Simon's Model Research Articles

Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial

No randomised controlled trial has ever been done in patients with metastatic phaeochromocytomas and paragangliomas. Preclinical and first clinical evidence suggested beneficial effects of sunitinib. We aimed to evaluate the safety and efficacy of sunitinib in patients with metastatic phaeochromocytomas and paragangliomas. FIRSTMAPPP is a multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial done at 14 academic centres across four European countries. Eligible participants were adults (aged ≥18 years) with sporadic or inherited progressive metastatic phaeochromocytomas and paragangliomas. Patients were randomly assigned (1:1) to receive either oral sunitinib (37·5 mg per day) or placebo. Randomisation was stratified according to SDHB status (mutation present vs wild type) and number of previous systemic therapies (0 vs ≥1). Primary endpoint was the rate of progression-free survival at 12 months according to real-time central review (Response Evaluation Criteria in Solid Tumours version 1.1). On the basis of a two-step Simon model, we aimed for the accrual of 78 patients, assuming a 20% improvement of the 12-month progression-free survival rate from 20% to 40%, to conclude that sunitinib is effective. Crossover from the placebo group was allowed. This trial is registered with ClinicalTrials.gov, number NCT01371201, and is closed for enrolment. From Dec 1, 2011, to Jan 31, 2019, a total of 78 patients with progressive metastatic phaeochromocytomas and paragangliomas were enrolled (39 patients per group). 25 (32%) of 78 patients had germline SDHx variants and 54 (69%) had used previous therapies. The primary endpoint was met, with a 12-month progression-free survival in 14 of 39 patients (36% [90% CI 23-50]) in the sunitinib group. In the placebo group, the 12-month progression-free survival in seven of 39 patients was 19% (90% CI 11-31), validating the hypotheses of our study design. The most frequent grade 3 or 4 adverse events were asthenia (seven [18%] of 39 and one [3%] of 39), hypertension (five [13%] and four [10%]), and back or bone pain (one [3%] and three [8%]) in the sunitinib and placebo groups, respectively. Three deaths occurred in the sunitinib group: these deaths were due to respiratory insufficiency, amyotrophic lateral sclerosis, and rectal bleeding. Only the latter event was considered drug related. Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock. This first randomised trial supports the use of sunitinib as the medical option with the highest level of evidence for anti-tumour efficacy in progressive metastatic phaeochromocytomas and paragangliomas. French Ministry of Health, through the National Institute for Cancer, German Ministry of Education and Research, and the German Research Foundation within the CRC/Transregio 205/2, EU Seventh Framework Programme, and a private donator grant.

Online identity as a collective labeling process

Expressing identity socially involves a balance between conformity and innovation. One can adopt existing labels to express belonging to a certain community or introduce new labels to express an individual sense of identity. In such a process of co-creation, the existing identity labels of a community shape one’s sense of identity, while individual expression changes that of a community. Social media has introduced new opportunities to study the expression of collective identity. Here we study the group behavior of individuals defining their identities with hashtag self-labels in their Twitter profiles from mid-2017 through 2019. These timelines of personal self-labeling show behavior incorporating innovation, conservation, and social conformity when defining self. We show that the collective co-labeling of popular concepts in the context of identity, such as #resist and #maga, follow the dynamics of a modified Yule–Simon model balancing novelty and conformity. The dynamics of identity expression resemble the collective tagging processes of folksonomies, indicating a similarity between the collective tagging of external objects and the collective labeling of ourselves. Our work underpins a better understanding of how online environments mediate the evolution of collective identity which plays an increasingly important role in the establishment of community values and identity politics.

The uncertainty in mega-regional SEA and its coping methods in China's practice

Mega-regional strategic environmental assessment (RSEA) aims to provide decision-makers with scientific estimations and protective recommendations for regional development by taking inter-provincial space as work scopes, focalizing regional development as evaluation objects, and evaluating long-term ecological environmental impacts. Huge uncertainties inevitably exist in RSEA, affecting a reliable assessment. However, past literature offers limited guidance on how to systematically identify and address uncertainties in RSEAs. Thus, in light of uncertainty research in other environmental domains, an uncertainty typology of RSEA is constructed based on Simon's administrative model (1957) and Koernoev & Devuyst's decision situation (2016). Three uncertainty types including stochastic, epistemic, and technical uncertainties are developed to respectively interpret the variability-, knowledge-, and technic-related uncertainties. Various coping methods are identified, such as scenario analysis, modeling simulation, worst-case principles, adaptive management, etc. Then, practitioners' perception towards the uncertainty typology is investigated by a questionnaire survey, and the application of uncertainty coping approaches in RSEA practice is examined through case studies. Subsequently, the enlightenment of uncertainty handling in China's RSEA is proposed.

