IS-Impact. The study demonstrates that the quality of Computer Network affects the quality of the Enterprise System (ERP) and consequently the impacts of the system. Therefore, practitioners should pay attention to the Computer Network quality. Similarly, the path coefficient between IS-Impact and IS-Satisfaction was significant t-value = (17.79) and strong â = (0.744), with IS-Impact alone explaining 55% of the variance in Satisfaction, consistent with results of the original IS-Impact study (Gable et al., 2008). The research contributions include: (a) supporting the completeness and validity of IS-Impact Model as a Hierarchical Multi-dimensional Formative Measurement Model in the Saudi Arabian context, (b) operationalizing Computer Network Quality as conceptualized in the ITU-T Recommendation E.800 (ITU-T, 1993), (c) validating CNQ as a formative measurement model and as an antecedent of IS Impact, and (d) conceptualizing and validating IS-Satisfaction as a reflective measurement model and as an immediate consequence of IS Impact. The CNQ model provides a framework to perceptually measure Computer Network Quality from multiple perspectives. The CNQ model features an easy-to-understand, easy-to-use, and economical survey instrument.

In pursuit of tourism destination brand loyalty : visitor relationship management orientation of destination marketing organisations

The proposition underpinning this study is engaging in meaningful dialogue with previous visitors represents an efficient and effective use of resources for a destination marketing organization (DMO), compared to above the line advertising in broadcast media. However there has been a lack of attention in the tourism literature relating to destination switching, loyalty and customer relationship management (CRM) to test such a proposition. This paper reports an investigation of visitor relationship marketing (VRM) orientation among DMOs. A model of CRM orientation, which was developed from the wider marketing literature and a prior qualitative study, was used to develop a scale to operationalise DMO visitor relationship orientation. Due to a small sample, the Partial Least Squares (PLS) method of structural equation modelling was used to analyse the data. Although the sample limits the ability to generalise, the results indicated the DMOs’ visitor orientation is generally responsive and reactive rather than proactive.

Extracorporeal lessons from sheep

Background: Extracorporeal circulation (ECC), the diversion of blood flow through a circuit located outside of the body, has been one of the major advances in modern medicine. Cardio-pulmonary bypass (CPB), renal dialysis, apheresis and extracorporeal membrane oxygenation (ECMO) are all different forms of ECC. Despite its major benefits, when blood comes into contact with foreign material, both the coagulation and inflammation cascades are activated simultaneously. Short periods of exposure to ECC e.g. CPB (�2 h duration), are known to be associated with haemolysis, coagulopathies, bleeding and inflammation which demand blood product support. Therefore, it is not unexpected that these complications would be exaggerated with prolonged periods of ECC such as in ECMO (days to weeks duration). The variability and complexities of the underlying pathologies of patients requiring ECC makes it difficult to study the cause and effect of these complications. To overcome this problem we developed an ovine (sheep) model of ECC. Method: Healthy female sheep (1–3 y.o.) weighing 40–50 kg were fasted overnight, anaesthetised, intubated and ventilated [1]. Half the group received smoke induced acute lung injury (S-ALI group) (n = 8) and the other half did not (healthy group) (n = 8). Sheep were subsequently cannulated (Medtronic Inc, Minneapolis, MN, USA) and veno-venous ECMO commenced using PLS ECMO circuit and Quadrox D oxygenator (Maquet Cardiopulmonary AG, Hechinger Straße, Germany). There was continuous physiological monitoring and blood was collected at specified time intervals for full blood counts, platelet function analysis (by Multiplate®), routine coagulation and assessment of clot formation and lysis (by ROTEM®). Preliminary results Full blood counts and routine coagulation results from normal healthy sheep were comparable to those of normal human adults. Within 15 min of initiating of ECMO, PT, PTT and EXTEM clot formation time increased, whilst EXTEM maximum clot firmness decreased in both cohorts. Discussion & Conclusions: Preliminary results of sheep from both 2 h ECMO cohorts showed that the anatomy, haematology and coagulation parameters of an adult sheep are comparable to that a human adult. Experiments are currently underway with healthy (n = 8) and S-ALI (n = 8) sheep on ECMO for 24 h. In addition to characterising how ECMO alters haematology and coagulation parameters, we hope that it will also define which blood components will be most effective to correct bleeding or clotting complications during ECMO support.

Sources of ultrafine particles and chemical species along a traffic corridor : comparison of the results from two receptor models

Particulate matter is common in our environment and has been linked to human health problems particularly in the ultrafine size range. A range of chemical species have been associated with particulate matter and of special concern are the hazardous chemicals that can accentuate health problems. If the sources of such particles can be identified then strategies can be developed for the reduction of air pollution and consequently, the improvement of the quality of life. In this investigation, particle number size distribution data and the concentrations of chemical species were obtained at two sites in Brisbane, Australia. Source apportionment was used to determine the sources (or factors) responsible for the particle size distribution data. The apportionment was performed by Positive Matrix Factorisation (PMF) and Principal Component Analysis/Absolute Principal Component Scores (PCA/APCS), and the results were compared with information from the gaseous chemical composition analysis. Although PCA/APCS resolved more sources, the results of the PMF analysis appear to be more reliable. Six common sources identified by both methods include: traffic 1, traffic 2, local traffic, biomass burning, and two unassigned factors. Thus motor vehicle related activities had the most impact on the data with the average contribution from nearly all sources to the measured concentrations higher during peak traffic hours and weekdays. Further analyses incorporated the meteorological measurements into the PMF results to determine the direction of the sources relative to the measurement sites, and this indicated that traffic on the nearby road and intersection was responsible for most of the factors. The described methodology which utilised a combination of three types of data related to particulate matter to determine the sources could assist future development of particle emission control and reduction strategies.

Load-unloading response of intact and artificially degraded articular cartilage correlated with near infrared (NIR) absorption spectra

The conventional mechanical properties of articular cartilage, such as compressive stiffness, have been demonstrated to be limited in their capacity to distinguish intact (visually normal) from degraded cartilage samples. In this paper, we explore the correlation between a new mechanical parameter, namely the reswelling of articular cartilage following unloading from a given compressive load, and the near infrared (NIR) spectrum. The capacity to distinguish mechanically intact from proteoglycan-depleted tissue relative to the "reswelling" characteristic was first established, and the result was subsequently correlated with the NIR spectral data of the respective tissue samples. To achieve this, normal intact and enzymatically degraded samples were subjected to both NIR probing and mechanical compression based on a load-unload-reswelling protocol. The parameter δ(r), characteristic of the osmotic "reswelling" of the matrix after unloading to a constant small load in the order of the osmotic pressure of cartilage, was obtained for the different sample types. Multivariate statistics was employed to determine the degree of correlation between δ(r) and the NIR absorption spectrum of relevant specimens using Partial Least Squared (PLS) regression. The results show a strong relationship (R(2)=95.89%, p<0.0001) between the spectral data and δ(r). This correlation of δ(r) with NIR spectral data suggests the potential for determining the reswelling characteristics non-destructively. It was also observed that δ(r) values bear a significant relationship with the cartilage matrix integrity, indicated by its proteoglycan content, and can therefore differentiate between normal and artificially degraded proteoglycan-depleted cartilage samples. It is therefore argued that the reswelling of cartilage, which is both biochemical (osmotic) and mechanical (hydrostatic pressure) in origin, could be a strong candidate for characterizing the tissue, especially in regions surrounding focal cartilage defects in joints.

Dynamic capabilities and performance : strategy, structure and environment

Dynamic capabilities are widely considered to incorporate those processes that enable organizations to sustain superior performance over time. In this paper, we argue theoretically and demonstrate empirically that these effects are contingent on organizational structure and the competitive intensity in the market. Results from partial least square structural equation modeling (PLS-SEM) analyses indicate that organic organizational structures facilitate the impact of dynamic capabilities on organizational performance. Furthermore, we find that the performance effects of dynamic capabilities are contingent on the competitive intensity faced by firms. Our findings demonstrate the performance effects of internal alignment between organizational structure and dynamic capabilities, as well as the external fit of dynamic capabilities with competitive intensity. We outline the advantages of PLS-SEM for modeling latent constructs, such as dynamic capabilities, and conclude with managerial implications.

The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.

Exploring subscription renewal intention of operational cloud enterprise systems - a stakeholder perspective

Retaining customers is a relevant topic throughout all service industries. However, only limited attention has been directed towards studying the antecedents of subscription renewal in the context of operational cloud enterprise systems. Cloud services have historically been offered as subscription-based services with the (theoretical) possibility of seamless service cancellation, in contrast to classical IT-Outsourcing contracts or license-based software installations of on-premise enterprise systems. In this work, we investigate the central concept of subscription renewal by focusing on different facets of IS success and their relevance for distinct employee cohorts. Analyzing inter-cohort differences has strong practical implications, as it helps IT vendors to focus on specific IT-related factors when trying to retain customers. Therefore an empirical study was undertaken. The hypotheses were developed on an individual level and tested using survey responses of IT decision makers within companies which adopted cloud enterprise systems. Gathered data was then analyzed using PLS. The results show that subscription renewal intention of the strategic cohort is mainly based on perceived system quality, whereas information quality explains most of the variance of subscription renewal in the management cohort. Beneath the cloud enterprise systems specific contributions, the work adds to the theoretical body of research related to IS success and IS continuation, as well as stakeholder perspectives.

Thyroxine and reserpine-induced changes in metabolic profiles of rat urine and the therapeutic effect of Liu Wei Di Huang Wan detected by UPLC-HDMS

The promise of metabonomics, a new "omics" technique, to validate Chinese medicines and the compatibility of Chinese formulas has been appreciated. The present study was undertaken to explore the excretion pattern of low molecular mass metabolites in the male Wistar-derived rat model of kidney yin deficiency induced with thyroxine and reserpine as well as the therapeutic effect of Liu Wei Di Huang Wan (LW) and its separated prescriptions, a classic traditional Chinese medicine formula for treating kidney yin deficiency in China. The study utilized ultra-performance liquid chromatography/electrospray ionization synapt high definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) in both negative and positive electrospray ionization (ESI). At the same time, blood biochemistry was examined to identify specific changes in the kidney yin deficiency. Distinct changes in the pattern of metabolites, as a result of daily administration of thyroxine and reserpine, were observed by UPLC-HDMS combined with a principal component analysis (PCA). The changes in metabolic profiling were restored to their baseline values after treatment with LW according to the PCA score plots. Altogether, the current metabonomic approach based on UPLC-HDMS and orthogonal projection to latent structures discriminate analysis (OPLS-DA) indicated 20 ions (14 in the negative mode, 8 in the positive mode, and 2 in both) as "differentiating metabolites".

Metabolic urinary profiling of alcohol hepatotoxicity and intervention effects of Yin Chen Hao Tang in rats using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

This paper was designed to study metabonomic characters of the hepatotoxicity induced by alcohol and the intervention effects of Yin Chen Hao Tang (YCHT), a classic traditional Chinese medicine formula for treatment of jaundice and liver disorders in China. Urinary samples from control, alcohol- and YCHT-treated rats were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) in positive ionization mode. The total ion chromatograms obtained from the control, alcohol- and YCHT-treated rats were easily distinguishable using a multivariate statistical analysis method such as the principal components analysis (PCA). The greatest difference in metabolic profiling was observed from alcohol-treated rats compared with the control and YCHT-treated rats. The positive ions m/z 664.3126 (9.00 min) was elevated in urine of alcohol-treated rats, whereas, ions m/z 155.3547 (10.96 min) and 708.2932 (9.01 min) were at a lower concentration compared with that in urine of control rats, however, these ions did not indicate a statistical difference between control rats and YCHT-treated rats. The ion m/z 664.3126 was found to correspond to ceramide (d18:1/25:0), providing further support for an involvement of the sphingomyelin signaling pathway in alcohol hepatotoxicity and the intervention effects of YCHT.