Specification of freeform features

Freeform feature modeling is an extension to feature mod-eling in which, in addition to regular-shaped features, also freeform features are possible. Due to the large variety of freeform features, a generic approach to specify such fea-tures is required. This paper describes such an approach. A freeform feature class is specied by using a prototype and constraints. The latter are used to dene intuitive parame-ters and validity conditions for the class. A new, prototype-driven constraint solving method is used to unambiguously determine a freeform feature during the specication both of a class and of an instance to be added to a model. The speci cation of freeform features and the prototype-driven constraint solving method are discussed. Several examples are given

Web-based collaborative feature modeling

Collaborative modeling systems are distributed multiple-user sys-tems that are both concurrent and synchronized, aimed at sup-porting engineering teams in coordinating their modeling activi-ties. Instead of an iterative process, asynchronously sending prod

Cost-effectiveness of counseling and pedometer use to increase physical activity in the Netherlands: a modeling study

Background: Counseling in combination with pedometer use has proven to be effective in increasing physical activity and improving health outcomes. We investigated the cost-effectiveness of this intervention targeted at one million insufficiently active adults who visit their general practitioner in the Netherlands.Methods: We used the RIVM chronic disease model to estimate the long-term effects of increased physical activity on the future health care costs and quality adjusted life years (QALY) gained, from a health care perspective.Results: The intervention resulted in almost 6000 people shifting to more favorable physical-activity levels, and in 5100 life years and 6100 QALYs gained, at an additional total cost of EUR 67.6 million. The incremental cost-effectiveness ratio (ICER) was EUR 13,200 per life year gained and EUR 11,100 per QALY gained. The intervention has a probability of 0.66 to be cost-effective if a QALY gained is valued at the Dutch informal threshold for cost-effectiveness of preventive intervention of EUR 20,000. A sensitivity analysis showed substantial uncertainty of ICER values.Conclusion: Counseling in combination with pedometer use aiming to increase physical activity may be a cost-effective intervention. However, the intervention only yields relatively small health benefits in the Netherlands

The polypill in the primary prevention of cardiovascular disease: cost-effectiveness in the Dutch population

OBJECTIVES: The aim of the present study was to estimate the cost-effectiveness of the polypill in the primary prevention of cardiovascular disease. DESIGN: A health economic modeling study. SETTING: Primary health care in the Netherlands. PARTICIPANTS: Simulated individuals from the general Dutch population, aged 45-75 years of age. INTERVENTIONS: Opportunistic screening followed by prescription of the polypill to eligible individuals. Eligibility was defined as having a minimum 10-year risk of cardiovascular death as assessed with the SCORE function of alternatively 5%, 7.5%, or 10%. Different versions of the polypill were considered, depending on composition: 1) the Indian polycap, with three different types of blood pressure lowering drugs, a statin, and aspirin; 2) as 1) but without aspirin; 3) as 2) but with a double statin dose. In addition, a scenario of (targeted) separate antihypertensive and/or statin medication was simulated. PRIMARY OUTCOME MEASURES: Cases of acute myocardial infarction or stroke prevented, QALYs gained, and the costs per QALY gained. All interventions were compared with usual care. RESULTS: All scenarios were cost-effective with an incremental cost-effectiveness ratio between €7,900-12,300 per QALY compared with usual care. Most health gains were achieved with the polypill without aspirin and containing a double dose of statins. With a 10-year risk of 7.5% as threshold, this pill would prevent approximately 3.5% of all cardiovascular events. CONCLUSIONS: Opportunistic screening based on global cardiovascular risk assessment followed by polypill prescription to those with increased risk offers a cost-effective strategy. Most health gain is achieved by the polypill without aspirin and a double statin dose

Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma

Summary: The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma. : Using peptide phosphorylation profiling, Zomerman et al. identify two medulloblastoma phosphoprotein-signaling profiles that have prognostic value and are potentially targetable. They find that these profiles extend across transcriptome-based subgroup borders. This suggests that diverse genetic information converges on common protein-signaling pathways and highlights protein-signaling as a unique information layer. Keywords: medulloblastoma, protein-signaling, protein synthesis, MYC, TP53, proteome, phosphoproteom

¹⁸F-Fludeoxyglucose-Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer:A Multicenter Prospective Dutch Cohort Study (PLASTIC)

Importance: The optimal staging for gastric cancer remains a matter of debate. Objective: To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. Design, Setting, and Participants: This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. Exposures: All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. Main Outcomes and Measures: The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. Results: Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. Conclusions and Relevance: This study's findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Collaborative modeling with features

Collaborative systems are distributed multiple-user systems that are both concurrent and synchronized. An interesting research challenge is to develop a collaborative modeling system that offers all facilities of advanced modeling systems to its users, while at the same time providing them with the necessary coordination mechanisms that guarantee an effective collaboration. To achieve this, a web-based collaborative feature modeling system, webSPIFF, has been developed. It has a client-server architecture, with an advanced feature modeling system as a basis for the server, providing feature validation, multiple views and sophisticated visualization facilities. A good distribution of the functionality between the server and the clients has resulted in a well-balanced system. On the one hand, the server offers all the functionality of the original feature modeling system. On the other hand, all desirable interactive modeling functionality is offered by the clients, ranging from display of sophisticated feature model images to interactive model specification facilities. The architecture of webSPIFF, the distribution of model data, the functionality of the server and the clients, and the communication mechanisms are described. It is shown that a good compromise between interactivity and network load has been achieved, and that indeed advanced modeling with a collaborative system is feasible. 1

DETC2004-57695 CONSTRUCTION OF FREEFORM FEATURE MODELS WITH ATTACHMENTS

In freeform feature modeling, the shape domain of current feature modeling systems is extended with freeform shapes. A challenging task in this context is to develop a method for constructing a feature model in an intuitive, yet unambiguous manner, comparable to the construction methods for regularshaped feature models. This paper describes a framework in which it is possible to attach a face of a new freeform, volumetric feature instance to a face of a feature instance already in the model. In this framework, features are represented by configurations of freeform definition points, from which the shape is generated. By using geometric constraints on these definition points and other geometric entities within the model, freeform attachments can be realized. Apparent problems that emerge in this context are positioning of the new feature instance on the freeform attach face, fitting the geometry of the new feature instance to the existing model geometry, and maintenance of valid feature model geometry. The framework accommodates for these issues. Two types of attachment, for a freeform extrusion feature respectively a freeform wrap feature, are elaborated. With the attachments presented here, freeform feature models can be constructed in a fully parametrized, constraint-based way, just like regular-shaped feature models