ANALISIS PROSES PENGAMBILAN KEPUTUSAN PEMBERIAN KREDIT PEMILIKAN RUMAH MENGGUNAKAN MODEL HERBERT A. SIMON DALAM MENERAPKAN METODE ANALYTICAL HIERARCHY PROCESS

House ownership credit is a government program provided by banks for the people. In the process, there are requirements that must be fulfilled by prospective clients before they get the loan. The requirements are used by the banks as the early assessment so that they can avoid non-performing loan. In making their decisions, whether to approve a loan or not, banks apply the Five Cs as the cautiousness principle in assessing their prospective clients. The objective of this research is to identify decision-making processes that is analyzed using he Herbert A. Simon model and Analytical Hierarchy Process. The Simon model consists of phases; they are intelligence, design, choice, and implementation. Meanwhile, the decision-making process applied by PT Bank Tabungan Negara branch of Madiun did not include the choice phase, which increase the probability of non-performing loan. The Analytical Hierarchy Process is applied to help in credit decision-making using the highest weight, and the applicable criteria is the Five Cs. This method provides assessment on paired comparisons with questionnaires given to the decision makers. This study finds that criterion with the highest weight is character (0.495739012), followed by capital (0.248389672), capacity (0.14426402), collateral (0.066977249), and condition (0.044630047). Therefore, the bank should consider character more in their decision.

Industry 4.0 Driven Result-oriented PSS: An Assessment in the Energy Management

Sustainability is a current challenge and all sectors, including the buildings one, are being called upon to provide a solution to mitigate climate change. The state of the art of energy management using ICT technology in building systems industry is characterized by a traditional monitoring approach which could assess the energy consumption of the building but that cannot manage and act the required action to improve the energy management according to a demand side approach. The aim of this paper is to overcome this traditional monitoring approach, presenting Simon, a new model proposed by Evogy, enabling a result-oriented Product Service System (PSS) for buildings through Cyber-Physical Systems, Artificial Intelligence, and Internet of Things adoption. The main findings highlight the benefits associated with the Simon model by virtue of digital-based predictive maintenance on the real system. In addition, its adoption allows the PSS provider to aggregate energy demand from the plethora of buildings and, according to digital technologies, not only monitor consumption but also implement equipment. Finally, the application case highlights the benefits are different and thus stands as a best practice for combining sustainability and digitization.

Gestión de riesgos del informe radiológico. Especial referencia al error diagnóstico

Of the four main categories of risk in the process of radiology, diagnostic errors account for 45% of the adverse effects. Based on Newell and Simon's model of cognitive processing, we propose a model of diagnostic error consisting of three subsystems: perceptive (reading the radiological image); cognoscitive (interpreting the image), and motor (documental management of the report) and three categories of errors (perceptive, cognoscitive, and motor). Using a dual methodological focus consisting of process management and risk management, we analyze common causes and specific causes, and we review the measures of control for these three categories: errors of perception (60%?70%); cognoscitive error (30%?40%), and motor error (documental management of the report). We map the risks of the diagnostic process in detail, pointing out the importance of systems to notify errors and incidents and of working continually to improve the entire process.

The role of grammar in transition-probabilities of subsequent words in English text.

Sentence formation is a highly structured, history-dependent, and sample-space reducing (SSR) process. While the first word in a sentence can be chosen from the entire vocabulary, typically, the freedom of choosing subsequent words gets more and more constrained by grammar and context, as the sentence progresses. This sample-space reducing property offers a natural explanation of Zipf's law in word frequencies, however, it fails to capture the structure of the word-to-word transition probability matrices of English text. Here we adopt the view that grammatical constraints (such as subject-predicate-object) locally re-order the word order in sentences that are sampled by the word generation process. We demonstrate that superimposing grammatical structure-as a local word re-ordering (permutation) process-on a sample-space reducing word generation process is sufficient to explain both, word frequencies and word-to-word transition probabilities. We compare the performance of the grammatically ordered SSR model in reproducing several test statistics of real texts with other text generation models, such as the Bernoulli model, the Simon model, and the random typewriting model.

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol

BackgroundCombination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients’ selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity.Methods/designCIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS, NRAS, BRAF wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+ 10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the possible mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with > 6 responses and the final sample is 34 patients with > 18 responses to draw positive conclusions. Secondary objectives include toxicity, responses’ duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients’ cetuximab-mediated ADCC and characterize the tumor microenvironment.DiscussionThe CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results’ interpretation as well as provide new insights in host-tumor interactions and cetuximab activity.Trial registrationThe CIFRA trial (version 0.0, June 21, 2018) has been registered into the NIH-US National Library of Medicine, ClinicalTrials.gov database with the identifier number (NCT03874062).

Proposing a Radial Basis Function and CSDM Indices to Predict the Traumatic Brain Injury Risk

BackgroundMany head injury indices and finite element (FE) head models have been proposed to predict traumatic brain injury (TBI). Although FE head models are suitable methods with high accuracy, they are computationally intensive. Head motion-based brain injury criteria are usually fast tools with lower accuracy. So, the objective of this study is to propose new criteria along with an artificial neural network model to predict TBI risks, which can be fast and accurate. MethodsFor this purpose, 250 FE head simulations have been carried out at 5 magnitudes and 50 rotational impact directions using the SIMon model. The effects of directions and magnitudes of rotational impacts were assessed for cumulative strain damage measure (CSDM) values. Next, statistical analysis and neural network were applied to predict CSDM values. ResultsThe results of the present research showed that the direction of rotation in the sagittal and frontal planes had a considerable effect on the CSDM values. Furthermore, new brain injury indices and a radial basis function neural network have been proposed to predict CSDM values which having high correlation coefficients with SIMon responses. ConclusionsThe results of this research demonstrated that rotational impact directions should be used to develop new head injury criteria being able to predict CSDM values. However, findings of present research proved that head motion-based brain injury criteria and RBF network can be used to predict FE head model responses with high speed and accuracy.

Long-Range Correlation Underlying Childhood Language and Generative Models.

Long-range correlation, a property of time series exhibiting relevant statistical dependence between two distant subsequences, is mainly studied in the statistical physics domain and has been reported to exist in natural language. By using a state-of-the-art method for such analysis, long-range correlation is first shown to occur in long CHILDES data sets. To understand why, generative stochastic models of language, originally proposed in the cognitive scientific domain, are investigated. Among representative models, the Simon model is found to exhibit surprisingly good long-range correlation, but not the Pitman-Yor model. Because the Simon model is known not to correctly reflect the vocabulary growth of natural languages, a simple new model is devised as a conjunct of the Simon and Pitman-Yor models, such that long-range correlation holds with a correct vocabulary growth rate. The investigation overall suggests that uniform sampling is one cause of long-range correlation and could thus have some relation with actual linguistic processes.

Application of shell jetting analysis to determine the location of the virtual origin in shaped charges

Shaped charges are designed to produce high-velocity jets for penetration. During jet formation, the liner collapses and converges at a point source, also known as the virtual origin (VO), along the distance–time plane. The location of the VO must be known to allow the development of penetration analytical models. Here we determined the location of the VO using the ANSYS® Autodyn 2D shaped charge jetting technique. Jetting analysis was conducted for two shaped charges of 18 and 32 mm diameter. The explosive and casing were represented by Eulerian two-dimensional finite difference grids, whereas the liner was modelled using a shell formulation. The summary/history of the jetting analysis was used to determine the VO position in the shaped charges. Interpolating the point of intersection on the liner between the jet velocity (U-Jet) and the cumulative jet mass revealed the location of the VO at a distance equivalent to approximately two-thirds of the inner cone diameter of the shaped charges, in agreement with earlier studies based on different methods. Validation of this technique using the DiPersio, Simon and Merendino (DSM) model based on the Allison-Vitalli equation also showed good agreement with the numerical results.

Continuum rich-get-richer processes: Mean field analysis with an application to firm size.

Classical rich-get-richer models have found much success in being able to broadly reproduce the statistics and dynamics of diverse real complex systems. These rich-get-richer models are based on classical urn models and unfold step by step in discrete time. Here, we consider a natural variation acting on a temporal continuum in the form of a partial differential equation (PDE). We first show that the continuum version of Simon's canonical preferential attachment model exhibits an identical size distribution. In relaxing Simon's assumption of a linear growth mechanism, we consider the case of an arbitrary growth kernel and find the general solution to the resultant PDE. We then extend the PDE to multiple spatial dimensions, again determining the general solution. We then relax the zero-diffusion assumption and find an envelope of solutions to the general model in the presence of small fluctuations. Finally, we apply the model to size and wealth distributions of firms. We obtain power-law scaling for both to be concordant with simulations as well as observational data, providing a parsimonious theoretical explanation for these phenomena.

A multicenter phase II study of the efficacy and safety of quisinostat (an HDAC inhibitor) in combination with paclitaxel and carboplatin chemotherapy (CT) in patients (pts) with recurrent platinum resistant high grade serous epithelial ovarian, primarily peritoneal or fallopian tube carcinoma cancer (OC).

5541 Background: Quisinostat is an orally bioavailable potent pan-histone deacetylase inhibitor. Combinations of HDAC inhibitors with paclitaxel or cisplatin demonstrate promising results in preclinical models with cisplatin and paclitaxel resistant OC. In phase Ib study the dosage of Quisinostat in combination of paclitaxel and carboplatin recommended for the phase II study was 12 mg. We report results of the phase II study of Quisinostat in combination with paclitaxel and carboplatin in pts with recurrent platinum resistantOC. Methods: the main inclusion criteria was tumor progression observed not less than 1 month and no more than 6 months after completion of the planned number of cycles of 1st line platinum/paclitaxel based CT. Quisinostat was administered at dose 12 mg p.o. each 3 week cycle on Days 1, 3, 5, 7, 9, 11 with of paclitaxel (175 mg/m2) and carboplatin (AUC5) on Day 7 of each cycle, for 2ndline. Pts received up to 6 cycles. The primary efficacy endpoint is the objective response rate (ORR) verified by the ICR. The secondary endpoints include safety, progression free survival (PFS) and overall survival. The study design implies the use of the two-stage Simon model: 29 patients who underwent treatment would provide 80% power for hypothesis testing in order to frequency of the ORR 30% (α = 0.05). Results: 31 pts were enrolled (30 pts evaluated). Median age was 57 years. Twenty one pts (67.7%) received all 6 cycles of therapy. ORR was 50.0% (15 pts). Median duration of response was 5 months (4.2-5.7). Median PFS - 6 months (95%CI 4.4-7.6). Any SAE were seen in 16.1% pts, AE of grade 3 and 4 – in 71% and 48.4% pts temporarily discontinued therapy due to AE. Dose reduction of CT due to AE was performed in 22.6% pts. The most common adverse events were neutropenia – 67,7%, nausea – 61.3%, weakness – 29%, thrombocytopenia – 22.6%, neuropathy – 19.4%, vomiting – 19.4%. Conclusions: Quisinostat in combination with paclitaxel and carboplatin in pts with recurrent platinum resistant ovarian cancer showed high efficacy and good tolerability Clinical trial information: NCT02948075.

Simon's fundamental rich-get-richer model entails a dominant first-mover advantage.

Herbert Simon's classic rich-get-richer model is one of the simplest empirically supported mechanisms capable of generating heavy-tail size distributions for complex systems. Simon argued analytically that a population of flavored elements growing by either adding a novel element or randomly replicating an existing one would afford a distribution of group sizes with a power-law tail. Here, we show that, in fact, Simon's model does not produce a simple power-law size distribution as the initial element has a dominant first-mover advantage, and will be overrepresented by a factor proportional to the inverse of the innovation probability. The first group's size discrepancy cannot be explained away as a transient of the model, and may therefore be many orders of magnitude greater than expected. We demonstrate how Simon's analysis was correct but incomplete, and expand our alternate analysis to quantify the variability of long term rankings for all groups. We find that the expected time for a first replication is infinite, and show how an incipient group must break the mechanism to improve their odds of success. We present an example of citation counts for a specific field that demonstrates a first-mover advantage consistent with our revised view of the rich-get-richer mechanism. Our findings call for a reexamination of preceding work invoking Simon's model and provide an expanded understanding going forward.

Externalities in economies with endogenous sharing rules

Endogenous sharing rules were introduced by Simon and Zame [16] to model payoff indeterminacy in discontinuous games. They prove the existence in every compact strategic game of a mixed Nash equilibrium and an associated sharing rule. We extend their result to economies with externalities [1] where, by definition, players are restricted to pure strategies. We also provide a new interpretation of payoff indeterminacy in Simon and Zame's model in terms of preference incompleteness.

Herdan-Heaps Law Corresponds to Lotka’s Law: A Dynamic Perspective from Simon’s Model

Herdan-Heaps law and Lotka’s law are two important laws in linguistics and many other fields, which are often found to coexist in many languages. Herdan-Heaps law describes the type-token relation between number of distinct words and text length. Lotka’s law concerns the fraction of words with a given number of word occurrences. Utilising a variant of the Simon model, this work demonstrates that if the growth rate of different words follow Herdan-Heaps law, with an exponent in the interval (0,1), then the exponents of Lotka’s law and Herdan-Heaps law are identical. A biparameter power law distribution, i.e. the Waring distribution, is derived within the framework of Simon’s model. Estimators of the Waring distribution parameters are determined and numerical illustrations are provided.

Random Graphs Associated to Some Discrete and Continuous Time Preferential Attachment Models

We give a common description of Simon, Barab\'asi--Albert, II-PA and Price growth models, by introducing suitable random graph processes with preferential attachment mechanisms. Through the II-PA model, we prove the conditions for which the asymptotic degree distribution of the Barab\'asi--Albert model coincides with the asymptotic in-degree distribution of the Simon model. Furthermore, we show that when the number of vertices in the Simon model (with parameter $\alpha$) goes to infinity, a portion of them behave as a Yule model with parameters $(\lambda,\beta) = (1-\alpha,1)$, and through this relation we explain why asymptotic properties of a random vertex in Simon model, coincide with the asymptotic properties of a random genus in Yule model. As a by-product of our analysis, we prove the explicit expression of the in-degree distribution for the II-PA model, given without proof in \cite{Newman2005}. References to traditional and recent applications of the these models are also discussed.

Guarana (Paullinia cupana) Improves Anorexia in Patients with Advanced Cancer

ABSTRACTPurpose: Anorexia is prevalent in cancer patients with advanced disease. In this pilot phase II, open label, nonrandomized trial, we evaluated the efficacy and safety of guarana (Paullinia cupana) in patients with cancer and weight loss. Methods: We included advanced cancer patients with decreased appetite and weight loss of more than 5% from their baseline. All of the patients received 50 mg of the crude dry extract of guarana twice a day for 4 weeks. The trial was designed in two phases (Simon model). We considered a positive response in the first phase to be at least 5% weight gain or a three-point improvement in the appetite scale in at least three of the first 18 evaluable patients. Results: Of the 34 eligible patients, 30 were included and 18 completed the protocol. Only one patient abandoned the protocol due to toxicity (grade II arthralgia). No grade 3 or 4 toxicities and no significant differences in nausea, weight loss, or quality of life (FACT-G) occurred. Only two of the 18 patients who completed the study had weight gain above 5% from their baseline, whereas six patients had at least a 3-point improvement in the visual appetite scale. The M.D. Anderson Symptom Inventory (MDASI) was used to evaluate several symptoms, and we observed a significant decrease in the lack of appetite (p = 0.02) and in somnolence (p = 0.0142). Conclusion: We concluded that the weight stabilization and increased appetite that we observed in this study justify further studies of guarana in this patient population.

Relationship of guarana (Paullinia cupana) on anorexia in patients with advanced cancer.

e20532 Background: Anorexia is prevalent in cancer patients with advanced disease. There are currently some treatments for cancer anorexia-cachexia syndrome (CACS), including corticosteroids, progestogens, cannabinoids and anabolic steroids. However, none of these treatments alone increases appetite and weight with few side effects. In this pilot phase II, open label, non-randomized trial, we evaluated the efficacy and safety of guarana (Paullinia cupana) in patients with cancer and weight loss. Methods: We included advanced cancer patients with decreased appetite and weight loss of more than 5% from their baseline in the past 6 months. All of the patients received 50 mg of the crude dry extract of guarana twice a day for 4 weeks. The trial was designed in 2 phases (Simon model). We considered a positive response in the first phase to be at least 5% weight gain or a 3-point improvement in the appetite scale in at least 3 of the first 18 evaluable patients. Results: Of the 34 eligible patients, 30 were included and 18 completed the protocol. Only 1 patient abandoned the protocol due to toxicity (grade II arthralgia). There were no grade 3 or 4 toxicities. There were no significant differences in nausea, weight loss and quality of life (FACT-G). Only 2 of the 18 patients who completed the study had weight gain above 5% from their baseline, whereas 6 patients had at least a 3-point improvement in the visual appetite scale. The M.D. Anderson Symptom Inventory (MDASI) was used to evaluate several symptoms, and we observed a significant decrease in lack of appetite (p=0.02) and in somnolence (p=0.0142). Conclusions: We concluded that the weight stabilization and increased appetite we observed in this study justify further studies of guarana in this patient population. Clinical trial information: NCT01540019.

Scale-free phenomenon in industries in China

In this paper, we investigate the data of industries in China and find that the frequency distributions of fixed assets and fixed-assets’ investment of industries obey power laws. We show that these power-law modes can be explained by the rules of the Simon Model, rather than the existing investment theories such as the classical investment theory or acceleration principle. Moreover, the mechanism of the investment distribution may be similar to the forest-fire model of self-organizing criticality. By introducing the complex system methods, this research changes the traditional opinion of the investment and gains some meaningful understanding in the dynamics of industries and the economic cycle.