Report of the Horse Mackerel Exchange and Workshop 2006

Following a recommendation from PGCCDBS, a workshop on age calibration of horse mackerel was carried out. The workshop was preceded by an exchange. The objectives were: to improve the quality of horse mackerel readings by international calibration. In particular, attempt to resolve the observed differences between countries. Estimate the accuracy and precision of the age readings before and after the intercalibration. Take into account differences between areas and methods. Training of new horse mackerel readers

Dynamic tuneable G protein-coupled receptor monomer-dimer populations

G protein-coupled receptors (GPCRs) are the largest class of membrane receptors, playing a key role in the regulation of processes as varied as neurotransmission and immune response. Evidence for GPCR oligomerisation has been accumulating that challenges the idea that GPCRs function solely as monomeric receptors; however, GPCR oligomerisation remains controversial primarily due to the difficulties in comparing evidence from very different types of structural and dynamic data. Using a combination of single-molecule and ensemble FRET, double electron–electron resonance spectroscopy, and simulations, we show that dimerisation of the GPCR neurotensin receptor 1 is regulated by receptor density and is dynamically tuneable over the physiological range. We propose a “rolling dimer” interface model in which multiple dimer conformations co-exist and interconvert. These findings unite previous seemingly conflicting observations, provide a compelling mechanism for regulating receptor signalling, and act as a guide for future physiological studies

The additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress cardiac MRI for the detection of myocardial ischemia

Purpose of this study was to assess the additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress Cardiac-MR (CMR). Dobutamine Stress CMR was performed in 115 patients with an inconclusive diagnosis of myocardial ischemia on a 1.5 T system (Magnetom Avanto, Siemens Medical Systems). Three short-axis cine and grid series were acquired during rest and at increasing doses of dobutamine (maximum 40 μg/kg/min). On peak dose dobutamine followed immediately by a first pass myocardial perfusion imaging sequence. Images were graded according to the sixteen-segment model, on a four point scale. Ninety-seven patients showed no New (Induced) Wall Motion Abnormalities (NWMA). Perfusion imaging showed absence of perfusion deficits in 67 of these patients (69%). Perfusion deficits attributable to known previous myocardial infarction were found in 30 patients (31%). Eighteen patients had NWMA, indicative for myocardial ischemia, of which 14 (78%) could be confirmed by a corresponding perfusion deficit. Four patients (22%) with NWMA did not have perfusion deficits. In these four patients NWMA were caused by a Left Bundle Branch Block (LBBB). They were free from cardiac events during the follow-up period (median 13.5 months; range 6–20). Addition of first-pass myocardial perfusion imaging during peak-dose dobutamine stress CMR can help to decide whether a NWMA is caused by myocardial ischemia or is due to an (inducible) LBBB, hereby preventing a false positive wall motion interpretation

Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Diabetic Macular Edema (BRDME):The BRDME Study, a Randomized Trial

Purpose: To generate conclusive evidence regarding the noninferiority of intravitreal bevacizumab compared with ranibizumab in patients with diabetic macular edema (DME). Design: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. Participants: Eligible patients were older than 18 years, diagnosed with type 1 or type 2 diabetes mellitus, with glycosylated hemoglobin of less than 12%, central area thickness of more than 325 μm, and visual impairment from DME with a best-corrected visual acuity (BCVA) between 24 letters and 78 letters. Methods: From June 2012 through February 2018, a total of 170 participants were randomized to receive 6 monthly injections of either 1.25 mg bevacizumab (n = 86) or 0.5 mg ranibizumab (n = 84). Main Outcome Measures: Primary outcome was change in BCVA from baseline to month 6 compared between the 2 treatment arms. The noninferiority margin was 3.5 letters. Results: The difference in mean BCVA between treatment arms was 1.8 letters in favor of ranibizumab after 6 months of follow-up; BCVA improved by 4.9±6.7 letters in the bevacizumab group and 6.7±8.7 letters in the ranibizumab group. The lower bound of the 2-sided 90% confidence interval (CI) was –3.626 letters, exceeding the noninferiority margin of 3.5 letters. Central area thickness decreased more with ranibizumab (138.2±114.3 μm) compared with bevacizumab (64.2±104.2 μm). In a post hoc subgroup analysis, participants with a worse BCVA at baseline (≤69 letters) improved by 6.7±7.0 letters with bevacizumab and 10.4±10.0 letters with ranibizumab, and central area thickness decreased significantly more in the ranibizumab arm of this subgroup compared with the bevacizumab arm. Participants with an initially better BCVA at baseline (≥70 letters) did not demonstrate differences in BCVA or OCT outcomes between treatment arms. Conclusions: Based on change in BCVA from baseline to month 6, the noninferiority of 1.25 mg bevacizumab to 0.5 mg ranibizumab was not confirmed. Only the subgroup of patients with a lower BCVA at baseline showed better visual acuity and anatomic outcomes with ranibizumab. Our study confirmed the potential differential efficacy of anti–vascular endothelial growth factor agents in the treatment of DME as well as the difference in response between patient groups with different baseline visual acuities

Enhancing modeling and change support for process families through change patterns

The increasing adoption of process-aware information systems (PAISs), together with the variability of business processes (BPs), has resulted in large collections of related process model variants (i.e., process families). To effectively deal with process families, several proposals (e.g., C-EPC, Provop) exist that extend BP modeling languages with variability-specific constructs. While fostering reuse and reducing modeling efforts, respective constructs imply additional complexity and demand proper support for process designers when creating and modifying process families. Recently, generic and language independent adaptation patterns were successfully introduced for creating and evolving single BP models. However, they are not sufficient to cope with the specific needs for modeling and evolving process families. This paper suggests a complementary set of generic and language-independent change patterns specifically tailored to the needs of process families. When used in combination with existing adaptation patterns, change patterns for process families will enable the modeling and evolution of process families at a high-level of abstraction. Further, they will serve as reference for implementing tools or comparing proposals managing process families. © 2013 Springer-Verlag.This work has been developed with the support of MICINN under the Project EVERYWARE TIN2010-18011.Ayora Esteras, C.; Torres Bosch, MV.; Weber, B.; Reichert, M.; Pelechano Ferragud, V. (2013). Enhancing modeling and change support for process families through change patterns. En Enterprise, Business-Process and Information Systems Modeling, BPMDS 2013. Springer Verlag. 246-260. https://doi.org/10.1007/978-3-642-38484-4_18S246260van der Aalst, W.M.P., ter Hofstede, A.H.M., Barros, B.: Workflow Patterns. Distributed and Parallel Databases 14(1), 5–51 (2003)Aghakasiri, Z., Mirian-Hosseinabadi, S.H.: Workflow change patterns: Opportunities for extension and reuse. In: Proc. SERA 2009, pp. 265–275 (2009)Ayora, C., Torres, V., Reichert, M., Weber, B., Pelechano, V.: Towards run-time flexibility for process families: Open issues and research challenges. In: La Rosa, M., Soffer, P. (eds.) BPM 2012 Workshops. LNBIP, vol. 132, pp. 477–488. Springer, Heidelberg (2013)Ayora, C., Torres, V., Weber, B., Reichert, M., Pelechano, V.: Change patterns for process families. Technical Report, PROS-TR-2012-06, http://www.pros.upv.es/technicalreports/PROS-TR-2012-06.pdfDadam, P., Reichert, M.: The ADEPT project: a decade of research and development for robust and flexible process support. Com. Sci. - R&D 23, 81–97 (2009)Dijkman, R., La Rosa, M., Reijers, H.A.: Managing large collections of business process models - Current techniques and challenges. Comp. in Ind. 63(2), 91–97 (2012)Döhring, M., Zimmermann, B., Karg, L.: Flexible workflows at design- and runtime using BPMN2 adaptation patterns. In: Abramowicz, W. (ed.) BIS 2011. LNBIP, vol. 87, pp. 25–36. Springer, Heidelberg (2011)Gottschalk, F.: Configurable process models. Ph.D. thesis, Eindhoven University of Technology, The Netherlands (2009)Grambow, G., Oberhauser, R., Reichert, M.: Contextual injection of quality measures into software engineering processes. Intl. J. Adv. in Software 4, 76–99 (2011)Gschwind, T., Koehler, J., Wong, J.: Applying patterns during business process modeling. In: Dumas, M., Reichert, M., Shan, M.-C. (eds.) BPM 2008. LNCS, vol. 5240, pp. 4–19. Springer, Heidelberg (2008)Günther, C.W., Rinderle, S., Reichert, M., van der Aalst, W.M.P.: Change mining in adaptive process management systems. In: Meersman, R., Tari, Z. (eds.) OTM 2006. LNCS, vol. 4275, pp. 309–326. Springer, Heidelberg (2006)Hallerbach, A., Bauer, T., Reichert, M.: Context-based configuration of process variants. In: Proc. TCoB 2008, pp. 31–40 (2008)Hallerbach, A., Bauer, T., Reichert, M.: Capturing variability in business process models: the Provop approach. J. of Software Maintenance 22(6-7), 519–546 (2010)Kitchenham, B., Charters, S.: Guidelines for performing Systematic Literature Reviews in Software Engineering, Technical Report EBSE/EPIC–2007–01 (2007)Kulkarni, V., Barat, S., Roychoudhury, S.: Towards business application product lines. In: France, R.B., Kazmeier, J., Breu, R., Atkinson, C. (eds.) MODELS 2012. LNCS, vol. 7590, pp. 285–301. Springer, Heidelberg (2012)Küster, J.M., Gerth, C., Förster, A., Engels, G.: Detecting and resolving process model differences in the absence of a change log. In: Dumas, M., Reichert, M., Shan, M.-C. (eds.) BPM 2008. LNCS, vol. 5240, pp. 244–260. Springer, Heidelberg (2008)Küster, J.M., Gerth, C., Engels, G.: Dynamic computation of change operations in version management of business process models. In: Kühne, T., Selic, B., Gervais, M.-P., Terrier, F. (eds.) ECMFA 2010. LNCS, vol. 6138, pp. 201–216. 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In: Dustdar, S., Fiadeiro, J.L., Sheth, A.P. (eds.) BPM 2006. LNCS, vol. 4102, pp. 368–377. Springer, Heidelberg (2006)Reichert, M., Weber, B.: Enabling flexibility in process-aware information systems: challenges, methods, technologies. Springer (2012)Reinhartz-Berger, I., Soffer, P., Sturm, A.: Organizational reference models: supporting an adequate design of local business processes. IBPIM 4(2), 134–149 (2009)Rosemann, M., van der Aalst, W.M.P.: A configurable reference modeling language. Information Systems 32(1), 1–23 (2007)Russell, N., ter Hofstede, A.H.M., Edmond, D., van der Aalst, W.M.P.: Workflow data patterns. Technical Report FIT-TR-2004-01, Queensland Univ. of Technology (2004)Russell, N., ter Hofstede, A.H.M., Edmond, D., van der Aalst, W.M.P.: Workflow resource patterns. Technical Report WP 127, Eindhoven Univ. of Technology (2004)Russell, N., van der Aalst, W.M.P., ter Hofstede, A.H.M.: Workflow Exception Patterns. In: Martinez, F.H., Pohl, K. (eds.) CAiSE 2006. 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Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Retinal Vein Occlusion:The Bevacizumab to Ranibizumab in Retinal Vein Occlusions (BRVO) study, a Randomized Trial

PURPOSE: Comparing the efficacy of intravitreal injections of bevacizumab to ranibizumab in the treatment of macular edema (ME) resulting from retinal vein occlusion (RVO). DESIGN: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. The noninferiority margin was 4 letters. PARTICIPANTS: Patients with vision loss resulting from ME secondary to a branch or (hemi) central RVO who might benefit from anti-vascular endothelial growth factor treatment were eligible for participation. METHODS: From June 2012 through February 2018, 277 participants were randomized to receive injections of 1.25 mg bevacizumab (n = 139) or 0.5 mg ranibizumab (n = 138). The follow-up was 6 months with a monthly dosing interval. MAIN OUTCOME MEASURES: The primary outcome was a change in visual acuity from baseline at 6 months. Changes in the central area thickness and safety were studied as secondary outcomes. RESULTS: The mean visual acuity (±standard deviation) improved, with 15.3±13.0 letters for bevacizumab and 15.5±13.3 letters for ranibizumab after 6 months of monthly treatment. The lower limit of the 2-sided 90% confidence interval was -1.724 letters, which is within the noninferiority margin of 4 letters. Even in the branch and (hemi-)central RVO subgroups, minimal differences were found in visual acuity outcomes between treatment arms. Changes in central area thickness on OCT at 6 months did not differ significantly between treatment groups, with a decrease of 287.0±231.3 μm in the bevacizumab group and 300.8±224.8 μm in the ranibizumab group. Severe adverse events (SAEs) were also distributed equally over both treatment groups: 10 participants (7.1%) in the bevacizumab group and 13 participants (9.2%) in the ranibizumab group experienced SAEs. CONCLUSIONS: This study showed, based on the change in visual acuity, that bevacizumab is noninferior to ranibizumab for patients with ME resulting from RVO of either subtype when receiving monthly injections for a period of 6 months. In addition, anatomic and safety outcomes did not differ between treatment groups. Based on our findings, bevacizumab may be an effective alternative to ranibizumab

Automatic business process model extension to repair constraint violations

Consider an artifact-centric business process model, containing both a data model and a process model. When executing the process, it may happen that some of the data constraints from the data model are violated. Bearing this in mind, we propose an approach to automatically generate an extension to the original business process model that, when executed after a constraint violation, repairs the contents of the data leaving it in a new consistent state.Peer ReviewedPostprint (author's final draft

Performance of adenosine “stress-only” perfusion MRI in patients without a history of myocardial infarction: a clinical outcome study

To assess the diagnostic value of adenosine “stress-only” myocardial perfusion MR for ischemia detection as an indicator for coronary angiography in patients without a prior myocardial infarction and a necessity to exclude ischemia. Adenosine perfusion MRI was performed at 1.5 T in 139 patients with a suspicion of ischemia and no prior myocardial infarction. After 3 min of adenosine infusion a perfusion sequence was started. Patients with a perfusion defect were referred to coronary angiography (CAG). Patients with a normal perfusion were enrolled in follow-up. Fourteen out of 139 patients (10.1%) had a perfusion defect indicative of ischemia. These patients underwent a coronary angiogram, which showed complete agreement with the perfusion images. 125 patients with a normal myocardial perfusion entered follow-up (median 672 days, range 333–1287 days). In the first year of follow-up one Major Adverse Coronary Event (MACE) occurred and one patient had new onset chest pain with a confirmed coronary stenosis. Reaching a negative predictive value for MACE of 99.2% and for any coronary event of 98.4%. At 2 year follow-up no additional MACE occurred. Sensitivity of adenosine perfusion MR for MACE is 93.3% and specificity and positive predictive value are 100%. Adenosine myocardial perfusion MR for the detection of myocardial ischemia in a “stress-only” protocol in patients without prior myocardial infarctions, has a high diagnostic accuracy. This fast examination can play an important role in the evaluation of patients without prior myocardial infarctions and a necessity to exclude ischemia

A Qualitative Evaluation of IoT-driven eHealth: Knowledge Management, Business Models and Opportunities, Deployment and Evolution

eHealth has a major potential, and its adoption may be considered necessary to achieve increased ambulant and remote medical care, increased quality, reduced personnel needs, and reduced costs potential in healthcare. In this paper the authors try to give a reasonable, qualitative evaluation of IoT-driven eHealth from theoretical and practical viewpoints. They look at associated knowledge management issues and contributions of IoT to eHealth, along with requirements, benefits, limitations and entry barriers. Important attention is given to security and privacy issues. Finally, the conditions for business plans and accompanying value chains are realistically analyzed. The resulting implementation issues and required commitments are also discussed based on a case study analysis. The authors confirm that IoT-driven eHealth can happen and will happen; however, much more needs to be addressed to bring it back in sync with medical and general technological developments in an industrial state-of-the-art perspective and to get recognized and get timely the benefits