Validating design principles for creative collaboration

Design Science Research (DSR) lacks accepted validation approaches to validate its outcomes (design principles and design solutions). The quality of such a validation has to be ensured so that the outcomes of DSR are as methodologically thorough and as practically relevant as possible. This study introduces a pragmatic validation approach to ensure the quality of design principles. It uses a three-step approach, combining (1) evaluating the design solution as a case in practice, (2) qualifying the implementation of the set of design principles, and (3) assessing the validity of evaluation and qualification results. The validation approach is illustrated by assessing the evaluation results of a creativity facilitation course (design solution) developed according to a set of design principles

The Quest for a Leaner, Not a Meaner Government

In 1993, the Clinton administration launched the National Performance Review [NPR], a large-scale effort to create a more entrepreneurial government that ?works better and costs less?. The NPR relied heavily on the input and effort of federal civil servants. Although the rationale for the reduction was formulated in terms of performance improvement, it was as much driven by the goal of cost cutting. A similar effort took place in The Netherlands with the ?Grote Efficiency Operatie? [Operation Efficiency]. During the 1980?s, the Dutch government established six so-called ?major operations? to improve its performance and reduce costs. The history, targets, procedure and organization as well as results of both countries? efforts are analyzed. Comparison of the NPR and the GEO entails certain risks but yields insights that contribute to an understanding of efforts at public sector reform which transcends particular national contexts. Both operations began as efforts to improve efficiency but quickly became focused on personnel reduction

Indirect costs of disease; an international comparison

Results of economic evaluations are often strongly influenced by estimates of indirect costs. International comparability of these estimates may contribute to rational decision-making in health care policy. Hence, estimates should be international comparable. Comparability of these results between countries may be hampered due to variation in methodology, data sources, valuation of production losses, and social security arrangements. Furthermore differences in epidemiology, demography and economic environment may cause variation in the level and the distribution by diagnosis of indirect costs. In this study indirect costs of disease for the Netherlands are compared with estimates for Sweden and the United States. We found large differences: both in the share of indirect costs in GDP as in the constituting elements, absence from work, disability and mortality. The level of indirect costs due to absence from work and the distribution according to diagnosis are quite similar for the two European countries. The costs of disability are particularly high for the Netherlands. Comparison of disability costs between the three countries is hampered due to lack of quantitative information on the influence of social insurance arrangements on the level of indirect costs and the distribution by diagnosis. The large number of deaths at young age in the U.S. is responsible for the higher mortality costs compared to the two European countries

Anatomical parameters for musculoskeletal modeling of the hand and wrist

International audienceA musculoskeletal model of the hand and wrist can provide valuable biomechanical and neurophysiological insights, relevant for clinicians and ergonomists. Currently, no consistent data-set exists comprising the full anatomy of these upper extremity parts. The aim of this study was to collect a complete anatomical data-set of the hand and wrist, including the intrinsic and extrinsic muscles. One right lower arm, taken from a fresh frozen female specimen, was studied. Geometrical data for muscles and joints were digitized using a 3D optical tracking system. For each muscle, optimal fiber length and physiological cross-sectional area were assessed based on muscle belly mass, fiber length, and sarcomere length. A brief description of model, in which these data were imported as input, is also provided. Anatomical data including muscle morphology and joint axes (48 muscles and 24 joints) and mechanical representations of the hand are presented. After incorporating anatomical data in the presented model, a good consistency was found between outcomes of the model and the previous experimental studies

On the IMF's Revised Classification of Exchange Rate Arrangements

This study compares the health care costs of The Netherlands with the United States and Sweden and estimates the impact of demographic change on costs. Total health care costs were allocated to disease, age, sex and specific subsectors. For The Netherlands 75% of the costs in 1988 were assigned to specific diseases. Costs of mental disorders and other chronic non-fatal diseases dominate, followed by cardiovascular diseases. The effect of age is strong from age 70 years onwards. The effect of sex, adjusting for age, is small, except for elderly women, who are more expensive. Both total and disease-specific costs are similar in The Netherlands and Sweden, but differ from those in the US. The available data suggest that the differences in medical practice and health care systems may explain a substantial part of the divergent results; demographic or epidemiologic aspects seem less important. Ageing induces, in the Dutch case, a modest 0.7% annual increase in costs. The contribution of other forces in the increase of costs is probably more important. A structural upward pressure on costs also prevails in The Netherlan

Effect of statins on mitochondrial function and contractile force in human skeletal and cardiac muscle

Objectives and Background: The success of statin therapy in reducing cardiovascular morbidity and mortality is contrasted by the skeletal muscle complaints, which often leads to nonadherence. Previous studies have shown that inhibition of mitochondrial function plays a key role in statin intolerance. Recently, it was found that statins may also influence energy metabolism in cardiomyocytes. This study assessed the effects of statin use on cardiac muscle ex vivo from patients using atorvastatin, rosuvastatin, simvastatin or pravastatin and controls. Methods: Cardiac tissue and skeletal muscle tissue were harvested during open heart surgery after patients provided written informed consent. Patients included were undergoing cardiac surgery and either taking statins (atorvastatin, rosuvastatin, simvastatin or pravastatin) or without statin therapy (controls). Contractile behaviour of cardiac auricles was tested in an ex vivo set-up and cellular respiration of both cardiac and skeletal muscle tissue samples was measured using an Oxygraph-2k. Finally, statin acid and lactone concentrations were quantified in cardiac and skeletal homogenates by LC-MS/MS. Results: Fatty acid oxidation and mitochondrial complex I and II activity were reduced in cardiac muscle, while contractile function remained unaffected. Inhibition of mitochondrial complex III by statins, as previously described, was confirmed in skeletal muscle when compared to control samples, but not observed in cardiac tissue. Statin concentrations determined in skeletal muscle tissue and cardiac muscle tissue were comparable. Conclusions: Statins reduce skeletal and cardiac muscle cell respiration without significantly affecting cardiac contractility

Diffusion-Weighted MRI for Selection of Complete Responders After Chemoradiation for Locally Advanced Rectal Cancer: A Multicenter Study

PURPOSE: In 10-24% of patients with rectal cancer who are treated with neoadjuvant chemoradiation, no residual tumor is found after surgery (ypT0). When accurately selected, these complete responders might be considered for less invasive treatments instead of standard surgery. So far, no imaging method has proven reliable. This study was designed to assess the accuracy of diffusion-weighted MRI (DWI) in addition to standard rectal MRI for selection of complete responders after chemoradiation. METHODS: A total of 120 patients with locally advanced rectal cancer from three university hospitals underwent chemoradiation followed by a restaging MRI (1.5T), consisting of standard T2W-MRI and DWI (b0-1000). Three independent readers first scored the standard MRI only for the likelihood of a complete response using a 5-point confidence score, after which the DWI images were added and the scoring was repeated. Histology (ypT0 vs. ypT1-4) was the standard reference. Diagnostic performance for selection of complete responders and interobserver agreement were compared for the two readings. RESULTS: Twenty-five of 120 patients had a complete response (ypT0). Areas under the ROC-curve for the three readers improved from 0.76, 0.68, and 0.58, using only standard MRI, to 0.8, 0.8, and 0.78 after addition of DWI (P = 0.39, 0.02, and 0.002). Sensitivity for selection of complete responders ranged from 0-40% on standard MRI versus 52-64% after addition of DWI. Specificity was equally high (89-98%) for both reading sessions. Interobserver agreement improved from kappa 0.2-0.32 on standard MRI to 0.51-0.55 after addition of DWI. CONCLUSIONS: Addition of DWI to standard rectal MRI improves the selection of complete responders after chemoradiation

Value of ADC measurements for nodal staging after chemoradiation in locally advanced rectal cancer—a per lesion validation study

OBJECTIVES: To evaluate the performance of diffusion-weighted MRI (DWI) in addition to T2-weighted (T2W) MRI for nodal restaging after chemoradiation in rectal cancer. METHODS: Thirty patients underwent chemoradiation followed by MRI (1.5 T) and surgery. Imaging consisted of T2W-MRI and DWI (b0, 500, 1000). On T2W-MRI, nodes were scored as benign/malignant by two independent readers (R1, R2). Mean apparent diffusion coefficient (ADC) was measured for each node. Diagnostic performance was compared for T2W-MRI, ADC and T2W+ADC, using a per lesion histological validation. RESULTS: ADC was higher for the malignant nodes (1.43 +/- 0.38 vs 1.19 +/- 0.27 *10(-3) mm(2)/s, p < 0.001). Area under the ROC curve/sensitivity/specificity were 0.88/65%/93% (R1) and 0.95/71%/91% (R2) using T2W-MRI; 0.66/53%/82% using ADC (mean of two readers); and 0.91/56%/98% (R1) and 0.96/56%/99% (R2) using T2W+ADC. There was no significant difference between T2W-MRI and T2W+ADC. Interobserver reproducibility was good for T2W-MRI (kappa0.73) and ADC (intraclass correlation coefficient 0.77). CONCLUSIONS: After chemoradiation, ADC measurements may have potential for nodal characterisation, but DWI on its own is not reliable. Addition of DWI to T2W-MRI does not improve accuracy and T2W-MRI is already sufficiently accurate

A Human Minor Histocompatibility Antigen Specific for B Cell Acute Lymphoblastic Leukemia

Human minor histocompatibility antigens (mHags) play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). As most mHags are not leukemia specific but are also expressed by normal tissues, antileukemia reactivity is often associated with life-threatening graft-versus-host disease (GVHD). Here, we describe a novel mHag, HB-1, that elicits donor-derived CTL reactivity in a B cell acute lymphoblastic leukemia (B-ALL) patient treated by HLA-matched BMT. We identified the gene encoding the antigenic peptide recognized by HB-1–specific CTLs. Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus–transformed B cells. The HB-1 gene–encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene generates a single amino acid exchange from His to Tyr at position 8 within this peptide. This amino acid substitution is critical for recognition by HB-1–specific CTLs. The restricted expression of the polymorphic HB-1 Ag by B-ALL cells and the ability to generate HB-1–specific CTLs in vitro using peptide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD