Transforming Existing Procedural Business Processes into a Constraint-Based Formalism

Many organizations use business process management to manage and model their processes. Currently, flow-based process formalisms, such as BPMN, are considered the standard for modeling processes. However, recent literature describes several limitations of this type of formalism that can be solved by adopting a constraint-based formalism. To preserve economic investments in existing process models, transformation activities needed to be limited. This paper presents a methodical approach for performing the tedious parts of process model transformation. Executing the method results in correctly transformed process models and reduces the effort required for converting the process models

The Uptake and Impact of a Personal Health Record for Patients with Type 2 Diabetes Mellitus in Primary Care: a research protocol for a backward and forward evaluation

A Personal Health Record (PHR) is a promising technology for improving the quality of chronic disease management. Despite the efforts that have been made in a research project to develop a PHR for patients with type 2 diabetes mellitus in primary care (e-Vita), differences have been reported between the number of registered users in the participating primary practices. To gain insight into the factors that influence the implementation of the PHR into daily health care processes and into the possibilities to improve the content, interviews have been conducted with participating primary practice nurses and other stakeholders in the research project. A first impression of the interviews indicated that in many cases, the low impact of the PHR is due to a lack of information about the purpose, content and use of the syste

Gene therapy for insulin dependent diabetes mellitus using IL-12p40- producing islet grafts

本研究では, インスリン依存型糖尿病 (IDDM) のモデル動物である NOD (nonobese diabetic) マウスに, 抑制性サイトカイン遺伝子をアデノウイルスベクターを用いて導入した膵ラ島移植を行ない自己免疫機序による拒絶反応の阻止を試みた。糖尿病発症NODマウスに, IL-12p40およびIL-10遺伝子をアデノウイルスベクターを用いて導入したNODマウス膵ラ島を移植した。IL-12p40産生膵ラ島移植では4週間以上の移植片の生着を認めたが, IL-10産生膵ラ島移植では移植片の長期の生着は得られなかった。組織学的検討では, IL-12p40産生膵ラ島移植では移植7日および60日後で正常膵ラ島構造を維持し軽度の単核球浸潤のみ認めたが, IL-10産生膵ラ島移植では移植7日後ですでに著明な単核球浸潤を伴い膵ラ島構造も破壊されていた。また, RT-PCR法での移植片局所のサイトカインの解析より, 移植片の長期生着のメカニズムとして, IL-12p40産生膵ラ島移植ではIFN-γ産生細胞の減少とTGF-β産生細胞の誘導により免疫寛容が成立した可能性が示唆された。以上より, IL-12p40産生膵ラ島移植では移植片の長期生着が可能であり, 今後のIDDM発症後の治療法として膵ラ島移植を用いた遺伝子療法の確立への第一歩と考えられた。 / Insulin dependent diabetes mellitus (IDDM) is considered to be a T cell-mediated autoimmune disease. It has been demonstrated that T helper (Th) 1 cells would play an important role in destruction of pancreatic β cells. It has recently been reported that systemic administration of IL-12 accelerates diabetes onset and that IL-12p40, an antagonist of IL-12, prevents diabetes development. From these results, we considered to establish gene therapy for IDDM with the islet grafts producing immunosuppressive cytokine such as IL-12p40. The syngeneic islet transplantation into diabetic nonobese diabetic (NOD) mice was performed using the recombinant adenoviral vector with inserted mlL-12p40 (Ad. IL-12p40) or mlL-10 (Ad. IL-10). Ad. IL-12p40-transfected islet grafts could significantly prevent autoimmune diabetes recurrence for over 4wk after transplantation (Tx). In contrast, Ad.IL-10 could not prolong syngeneic islet graft survival. Histological study revealed that IL-12p40-producing islet grafts remained normal in configulation with a small amount of lymphoid infiltration on day 60 after Tx, in contrast to IL-10-producing islet grafts with massive infiltration on day 7 after Tx. Reverse transcription (RT)-PCR analysis demonstrated that IL-12p40 gene transfer into islet grafts led to the significant decrease of IFN- 7 and the augmentation of TGF-β. These results suggest that IL-12 plays a key role in the autoimmune diabetes and that locally-produced IL-12p40 protects syngeneic islet grafts from recurrent autoimmune destruction of β cells by reducing IFN- γ and increasing TGF-β. This novel gene therapy would be clinically applicable to human IDDM

Big Data for personalized healthcare

Big Data, often defined according to the 5V model (volume, velocity, variety, veracity and value), is seen as the key towards personalized healthcare. However, it also confronts us with new technological and ethical challenges that require more sophisticated data management tools and data analysis techniques. This vision paper aims to better understand the technological and ethical challenges we face when using and managing Big Data in healthcare as well as the way in which it impacts our way of working, our health, and our wellbeing. A mixed-methods approach (including a focus group, interviews, and an analysis of social media) was used to gain a broader picture about the pros and cons of using Big Data for personalized healthcare from three different perspectives: Big Data experts, healthcare workers, and the online public. All groups acknowledge the positive aspects of applying Big Data in healthcare, touching upon a wide array of issues, both scientifically and socially. By sharing health data, value can be created that goes beyond the individual patient. The Big Data revolution in healthcare is seen as a promising and innovative development. Yet potential facilitators and barriers need to be faced first to reach its full potential. Concerns were raised about privacy, trust, reliability, safety, purpose limitation, liability, profiling, data ownership, and loss of autonomy. Also, the importance of adding the people-centered view to the rather data-centered 5V model is stressed, in order to get a grip on the opportunities for using Big Data in personalized healthcare. People should be aware that the development of Big Data advancements is not self-evident

Open Archief

Het Nieuwe Instituut en het Nederlands Instituut voor Beeld en Geluid werkten in het project Open Archief samen om het creatief hergebruik van digitale erfgoedcollecties te stimuleren. Ze nodigden begin 2019 drie makers uit om op basis van de open collecties een nieuw autonoom mediawerk te ontwikkelen. Het beschikbaar stellen en artistiek hergebruiken van digitaal erfgoed stond daarbij centraal, met ruimte voor uiteenlopende creatieve, technische en auteursrechtelijke interpretaties. Een wederkerig experiment tussen instituten en makers. In deze digitale publicatie blikken de deelnemende makers en beide instituten terug op het project en delen de opgedane kennis en ervaringen met collega instellingen en makers

Moral reasoning perspectives of community pharmacists in situations of drug shortages

BACKGROUND: Drug shortages affect health systems worldwide. Research in community pharmacy has focused on the nature, extent and impact of these shortages on patients and pharmacists. However, pharmacists' moral reasoning in situations of drug shortages has not been addressed. OBJECTIVE: To explore the moral reasoning perspectives of Dutch community pharmacists in situations of drug shortages. METHOD: An electronic survey was developed around three drug shortage scenarios with a varying impact on patient outcomes: a Contraceptive, a Parkinson's and an Osteoporosis scenario. Pharmacists rated the likelihood of nine handling options and rated and ranked 13 considerations that may have played a role therein. The considerations represented three moral reasoning perspectives (MRPs): a business orientation (BO), a rules and regulations (RR), and a professional ethics (PE) MRP. Principle component analysis (PCA) was used to investigate construct validity of the MRPs. MRP rating and MRP ranking scores measured the relative importance of the different MRPs of pharmacists in the three shortages. RESULTS: Results from 267 Pharmacists were obtained. They reported mostly similar handling in the three shortages, except for the likelihood to make agreements with prescribers or other pharmacists and regarding the decision to import a product. The PCA analysis confirmed the three MRPs that accounted for 29% of variance in the data. Both the MRP rating and especially the MRP ranking scores indicated that PE-MRP considerations were most influential on pharmacists' intended handling of the shortages. In the Contraceptive and the Osteoporosis scenarios, the relative importance of a BO-MRP was higher than in the Parkinson's scenario. CONCLUSION: Pharmacists predominantly reason with a PE-MRP when handling drug shortages. However, this perspective can be compromised when the drug shortage is perceived to have a lower impact on patient outcomes and when alternative drugs or therapy are expensive

Assessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy

Altered vitamin B6 metabolism due to pathogenic variants in the gene PNPO causes early onset epileptic encephalopathy, which can be treated with high doses of vitamin B6. We recently reported that single nucleotide polymorphisms (SNPs) that influence PNPO expression in the brain are associated with genetic generalized epilepsy (GGE). However, it is not known whether any of these GGE-associated SNPs influence vitamin B6 metabolite levels. Such an influence would suggest that vitamin B6 could play a role in GGE therapy. Here, we performed genome-wide association studies (GWAS) to assess the influence of GGE associated genetic variants on measures of vitamin B6 metabolism in blood plasma in 2232 healthy individuals. We also asked if SNPs that influence vitamin B6 were associated with GGE in 3122 affected individuals and 20,244 controls. Our GWAS of vitamin B6 metabolites reproduced a previous association and found a novel genome-wide significant locus. The SNPs in these loci were not associated with GGE. We found that 84 GGE-associated SNPs influence expression levels of PNPO in the brain as well as in blood. However, these SNPs were not associated with vitamin B6 metabolism in plasma. By leveraging polygenic risk scoring (PRS), we found suggestive evidence of higher catabolism and lower levels of the active and transport forms of vitamin B6 in GGE, although these findings require further replication.Peer reviewe