A Model-Driven Architecture Approach to the Efficient Identification of Services on Service-oriented Enterprise Architecture

Service-Oriented Enterprise Architecture requires the efficient development of loosely-coupled and interoperable sets of services. Existing design approaches do not always take full advantage of the value and importance of the engineering invested in existing legacy systems. This paper proposes an approach to define the key services from such legacy systems effectively. The approach focuses on identifying these services based on a Model-Driven Architecture approach supported by guidelines over a wide range of possible service types

Towards Peer-production in Public Services: cases from Finland

Drawing from a case-study on Helsinki Home Care, the authors identify institutional impacts of new service development in the context of public service delivery, posed by the increasingly collaborative nature of service development and delivery. The authors illustrate the change through identification of characteristics embedded in the traditional professional logic, and the new service logic. With this, the paper contributes to the theoretical discussion on service innovation and collaborative service creation, showing that solely the technical, organizational or commercial perspectives are insufficient in understanding the service development process. This paper further widens the discussion about public service innovation using the institutional change framework. There are many challenges and opportunities in designing, developing and maintaining services for participatory modes of governance, not to mention their co-creation and peer-to-peer aspects. We ask what can be learned from the current research, and what is happening already beyond academia? With the aim to increase the opportunities for dialogue between the Finnish scene and the international context, we have gathered this collection of articles that deal broadly with the relationships between peer-to-peer dynamics, and public services. Most of the cases presented are illustrative of recent developments and discussions in Finnish society, however, also included are broader international perspectives, giving historical reflection and future-oriented speculation on how peer production might affect the structures of our society

Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer

Comparative StudyMeta-AnalysisReviewValidation StudiesThis is the final version of the article. Available from Elsevier via the DOI in this record.OBJECTIVES: To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). STUDY DESIGN AND SETTING: We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman ρ, surrogate threshold effect (STE), and R(2) were also estimated across predefined trial-level covariates. RESULTS: We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman ρ ranged from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. CONCLUSION: None of the end points in this study were found to achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy

A rare cause of dyspepsia: a case report of gastric diverticulum

A gastric diverticulum is an outpouching from the gastric mucosa. It is extremely rare. It is normally asymptomatic, but some may present with non-specific abdominal pain. A combination of upper gastrointestinal endoscopy and radiological contrast study such as oral barium study and computed tomography are needed to make a definite diagnosis and to rule out other associated pathology. Although treatment with medical therapy has been reported to be effective, the use of open and laparoscopic resection also yields a good outcome in the management of complicated gastric diverticulum. We present a case of symptomatic gastric diverticulum which has been successfully treated with medical therapy

The shallow shelf approximation as a "sliding law" in a thermomechanically coupled ice sheet model

The shallow shelf approximation is a better ``sliding law'' for ice sheet modeling than those sliding laws in which basal velocity is a function of driving stress. The shallow shelf approximation as formulated by \emph{Schoof} [2006a] is well-suited to this use. Our new thermomechanically coupled sliding scheme is based on a plasticity assumption about the strength of the saturated till underlying the ice sheet in which the till yield stress is given by a Mohr-Coulomb formula using a modeled pore water pressure. Using this scheme, our prognostic whole ice sheet model has convincing ice streams. Driving stress is balanced in part by membrane stresses, the model is computable at high spatial resolution in parallel, it is stable with respect to parameter changes, and it produces surface velocities seen in actual ice streams.Comment: 12 pages of text; 4 tables; 27 figures; submitted to JGR Earth Surfac

Validation of surrogate endpoints in advanced solid tumors: systematic review of statistical methods, results, and implications for policy makers.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tReviewThis is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this record.OBJECTIVES: Licensing of, and coverage decisions on, new therapies should rely on evidence from patient-relevant endpoints such as overall survival (OS). Nevertheless, evidence from surrogate endpoints may also be useful, as it may not only expedite the regulatory approval of new therapies but also inform coverage decisions. It is, therefore, essential that candidate surrogate endpoints be properly validated. However, there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers. METHODS: We review current statistical approaches to surrogate-endpoint validation based on meta-analysis in various advanced-tumor settings. We assessed the suitability of two surrogates (progression-free survival [PFS] and time-to-progression [TTP]) using three current validation frameworks: Elston and Taylor's framework, the German Institute of Quality and Efficiency in Health Care's (IQWiG) framework and the Biomarker-Surrogacy Evaluation Schema (BSES3). RESULTS: A wide variety of statistical methods have been used to assess surrogacy. The strength of the association between the two surrogates and OS was generally low. The level of evidence (observation-level versus treatment-level) available varied considerably by cancer type, by evaluation tools and was not always consistent even within one specific cancer type. CONCLUSIONS: Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated. According to IQWiG's framework, only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents. Our study emphasizes the challenges of surrogate-endpoint validation and the importance of building consensus on the development of evaluation frameworks

Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer

In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel

Short- and long-term glucocorticoid treatment enhances insulin signalling in human subcutaneous adipose tissue

BACKGROUND: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's syndrome) is characterized by increased adiposity and insulin resistance. Although GCs cause global insulin resistance in vivo, we have previously shown that GCs are able to augment insulin action in human adipose tissue, contrasting with their action in skeletal muscle. Cushing's syndrome develops following chronic GC exposure and, in addition, is a state of hyperinsulinemia. OBJECTIVES: We have therefore compared the impact of short- (24 h) and long-term (7 days) GC administration on insulin signalling in differentiated human adipocytes in the presence of low or high concentrations of insulin. RESULTS: Both short- (24 h) and long-term (7 days) treatment of chub-s7 cells with dexamethasone (Dex) (0.5 μM) increased insulin-stimulated pTyr612IRS1 and pSer473akt/PKB, consistent with insulin sensitization. Chronic high-dose insulin treatment induced insulin resistance in chub-s7 cells. However, treatment with both high-dose insulin and Dex in combination still caused insulin sensitization. CONCLUSIONS: In this human subcutaneous adipocyte cell line, prolonged GC exposure, even in the presence of high insulin concentrations, is able to cause insulin sensitization. We suggest that this is an important mechanism driving adipogenesis and contributes to the obese phenotype of patients with Cushing's syndrome

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (>75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P<0.001). Using specific thresholds, patients with ⩾25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P<0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease