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1

McCausland, Beth, Nicola Minicozzi, Siobhan O'Halloran, Avril Ward e Kerry Elliott. "Increasing staff confidence about domestic abuse identification, disclosure and safeguarding in a community mental health team". BJPsych Open 7, S1 (giugno 2021): S146—S147. http://dx.doi.org/10.1192/bjo.2021.413.

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AimsTo increase staff confidence about identifying Domestic Abuse (DA), particularly regarding ‘how to ask’ to encourage disclosure and the pathways available for appropriately safeguarding survivors; in a Community Mental Health Team (CMHT) setting.BackgroundDA is bi-directionally associated with mental health (MH) disorders; 1:4 women in contact with MH services are currently experiencing DA. MH professionals (MHPs) are in a privileged position to identify DA and support survivors. However, this is dependent on MHPs receiving adequate training about DA. For this, we collaborated with Pathfinder, a national pilot project run by a consortium of five expert partners that aims to establish comprehensive health practice in relation to DA and Violence Against Women & Girls in Acute Hospital Trusts, MH Trusts and Primary Care. In Southampton, Pathfinder has funded two domestic and sexual abuse (DSA) advocates to both train MH staff and take a small caseload of MH service users who are experiencing abuse.MethodWe conducted a baseline survey of staff confidence across the following domains:Knowing the legal definition of DA,The process used to escalate a DA concern,How to make a referral,How to complete DASH forms,How and when to refer to Pathfinder,What the following acronyms mean: PIPPA, MAPPA, MARAC, IDVA, DASH,What HRDA and MASH mean,How to ask about DA,Who to signpost service users to if they make a disclosure, and when to involve the police.We presented the survey results at the regional Pathfinder strategic group, with Trust management representatives present. This project fits within the strategic group's sustainability aims to increase DA awareness and safeguarding processes across the Trust.The Pathfinder funded DSA Advisors delivered a four-hour training package targeting the surveyed questions and wider information on DA. We then re-surveyed to see if staff confidence had increased. We are currently analyzing the number of referrals to the Pathfinder service pre- and post-training.ResultStaff confidence increased across all domains following the training (% mean increase): Qs1 (35%), Qs2 (9%), Qs3 (45%), Qs4 (81%), Qs5 (25%), Qs6 (49%), Qs7 (89%), Qs8 (62%) and Qs9 (48%).We have now arranged a bi-monthly drop-in at the CMHT by the DSA advisor who provided the training, to embed the link between the services and maintain staff confidence. We will circulate these results to advocate that this training is provided across the Trust.
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Song, Yong-jia, Jia-min Bao, Long-yun Zhou, Gan Li, Kim Sia Sng, Yong-jun Wang, Qi Shi e Xue-jun Cui. "An Analysis of the Anti-Neuropathic Effects of Qi She Pill Based on Network Pharmacology". Evidence-Based Complementary and Alternative Medicine 2020 (5 maggio 2020): 1–15. http://dx.doi.org/10.1155/2020/7193832.

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Background. Qi She Pill (QSP) is a traditional prescription for the treatment of neuropathic pain (NP) that is widely used in China. However, no network pharmacology studies of QSP in the treatment of NP have been conducted to date. Objective. To verify the potential pharmacological effects of QSP on NP, its components were analyzed via target docking and network analysis, and network pharmacology methods were used to study the interactions of its components. Materials and Methods. Information on pharmaceutically active compounds in QSP and gene information related to NP were obtained from public databases, and a compound-target network and protein-protein interaction network were constructed to study the mechanism of action of QSP in the treatment of NP. The mechanism of action of QSP in the treatment of NP was analyzed via Gene Ontology (GO) biological process annotation and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway enrichment, and the drug-like component-target-pathway network was constructed. Results. The compound-target network contained 60 compounds and 444 corresponding targets. The key active compounds included quercetin and beta-sitosterol. Key targets included PTGS2 and PTGS1. The protein-protein interaction network of the active ingredients of QSP in the treatment of NP featured 48 proteins, including DRD2, CHRM, β2-adrenergic receptor, HTR2A, and calcitonin gene-related peptide. In total, 53 GO entries, including 35 biological process items, 7 molecular function items, and 11 cell related items, were identified. In addition, eight relevant (KEGG) pathways were identified, including calcium, neuroactive ligand-receptor interaction, and cAMP signaling pathways. Conclusion. Network pharmacology can help clarify the role and mechanism of QSP in the treatment of NP and provide a foundation for further research.
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Kling, Gerhard, Charles Harvey e Mairi Maclean. "Establishing Causal Order in Longitudinal Studies Combining Binary and Continuous Dependent Variables". Organizational Research Methods 20, n. 4 (30 novembre 2015): 770–99. http://dx.doi.org/10.1177/1094428115618760.

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Longitudinal studies with a mix of binary outcomes and continuous variables are common in organizational research. Selecting the dependent variable is often difficult due to conflicting theories and contradictory empirical studies. In addition, organizational researchers are confronted with methodological challenges posed by latent variables relating to observed binary outcomes and within-subject correlation. We draw on Dueker’s qualitative vector autoregression (QVAR) and Lunn, Osorio, and Whittaker’s multivariate probit model to develop a solution to these problems in the form of a qualitative short panel vector autoregression (QSP-VAR). The QSP-VAR combines binary and continuous variables into a single vector of dependent variables, making every variable endogenous a priori. The QSP-VAR identifies causal order, reveals within-subject correlation, and accounts for latent variables. Using a Bayesian approach, the QSP-VAR provides reliable inference for short time dimension longitudinal research. This is demonstrated through analysis of the durability of elite corporate agents, social networks, and firm performance in France. We provide our OpenBUGS code to enable implementation of the QSP-VAR by other researchers.
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van der Graaf, Piet. "SC3.1 - Introduction to QSP". Drug Metabolism and Pharmacokinetics 35, n. 1 (2020): S3. http://dx.doi.org/10.1016/j.dmpk.2020.04.277.

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Matteelli, Alberto, Nuccia Saleri, Zeno Bisoffi, Giampietro Gregis, Giovanni Gaiera, Raffaella Visonà, Simona Tedoldi, Carla Scolari, Stefania Marocco e Maurizio Gulletta. "Mefloquine versus Quinine plus Sulphalene-Pyrimethamine (Metakelfin) for Treatment of Uncomplicated Imported Falciparum Malaria Acquired in Africa". Antimicrobial Agents and Chemotherapy 49, n. 2 (febbraio 2005): 663–67. http://dx.doi.org/10.1128/aac.49.2.663-667.2005.

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ABSTRACT We conducted a multicenter, randomized, open-label trial to compare mefloquine with a 3-day quinine plus sulphalene-pyrimethamine (SP) regimen for the treatment of imported uncomplicated malaria acquired in Africa. The end points of the study were efficacy, tolerability, and length of hospital stay. From July 1999 to February 2003, 187 patients were enrolled in five centers in Italy, of whom 93 were randomized to receive mefloquine (the M group) and 94 were randomized to receive quinine plus SP (the QSP group). Immigrants and visiting relatives and friends represented 90% of the cases and were mainly from western African countries. A slightly increased proportion of cases in the QSP group had abnormal alanine aminotransferase levels at the baseline. The early cure rate was similar in the two groups: 98.9% (confidence interval [CI] = 97 to 100%) in the M group and 96.8% (CI = 93 to 100%) in the QSP group. The extended follow-up was completed by 135 subjects (72.2%), and no case of recrudescence was detected. There were no differences in the parasite clearance time, but patients in the M group had shorter mean fever clearance time (35.9 h versus 44.4 h for the QSP group; P = 0.05) and a shorter mean hospital stay (3.9 days versus 4.6 days for the QSP group; P = 0.007). The overall proportions of reported side effects were similar in the two groups, but patients in the M group had a significantly higher rate of central nervous system disturbances (29.0% versus 9.6% for the QSP group; P < 0.001).
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Meng, Fuxue, e Xiaomai Tao. "Application value of quantitative system pharmacology in drug discovery for traditional Chinese medicine". Journal of Medical Care Research and Review 3, n. 9 (1 settembre 2020): 425–36. http://dx.doi.org/10.15520/mcrr.v3i9.113.

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Quantitative system pharmacology (QSP) is a discipline that combines computational models of systems biology and systems pharmacology. With the development of high-throughput genomics techniques (genomics, transcriptomics, proteomics, and metabolomics) as well as computer and bioinformatics methods, systems biology and systems pharmacology modeling are widely used to comprehend human biology and disease progression, predict the effectiveness and safety of drug candidates. Due to the advancement of big data and high-quality database, the application of QSP, especially the pre-clinical stage that guides early drug discovery, is increasingly widespread. The traditional drug discovery process takes a long time yet has a low success rate. The early intervention and full participation of QSP in the development of new drugs discovery can form a model-led drug development model to improve the efficiency of drug discovery and scientific appraise, reduce the cost of research and development, and shorten the time to market for new drugs. This article reviews the differences between QSP and other quantitative pharmacology, the problems faced by traditional Chinese medicine research, and the value of QSP in traditional Chinese medicine research, with a view to providing reference and support for the research and development of new traditional Chinese medicine.
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Katritzky, Alan R., Svetoslav Slavov, Maksim Radzvilovits, Iva Stoyanova-Slavova e Mati Karelson. "Computational Chemistry Approaches for Understanding how Structure Determines Properties". Zeitschrift für Naturforschung B 64, n. 6 (1 giugno 2009): 773–77. http://dx.doi.org/10.1515/znb-2009-0625.

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The establishment of quantitative relationships between numerous molecular properties and chemical structures is now of great importance to society in understanding and improving environmental, medicinal and technological aspects of life. Quantitative structure-activity (property) relationships (QSA(P)R) relate physical, chemical, physico-chemical, technological and biological properties of compounds to their structure. A major factor driving the widespread use of QSP(A)R models is the rational estimation of properties of new compounds, without first synthesizing and testing them. Some of our recent findings in the field are briefly discussed below.
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Stern, Andrew M., Mark E. Schurdak, Ivet Bahar, Jeremy M. Berg e D. Lansing Taylor. "A Perspective on Implementing a Quantitative Systems Pharmacology Platform for Drug Discovery and the Advancement of Personalized Medicine". Journal of Biomolecular Screening 21, n. 6 (8 marzo 2016): 521–34. http://dx.doi.org/10.1177/1087057116635818.

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Drug candidates exhibiting well-defined pharmacokinetic and pharmacodynamic profiles that are otherwise safe often fail to demonstrate proof-of-concept in phase II and III trials. Innovation in drug discovery and development has been identified as a critical need for improving the efficiency of drug discovery, especially through collaborations between academia, government agencies, and industry. To address the innovation challenge, we describe a comprehensive, unbiased, integrated, and iterative quantitative systems pharmacology (QSP)–driven drug discovery and development strategy and platform that we have implemented at the University of Pittsburgh Drug Discovery Institute. Intrinsic to QSP is its integrated use of multiscale experimental and computational methods to identify mechanisms of disease progression and to test predicted therapeutic strategies likely to achieve clinical validation for appropriate subpopulations of patients. The QSP platform can address biological heterogeneity and anticipate the evolution of resistance mechanisms, which are major challenges for drug development. The implementation of this platform is dedicated to gaining an understanding of mechanism(s) of disease progression to enable the identification of novel therapeutic strategies as well as repurposing drugs. The QSP platform will help promote the paradigm shift from reactive population-based medicine to proactive personalized medicine by focusing on the patient as the starting and the end point.
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Gong, Chang, Alvaro Ruiz-Martinez, Holly Kimko e Aleksander S. Popel. "A Spatial Quantitative Systems Pharmacology Platform spQSP-IO for Simulations of Tumor–Immune Interactions and Effects of Checkpoint Inhibitor Immunotherapy". Cancers 13, n. 15 (26 luglio 2021): 3751. http://dx.doi.org/10.3390/cancers13153751.

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Quantitative systems pharmacology (QSP) models have become increasingly common in fundamental mechanistic studies and drug discovery in both academic and industrial environments. With imaging techniques widely adopted and other spatial quantification of tumor such as spatial transcriptomics gaining traction, it is crucial that these data reflecting tumor spatial heterogeneity be utilized to inform the QSP models to enhance their predictive power. We developed a hybrid computational model platform, spQSP-IO, to extend QSP models of immuno-oncology with spatially resolved agent-based models (ABM), combining their powers to track whole patient-scale dynamics and recapitulate the emergent spatial heterogeneity in the tumor. Using a model of non-small-cell lung cancer developed based on this platform, we studied the role of the tumor microenvironment and cancer–immune cell interactions in tumor development and applied anti-PD-1 treatment to virtual patients and studied how the spatial distribution of cells changes during tumor growth in response to the immune checkpoint inhibition treatment. Using parameter sensitivity analysis and biomarker analysis, we are able to identify mechanisms and pretreatment measurements correlated with treatment efficacy. By incorporating spatial data that highlight both heterogeneity in tumors and variability among individual patients, spQSP-IO models can extend the QSP framework and further advance virtual clinical trials.
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Sobha, Varsha V., NK Sapna Varma e VV Ajith. "Comparative Evaluation of Laser Etching and Acid Etching: An in vitro Study". International Journal of Laser Dentistry 6, n. 1 (2016): 6–11. http://dx.doi.org/10.5005/jp-journals-10022-1079.

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ABSTRACT Introduction Recent innovations in bonding propose laser ablation as an alternative method to acid etching. Objectives The objective of this study is to compare the effect of laser irradiation at medium-short pulse (MSP) mode, quantum-square pulse (QSP) mode, and acid etching on the shear bond strength (SBS) of orthodontic brackets to enamel. Materials and methods Forty-two premolars were allocated to three groups (14 each): (1) 37% phosphoric acid etching; (2) erbium-doped yttrium aluminum garnet (Er:YAG) laser etching with MSP mode; (3) Er:YAG laser etching with quantum-square pulse mode. Metallic brackets were bonded with Transbond XT. After photo polymerization, the SBS values were recorded with universal testing machine. Surface morphology was evaluated with scanning electron microscopy (SEM). The remaining adhesive was assessed using adhesive remnant index (ARI). Results Nonparametric test was used to analyze the statistical significance. A mean rank of 18.29 and 10.71 was obtained for QSP mode and acid etching with p = 0.015, 18.14; and 10.86 for MSP mode and acid etching with p = 0.019; and 14 and 15 for QSP mode and MSP mode with p = 0.748. Statistically significant difference was found between laser and acid-etched group. The SEM scan showed MSP mode with regular and uniform surface, like acid-etched sample, whereas QSP samples had irregular and severely rough surface. The ARI indicates that failure sites are mainly at the enamel/adhesive interface in the acid-etched and MSP mode group and at the bracket base/adhesive interface in QSP mode group. Conclusion Laser etching in MSP mode is a successful alternative to acid etching, and provides a safer debonding of the brackets from the enamel surface without causing fractures. How to cite this article Sobha VV, Varma NKS, Ajith VV. Comparative Evaluation of Laser Etching and Acid Etching: An in vitro Study. Int J Laser Dent 2016;6(1):6-11.
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Anwar, Bilal, Muhammad Imran Ashraf e Aftab Alam. "OPPORTUNITIES AND RISK FACTORS IN PUBLIC-PRIVATE PARTNERSHIP ON ENERGY: A CRITICAL ANALYSIS OF SOLAR PHOTOVOLTAIC PLANT AT BAHAWALPUR". Global Political Review 3, n. 2 (30 dicembre 2018): 61–74. http://dx.doi.org/10.31703/gpr.2018(iii-ii).07.

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This study delineates a 1000 Megawatt (MW) very large scale Photovoltaic (PV) system designed in three phases, from which 100 MW has functional and the remaining two phases of 300MW, 600 MW has yet to be functional at Quaid-eAzam solar park (QSP) in Cholistan desert near Bahawalpur City of Pakistan. This study describes the opportunities and risks in the construction of solar PV plant (QSP), which is constructed through public-private partnership (3P).This study uses the case study as a part of research methodology. Firstly it explains about 3Ps, their various types and necessity. Secondly, explores the critical factors in the construction of QSP PV Plant through PESTLE (political, economic, social, technological, legal, environmental) analysis. Thirdly outlines the effect of RE projects on the socioeconomic status of the periphery which is ignored in previous studies. The recommendations will guide the policymakers how they can embed social acceptance in RE projects.
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Shi, Shuangning, Yong Shang, Qinglin Liang e Bin Liang. "Analysis and simulation of QSP beamformer". Journal of Electronics (China) 24, n. 6 (novembre 2007): 812–14. http://dx.doi.org/10.1007/s11767-006-0266-3.

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Nathorst-Boos, J. "An evaluation of the QSP and the QPP: two methods for measuring patient satisfaction". International Journal for Quality in Health Care 13, n. 3 (1 giugno 2001): 257–64. http://dx.doi.org/10.1093/intqhc/13.3.257.

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Sağır, Serkan, Aslıhan Usumez, Ebru Ademci e Serdar Usumez. "Effect of enamel laser irradiation at different pulse settings on shear bond strength of orthodontic brackets". Angle Orthodontist 83, n. 6 (13 giugno 2013): 973–80. http://dx.doi.org/10.2319/111412-872.1.

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ABSTRACT Objective: To compare the effect of laser irradiation at two different pulse settings and acid etching on the shear bond strength (SBS) of orthodontic brackets to enamel. Materials and Methods: Thirty-six premolars were allocated to three groups (n = 12): (1) 37% phosphoric acid etching, (2) erbium-doped yttrium aluminum garnet (Er:YAG) laser etching with medium-short pulse mode (MSP; 100 µs, 120 mj, 10 Hz, 1.2 W), and (3) Er:YAG laser etching with quantum-square pulse mode (QSP; 120 mj, 10 Hz, 1.2 W). Metallic brackets were bonded with Transbond XT. After photopolymerization, the samples were subjected to 5000 thermal cycles and debonded with a universal testing machine, and the SBS values were recorded. Surface morphology was evaluated with profilometric examination, scanning electron microscopy, and atomic force microscopy. The adhesive remnant index (ARI) was evaluated to assess the remaining adhesive. Results: The results of SBS testing were analyzed by one-way analysis of variance and Tukey honestly significant diffference tests. The mean SBS values of QSP and MSP laser groups were 11.80 ± 2.7 MPa and 10.10 ± 4.5 MPa, respectively, and the QSP group demonstrated significantly higher SBS (P &lt; .01) than that of the acid-etched group (6.6 ± 2.4 MPa). No significant difference was observed between the SBS values of the two laser groups (P &lt; .05). The difference between the ARI scores of the laser groups and the acid-etched group was statistically significant (P &lt; .05). Conclusion: Laser etching at MSP and QSP modes present successful alternatives to acid etching; however, long-term clinical studies are required to verify clinical success.
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Zhang, Xiaocun, Yanwu Fu, Yiru Xu, Ying Guo e Huinan Wang. "QTL mapping for the textural property traits of northern-style Chinese steamed bread by using recombinant inbred lines of wheat". Crop and Pasture Science 70, n. 6 (2019): 509. http://dx.doi.org/10.1071/cp18593.

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Textural property is one of the most important factors influencing the quality of northern-style Chinese steamed bread (CSB). We detected quantitative trait loci (QTLs) for the textural properties of CSB by using 184 recombinant inbred lines derived from a cross between two Chinese winter wheat (Triticum aestivum L.) varieties, Linmai6 and Tainong18. Eighteen putative QTLs were detected on 14 chromosomes: 1B, 1D, 2A, 2B, 2D, 3A, 3B, 4A, 4B, 5B, 6A, 6B, 7B, and 7D. Six textural quality traits, one QTL for hardness (QHa-4A), three QTLs for springiness (QSp-3B, QSp-4B, and QSp-5B), seven QTLs for cohesiveness (QCo-6A, QCo-7B.1, QCo-7B.2, QCo-3A, QCo-1D, QCo-2B.1, and QCo-2B.2), four QTLs for resilience (QRe-2D, QRe-2A, QRe-7D, and QRe-1B), two QTLs for gumminess (QGu-6B, and QGu-3B), and one QTL for chewiness (QCh-7D) were detected. The contributions of the QTLs ranged from 6.19% to 15.74%. The present study enhances understanding of the genetic basis for the textural properties of northern-style CSB and provides the basis for gene mapping of these traits.
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Sayama, Hiroyuki, Yasuhisa Nagasaka e Kenji Tabata. "An introduction to QSP modeling for pharmacologists". Folia Pharmacologica Japonica 154, n. 3 (2019): 143–50. http://dx.doi.org/10.1254/fpj.154.143.

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Kirouac, Daniel C. "How Do We “Validate” a QSP Model?" CPT: Pharmacometrics & Systems Pharmacology 7, n. 9 (22 agosto 2018): 547–48. http://dx.doi.org/10.1002/psp4.12310.

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Thompson, R. Adam. "SC3.2 - Application of QSP in drug discovery". Drug Metabolism and Pharmacokinetics 35, n. 1 (2020): S3. http://dx.doi.org/10.1016/j.dmpk.2020.04.278.

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Wang, Hanwen, Huilin Ma, Richard J. Sové, Leisha A. Emens e Aleksander S. Popel. "Quantitative systems pharmacology model predictions for efficacy of atezolizumab and nab-paclitaxel in triple-negative breast cancer". Journal for ImmunoTherapy of Cancer 9, n. 2 (febbraio 2021): e002100. http://dx.doi.org/10.1136/jitc-2020-002100.

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BackgroundImmune checkpoint blockade therapy has clearly shown clinical activity in patients with triple-negative breast cancer, but less than half of the patients benefit from the treatments. While a number of ongoing clinical trials are investigating different combinations of checkpoint inhibitors and chemotherapeutic agents, predictive biomarkers that identify patients most likely to benefit remains one of the major challenges. Here we present a modular quantitative systems pharmacology (QSP) platform for immuno-oncology that incorporates detailed mechanisms of immune–cancer cell interactions to make efficacy predictions and identify predictive biomarkers for treatments using atezolizumab and nab-paclitaxel.MethodsA QSP model was developed based on published data of triple-negative breast cancer. With the model, we generated a virtual patient cohort to conduct in silico virtual clinical trials and make retrospective analyses of the pivotal IMpassion130 trial that led to the accelerated approval of atezolizumab and nab-paclitaxel for patients with programmed death-ligand 1 (PD-L1) positive triple-negative breast cancer. Available data from clinical trials were used for model calibration and validation.ResultsWith the calibrated virtual patient cohort based on clinical data from the placebo comparator arm of the IMpassion130 trial, we made efficacy predictions and identified potential predictive biomarkers for the experimental arm of the trial using the proposed QSP model. The model predictions are consistent with clinically reported efficacy endpoints and correlated immune biomarkers. We further performed a series of virtual clinical trials to compare different doses and schedules of the two drugs for simulated therapeutic optimization.ConclusionsThis study provides a QSP platform, which can be used to generate virtual patient cohorts and conduct virtual clinical trials. Our findings demonstrate its potential for making efficacy predictions for immunotherapies and chemotherapies, identifying predictive biomarkers, and guiding future clinical trial designs.
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Kallis, Antonis, Kosmas Tolidis, Paris Gerasimou, Nor Gutknecht e Eugenia Koliniotou-Koumpia. "Comparative Study of the Restoration Quality in Cavities prepared with Er:YAG Laser in Quantum Square Pulse Mode and Conventional Method". International Journal of Laser Dentistry 6, n. 1 (2016): 31–37. http://dx.doi.org/10.5005/jp-journals-10022-1083.

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ABSTRACT Nowadays, dental treatment has been enriched by the use of lasers. The introduction of the novel treatment parameter of quantum square pulse (QSP) constitutes an additional challenge to older techniques, promising minimally invasive treatments. The aim of this study is to comparatively investigate the quality of cavity preparations using erbium-doped yttrium-aluminum-garnet (Er:YAG) laser with QSP technology as opposed to the conventional bur. The Er:YAG laser (2940 nm) has been used at 120 mJ energy level in QSP and medium short pulse (125 μs) modes. Subsequently, the dentin and enamel surfaces were examined using scanning electron microscopy techniques and compared with cuttings prepared with conventional bur. The laser-treated dentin samples exhibited relatively homogenous surfaces without smear layer and with open dentinal tubules. Laser-treated enamel showed scaly surfaces but again free of smear layer. In contrast, both dentin and enamel samples treated with the conventional bur showed abundance of smear layer, groove marks, small-scale cracks, and closed dentinal tubules. How to cite this article Kallis A, Tolidis K, Gerasimou P, Gutknecht N, Koliniotou-Koumpia E. Comparative Study of the Restoration Quality in Cavities prepared with Er:YAG Laser in Quantum Square Pulse Mode and Conventional Method. Int J Laser Dent 2016;6(1):31-37.
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Charoenkwan, Phasit, Nalini Schaduangrat, Chanin Nantasenamat, Theeraphon Piacham e Watshara Shoombuatong. "iQSP: A Sequence-Based Tool for the Prediction and Analysis of Quorum Sensing Peptides Using Informative Physicochemical Properties". International Journal of Molecular Sciences 21, n. 1 (20 dicembre 2019): 75. http://dx.doi.org/10.3390/ijms21010075.

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Understanding of quorum-sensing peptides (QSPs) in their functional mechanism plays an essential role in finding new opportunities to combat bacterial infections by designing drugs. With the avalanche of the newly available peptide sequences in the post-genomic age, it is highly desirable to develop a computational model for efficient, rapid and high-throughput QSP identification purely based on the peptide sequence information alone. Although, few methods have been developed for predicting QSPs, their prediction accuracy and interpretability still requires further improvements. Thus, in this work, we proposed an accurate sequence-based predictor (called iQSP) and a set of interpretable rules (called IR-QSP) for predicting and analyzing QSPs. In iQSP, we utilized a powerful support vector machine (SVM) cooperating with 18 informative features from physicochemical properties (PCPs). Rigorous independent validation test showed that iQSP achieved maximum accuracy and MCC of 93.00% and 0.86, respectively. Furthermore, a set of interpretable rules IR-QSP was extracted by using random forest model and the 18 informative PCPs. Finally, for the convenience of experimental scientists, the iQSP web server was established and made freely available online. It is anticipated that iQSP will become a useful tool or at least as a complementary existing method for predicting and analyzing QSPs.
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Larner, Andrew J. "Applying Kraemer’s Q (Positive Sign Rate): Some Implications for Diagnostic Test Accuracy Study Results". Dementia and Geriatric Cognitive Disorders Extra 9, n. 3 (20 dicembre 2019): 389–96. http://dx.doi.org/10.1159/000503026.

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Background/Aims: Sensitivity and specificity (Sens, Spec) are not invariant properties of diagnostic and screening tests, but vary in different patient samples. Kraemer [Evaluating medical tests. Objective and quantitative guidelines. 1992] used the level of test, Q, also known as “positive sign rate” (sum of true and false positives divided by sample size), to calculate quality sensitivity and specificity (QSN, QSP). These scaled indices may be more comparable across different patient samples, but have been little studied hitherto. Methods: The dataset of a pragmatic test accuracy study of the Mini-Addenbrooke’s Cognitive Examination (MACE) was re-interrogated to calculate values of QSN and QSP and other paired and unitary test outcome measures based on them, and comparison was made with outcomes previously calculated by standard methods. Results: QSN and QSP values in this cohort (n = 755; overall prevalence of dementia and mild cognitive impairment [MCI] 0.15 and 0.29, respectively) were inferior to Sens and Spec, as were all other outcome measures for MACE for the diagnosis of both dementia and MCI. QSN was relatively preserved, indicating the sensitivity of MACE. Conclusion: Indices of test outcome scaled according to Kraemer’s Q, the positive sign rate, are less impressive than outcomes calculated by standard methods. These discrepancies may have implications for test evaluation.
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Zuo, Lei, Ye Zhang, Maode Yan e Wenrui Ma. "Distributed Integrated Sliding Mode-Based Nonlinear Vehicle Platoon Control with Quadratic Spacing Policy". Complexity 2020 (24 dicembre 2020): 1–9. http://dx.doi.org/10.1155/2020/4949520.

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This paper investigates the nonlinear vehicle platoon control problems with external disturbances. The quadratic spacing policy (QSP) is applied into the platoon control, in which the desired intervehicle distance is a quadratic function in terms of the vehicle’s velocities. Comparing with the general constant time headway policy (CTHP), the QSP is more suitable to the human driving behaviors (HDB) and can improve the traffic capacity. Then, a novel platoon control scheme is proposed based on the distributed integrated sliding mode (DISM). Since the external disturbances are taken into consideration, the sliding mode method is employed to handle the disturbances. Moreover, the stability and string stability of the proposed platoon control system are strictly analyzed. In final, numerical simulations are provided to verify the proposed approaches.
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Lin, Lin, e Yu Tong. "Optimal polynomial based quantum eigenstate filtering with application to solving quantum linear systems". Quantum 4 (11 novembre 2020): 361. http://dx.doi.org/10.22331/q-2020-11-11-361.

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We present a quantum eigenstate filtering algorithm based on quantum signal processing (QSP) and minimax polynomials. The algorithm allows us to efficiently prepare a target eigenstate of a given Hamiltonian, if we have access to an initial state with non-trivial overlap with the target eigenstate and have a reasonable lower bound for the spectral gap. We apply this algorithm to the quantum linear system problem (QLSP), and present two algorithms based on quantum adiabatic computing (AQC) and quantum Zeno effect respectively. Both algorithms prepare the final solution as a pure state, and achieves the near optimal O~(dκlog⁡(1/ϵ)) query complexity for a d-sparse matrix, where κ is the condition number, and ϵ is the desired precision. Neither algorithm uses phase estimation or amplitude amplification.
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De Oliveira, Edna Castro, e Maria Geovana Melim Ferreira. "QUALIFICAÇÃO SOCIAL E PROFISSIONAL A PARTIR DA LÓGICA DOS MOVIMENTOS SOCIAIS DO CAMPO". Revista Inter Ação 44, n. 1 (13 maggio 2019): 164–79. http://dx.doi.org/10.5216/ia.v44i1.56120.

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O texto aborda resultados de pesquisa de mestrado realizada a partir da implementação do Programa ProJovem Campo Saberes da Terra (PJC-ST) no ES, voltado para a escolarização de camponeses com Qualificação Social e Profissional (QSP) na modalidade EJA. Tem como objetivo explicitar os desafios postos aos processos formativos no contexto do campo nas práticas de Educação Profissional. Toma como aportes teóricos a educação popular, os fundamentos e princípios da agroecologia e o trabalho como princípio educativo para o exercício da integração curricular. A metodologia da sistematização é assumida como forma de revisitar a prática e analisá-la criticamente. Os resultados indicam contribuições para o campo da política pública de EJA, tendo o diálogo de saberes, a alternância pedagógica e as práticas de QSP como elementos integradores do currículo.
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Shi, Shuangning, Yong Shang, Qinglin Liang e Bin Liang. "The Performance of QSP Beamformer with Array Errors". PIERS Online 3, n. 7 (2007): 1093–96. http://dx.doi.org/10.2529/piers061007112858.

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Mistry, Hitesh B. "QSP Versus the Rest: Let the Competition Commence!" CPT: Pharmacometrics & Systems Pharmacology 7, n. 8 (19 luglio 2018): 490. http://dx.doi.org/10.1002/psp4.12314.

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Purnomo, Rochmat Aldy. "Strategi Pengembangan Produk Kuliner Di Pusat Kuliner Pratistha Harsa Purwokerto". Jurnal Ekonomi 21, n. 1 (23 ottobre 2018): 91. http://dx.doi.org/10.24912/je.v21i1.384.

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This study aims to analyze the development strategy Pratistha Harsa Culinary Market. Collecting data using the techniques of interview, observation and literature. The respondents were selected ie Pratistha Harsa Chief Manager, Chairman of the Society Pratistha Harsha, traders culinary Pratistha Harsa. The population of merchants in Pratistha Harsa number of 65 peoples and a sample of 40 seller respondents. Selection of the sample using simple random sampling. This research using SWOT Matrix and QSP Matrix. The results showed that the development strategy for the culinary center Pratistha Harsa obtained from the SWOT Matrix and Matrix QSP is using WT strategy, namely to minimize weaknesses and avoid external threats. It can be concluded that the formulation of the strategy of development of the culinary center Pratistha Harsha, looking at strengths, weaknesses, opportunities and threats of Pratistha Harsa relocation program that decision makers in Pratistha Harsha will apply Weaknesess-Threats Strategy.
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Burke, John M., Anna Katharina Wilkins, Andrew Matteson, Lore Gruenbaum e Josh F. Apgar. "Computational exploration of mechanistic determinants of antibody drug-conjugate pharmacokinetics using quantitative systems pharmacology modeling strategies." Journal of Clinical Oncology 35, n. 15_suppl (20 maggio 2017): e14000-e14000. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14000.

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e14000 Background: The pharmacokinetics of antibody drug conjugate (ADC) therapeutics typically show a discrepancy between the PK of total antibody (conjugated and unconjugated antibody) and that of conjugated antibody, carrying one or more payload molecules This discrepancy is often attributed to deconjugation (Kamath, 2014), however recent evidence suggests that the underlying mechanisms may be more complex. Methods: This work employs a computational quantitative systems pharmacology (QSP) approach to understand the impact of drug antibody ratio (DAR) and the resulting changes in molecular properties on overall PK and relative payload disposition as observed in preclinical and clinical studies. Results: Using QSP approaches, the model (1) describes the kinetics of individual DAR species and agrees well with typical ADC PK, individual DAR PK, and average DAR measurements in vivo; (2), quantitatively describes the trade-off between higher DAR and lower exposure; consequently, we predict that ADC2 is half as potent as ADC4 and ADC8, which are equipotent; (3) longer mAb half-life reduces payload delivery after multiple doses; and (4) ADC half-life affects the percent of payload delivered through different mechanisms. Conclusions: A QSP model describing mechanism is a useful tool to translate and understand PK from preclinical species to human, by acting as a central repository of data, knowledge, and hypotheses. It provided a rational basis to generate testable hypotheses and provide early insights into complex ADC PK data and established the benefit of using computational models to design novel ADCs and to optimize the discovery and development of existing ADCs.
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Wicaksono, Istiko Agus, Isna Windani e Erny Erny. "Prioritas Strategi Pengembangan Serat Rami (Boehmeria nivea proper) Jenis Ina Grass di Kabupaten Wonosobo". Agroland: Jurnal Ilmu-ilmu Pertanian 28, n. 2 (2 settembre 2021): 197–203. http://dx.doi.org/10.22487/agrolandnasional.v28i2.806.

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Penelitian ini dilakukan untuk mengetahui prioritas strategi dalam pengembangan produk serat rami ina grass di Kabupaten Wonosobo. Informasi mengenai prioritas strategi ini merupakan salah satu komponen penting dalam menentukan kemajuan perkembangan produk dan mengembangkan potensi serat rami sebagai salah satu produk unggulan daerah khususnya di Kabupaten Wonosobo Provinsi Jawa Tengah. Metode yang digunakan dalam penelitian ini adalah analisis deskriptif dengan pendekatan secara kualitatif untuk mengekplorasi permasalahan dari segi faktor internal eksternal dan memetakan prioritas strategi dari beberapa alternatif strategi yang terkait. Eksplorasi dilakukan dengan cara wawancara mendalam terhadap tiga orang informan kunci dan wawancara terstruktur terhadap enam orang informan pendukung. Analisis data dalam penelitian ini menggunakan alat analisis Matriks QSP (Quantitative Strategic Planning). Secara garis besar hasil studi yang didapatkan dari hasil Matrix QSP diperoleh tiga strategi yang mempunyai nilai tertinggi yaitu memberikan pelatihan terhadap tenaga kerja agar lebih terampil, menggunakan teknologi modern dan meningkatkan promosi produk jadi dari serat rami ina grass agar dikenal oleh masyarakat luas.
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Rachman, Nadya Megawati. "Analisis Strategi Pusat Pendidikan dan Pelatihan Perdagangan Menuju Corporate University". Cendekia Niaga 3, n. 2 (29 novembre 2019): 12–28. http://dx.doi.org/10.52391/jcn.v3i2.484.

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In order to increase the capacity and quality of human resources at the Ministry of Trade, the Center for Trade and Education has an important role in supporting the achievement of the vision and mission and the application of organizational cultural values of the Ministry of Trade. Innovations in the learning process must be implemented in the face of the demands of globalization and the times. The purpose of this study is to analyze the Strategic Center of Trade Training and Education towards Corporate University. The analytical method used in this study is to use IFE-EFE matrix analysis, IE matrix, SWOT analysis and Qualitative Strategic Planning (QSP) matrix. Based on the results of the analysis conducted by the Trade Training Center, it is expected to implement the S-O strategy, namely strengthening the implementation of learning organizations with the Visionary Leadership approach as the main priority strategy generated from the QSP matrix analysis. Keywords : Corporate University, IFE-EFE matrix, IE matrix, SWOT, QSPM
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Bihorel, Shihem. "SC3.3 - Therapeutic area case study: QSP in immuno-oncology". Drug Metabolism and Pharmacokinetics 35, n. 1 (2020): S3. http://dx.doi.org/10.1016/j.dmpk.2020.04.279.

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Gadkar, Kapil. "SC3.4 - Therapeutic area case study: QSP in inflammatory disease". Drug Metabolism and Pharmacokinetics 35, n. 1 (2020): S3—S4. http://dx.doi.org/10.1016/j.dmpk.2020.04.280.

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Akbar Nugraha, Muhammad Kemalvin. "Strategy of Ciplukan Fruit Agribusiness Development (Physalis peruviana) At Waaida Farm, West Java". AGRIFOR 17, n. 1 (11 marzo 2018): 131. http://dx.doi.org/10.31293/af.v17i1.3358.

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Waaida Farm is a pioneer company of agribusiness of Physalis peruviana “ciplukan” in Indonesia. Waaida Farm started its cultivation of “ciplukan” with the considerations of “ciplukan” that has a big market opportunity. However, Waaida Farm could just fulfill the demand from Java so far because of its low production. The object of this research is to give a solution regarding the agribusiness developing strategy of “ciplukan” based on internal and external factors analysis which can be done at Waaida Farm. This research uses descriptive-qualitative design and study case research technique. Data collecting method used in this research is through interview and literature study. In needs to find the right developing strategy, there needs to be a matrix analysis of IFAS, EFAS, IE, SWOT and QSP. The SWOT analysis resulted five strategy formulations that can be implemented at Waaida Farm. The matrix QSP analysis resulted the right priority strategy for Waaida Farm, that is to invest the company’s profit for purchasing cooler boxes to overcome production shortages in certain periods and to increase the number of sales.
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Le Sauteur-Robitaille, Justin, Zhe Si Yu e Morgan Craig. "Impact of estrogen population pharmacokinetics on a QSP model of mammary stem cell differentiation into myoepithelial cells". AIMS Mathematics 6, n. 10 (2021): 10861–80. http://dx.doi.org/10.3934/math.2021631.

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<abstract> <p>Stem cell differentiation cascades are critical components of healthy tissue maintenance. Dysregulation in these systems can lead to serious diseases, including cancer. Myoepithelial mammary cells are produced from differentiated mammary stem cells in processes regulated, in part, by estrogen signalling and concentrations. To quantify and predict the production of mammary myoepithelial cell production by estrogen, we developed a mechanistic, quantitative systems pharmacology (QSP) model that includes the explicit characterization of free and unbound estrogen concentrations in circulation. Linking this model to a previously developed population pharmacokinetics model for ethinyl estradiol, a synthetic form of estrogen included in oral contraceptives, we predicted the effects of estrogen on myoepithelial cell development. Interestingly, pharmacokinetic intraindividual variability alone did not significantly impact on our modelos predictions, suggesting that combinations of physiological and pharmacokinetic variability drive heterogeneity in mechanistic QSP models. Our model is one component of an improved understanding of mammary myoepithelial cell production and development, and our results support the call for mechanistically constructed systems models for disease and pharmaceutical modelling.</p> </abstract>
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Ribba, B., HP Grimm, B. Agoram, MR Davies, K. Gadkar, S. Niederer, N. van Riel, J. Timmis e PH van der Graaf. "Methodologies for Quantitative Systems Pharmacology (QSP) Models: Design and Estimation". CPT: Pharmacometrics & Systems Pharmacology 6, n. 8 (11 luglio 2017): 496–98. http://dx.doi.org/10.1002/psp4.12206.

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Hosseini, Iraj, Justin Feigelman, Anita Gajjala, Monica Susilo, Vidya Ramakrishnan, Saroja Ramanujan e Kapil Gadkar. "gQSPSim: A SimBiology‐Based GUI for Standardized QSP Model Development and Application". CPT: Pharmacometrics & Systems Pharmacology 9, n. 3 (marzo 2020): 165–76. http://dx.doi.org/10.1002/psp4.12494.

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Au-Yong, Cheong Peng, Azlan Shah Ali e Faizah Ahmad. "Enhancing building maintenance cost performance with proper management of spare parts". Journal of Quality in Maintenance Engineering 22, n. 1 (14 marzo 2016): 51–61. http://dx.doi.org/10.1108/jqme-01-2015-0001.

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Purpose – Scheduled building maintenance requires appropriate and adequate spare parts to replace existing parts on a regular basis. Management of spare parts is seen as an important criterion to ensure the efficiency of scheduled maintenance. The purpose of this paper is to identify the contributors of spare parts management and investigate the relationship between these contributors and maintenance cost performance. Design/methodology/approach – This research adopted a quantitative approach, which utilised questionnaire surveys to study the relationship between the contributors of spare parts management and maintenance cost performance. The data were analysed through descriptive analysis, correlation, and regression analysis. Additionally, a case study was examined to validate the results obtained from the survey. Findings – The results of this research demonstrated that the quality of spare parts (QSP), budget allocation for acquisition of spare parts, and level of stocks were significantly correlated to the maintenance cost variance (MCV). Moreover, the results of the regression analysis indicated that the QSP was the significant predictor of MCV. Originality/value – This research highlights the importance of spare parts management in building maintenance. It recommends that maintenance management set up a spare parts management department for updating stocks frequently. Meanwhile, the management should avoid ad-hoc acquisition of spare parts, as this is always more expensive. The management should also select spare parts based on quality instead of lowest cost. In addition, building managers should also apply the developed regression model in practice to predict and improve maintenance performance.
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Rienaya, Cindya, Mudatsir Najamuddin e Akhmad Mahbubi. "STRATEGI BISNIS KOPI MEREK COFFESSO PT DAVID ROY INDONESIA". AGRIBUSINESS JOURNAL 10, n. 1 (25 gennaio 2021): 83–94. http://dx.doi.org/10.15408/aj.v10i1.9215.

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Penelitian ini bertujuan untuk menentukan strategi bisnis yang cocok untuk PT.David Roy Indonesia. Matriks IFE, EFE, SWOT, dan QSPM digunakan untukmenganalisis data. Hasil dari matriks IFE menunjukkan bahwa kekuatan utamaperusahaan adalah visi perusahaan dengan skor 0,486 dan kelemahan utamaadalah lokasi pabrik dengan skor 0.280. Selain itu, hasil dari matriks EFEmenunjukkan bahwa peluang utama adalah kebijakan pemerintah yang terkaitdengan ekspor biji kopi dengan skor 0,397, dan ancaman utama adalah kebijakanpemerintah yang berkaitan dengan impor kopi olahan dengan skor 0,266. AnalisisSWOT menghasilkan beberapa alternatif strategi dan matriks QSP menunjukkanbahwa strategi diferensiasi mendapatkan prioritas tertinggi.
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Nayak, Satyaprakash, Dooyoung Lee, Steven Arkin, Steven W. Martin, Anne C. Heatherington, William S. Denney, Paolo Vicini e Fei Hua. "A Quantitative Systems Pharmacology Model for the Coagulation Network Describes Biomarker Changes Observed in a Clinical Study with FXa Variant and Predicts Age-Associated Biomarker Variations". Blood 126, n. 23 (3 dicembre 2015): 3502. http://dx.doi.org/10.1182/blood.v126.23.3502.3502.

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Abstract It is known that the coagulation factor levels change with age. In this work, we have applied a quantitative systems pharmacology (QSP) model of the coagulation network to predict whether age related changes in coagulation factor levels will impact dose response for PF-05320907 on various pharmacodynamic endpoints. PF-05230907 (PF-907) is a variant of FXa, in which the conformational transition from zymogen to active protease is impaired. Binding to activated factor V facilitates its transition to the active conformation, rescues procoagulant activity and is hypothesized to localize PF-907 hemostatic effect to sites of hemorrhage. It is currently in development for the indication of intracerebral hemorrhage (ICH). Pharmacokinetic (PK) and pharmacodynamic (PD) data are available from the healthy subjects phase 1 study of single dose escalation of intravenous bolus infusion of PF-907. The next study for PF-907 will be conducted in ICH patients, who will have a much higher median age than the median age in the healthy subjects in the Phase 1 study. Our group has implemented a QSP model for the coagulation network to enable integrated understanding of all the data and underlying pharmacology1. The model has been optimized to describe in vitro biomarker changes including; thrombin generation assay (TGA), activated partial thromboplastin time (aPTT) and prothrombin time (PT) as well as in vivo biomarker changes including prothrombin fragment 1+2 (PF1+2), thrombin-anti-thrombin III complex (TAT) and D-dimer. In this simulation study, we used the model to first describe biomarker changes with treatment of FXa variant in hemostatic normal subjects and then used model simulations to predict the behavior of important biomarkers in an older ICH population. A single compartment PK model for PF-907 was first established to describe the PK data obtained from the phase 1 study. The PK model was then combined with the QSP model to predict biomarker changes following PF-907 treatment. Comparison with observed clinical data showed that the model adequately predicted dose-dependent change in TGA parameters, aPTT, PF1+2, TAT and D-dimer. In addition, the model also predicted that there would be no change in PT, which was consistent with observed first in human results with the PF-907 treatment. After model validation using FIH data, the model was then used to predict biomarker changes for older subjects using literature reported changes in baseline levels of coagulation factors for subjects over a period of 40 years. The simulation predicted minimal shifts in the PD responses suggesting that the dose-response to PF-907 may not change significantly between young and older populations. The model, however, did not consider other characteristics beyond coagulation factor level changes in older populations, which may impact the safety profile of PF-907 treatment. In summary, this study indicates that it is possible to predict the response of a hemostatic agent with a QSP model. Following validation, the model can also extrapolate from a standard subject to new patient populations and indicates that no dose adjustment due to age is required. Reference 1. Nayak, S., Lee, D., Patel-Hett, S., Pittman, D., Martin, S., Heatherington, A., Vicini, P. and Hua, F. (2015), Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers. CPT: Pharmacometrics & Systems Pharmacology. doi:10.1002/psp4.50 Disclosures Nayak: Pfizer Inc: Employment. Lee:Pfizer Inc.: Employment. Arkin:Pfizer Inc: Employment. Martin:Pfizer Inc: Employment. Heatherington:Pfizer Inc.: Employment. Denney:Pfizer Inc.: Employment. Vicini:Pfizer Inc.: Employment. Hua:Pfizer Inc: Employment.
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Paredes Bonilla, Rosalba Vivian, Fahima Nekka e Morgan Craig. "A Quantitative Systems Pharmacology Framework for Optimal Doxorubicin Granulocyte Colony-Stimulating Factor Regimens in Triple-Negative Breast Cancer". Pharmacology 106, n. 9-10 (2021): 542–50. http://dx.doi.org/10.1159/000518037.

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<b><i>Introduction:</i></b> To mitigate the risk of neutropenia during chemotherapy treatment of triple-negative breast cancer, prophylactic and supportive therapy with granulocyte colony-stimulating factor (G-CSF) is administered concomitant to chemotherapy. The proper timing of combined chemotherapy and G-CSF is crucial for treatment outcomes. <b><i>Methods:</i></b> Leveraging our established mathematical model of neutrophil production by G-CSF, we developed quantitative systems pharmacology (QSP) framework to investigate how modulating chemotherapy dose frequency and intensity can maximize antitumour effects. To establish schedules that best control tumour size while minimizing neutropenia, we combined Gompertzian tumour growth with pharmacokinetic/pharmacodynamic models of doxorubicin and G-CSF, and our QSP model of neutrophil production. <b><i>Results:</i></b> We optimized a range of chemotherapeutic cycle lengths and dose sizes to establish regimens that simultaneously reduced tumour burden while minimizing neutropenia. Our results suggest that cytotoxic chemotherapy with doxorubicin 45 mg/m<sup>2</sup> every 14 days provides effective control of tumour growth while mitigating neutropenic risks. <b><i>Conclusion:</i></b> This work suggests future avenues for optimal regimens of chemotherapy with prophylactic G-CSF support. Importantly, the algorithmic approach that we developed can aid in balancing the anticancer and the neutropenic effects of both drugs, and therefore contributes to rational considerations in clinical decision-making in triple-negative breast cancer.
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Burris, Howard A., Margaret K. Callahan, Anthony W. Tolcher, Shivaani Kummar, Gerald Steven Falchook, Russell Kent Pachynski, Scott S. Tykodi et al. "Phase 1 safety of ICOS agonist antibody JTX-2011 alone and with nivolumab (nivo) in advanced solid tumors; predicted vs observed pharmacokinetics (PK) in ICONIC." Journal of Clinical Oncology 35, n. 15_suppl (20 maggio 2017): 3033. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.3033.

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3033 Background: JTX-2011 is an agonist monoclonal antibody that targets ICOS, Inducible CO-Stimulator of T cells. A dual mechanism of action is intended to activate antigen-specific CD4 T effector cells and selectively deplete intratumoral T regulatory cells. JTX-2011 is equally potent across human, rodent, and non-human primate species. Methods: A quantitative systems pharmacology (QSP) model describing target binding by JTX-2011 and target mediated drug disposition in blood, tumor and non-tumor tissues was based on preclinical potency and non-linear PK data across species. The model was translated to predict PK and target engagement (TE) in humans to facilitate dose selection. The QSP model predicts > 95% TE for 21 days at the top planned dose. We present safety and actual/predicted PK from a Phase 1 study of JTX-2011 alone (Part A) and safety in combination with nivo (Part B). Results: 25 subjects have been dosed, 19 in 4 cohorts of JTX-2011 alone at .003, .01, .03, and .1 mg/kg IV q 21 days, and 6 in 2 cohorts of JTX-2011 .01 mg/kg and .03 mg/kg IV plus nivo 240 mg IV q21 days. Safety data from ≥ 1 cycle is available for 12 subjects in Part A (7 ≥ 3 cycles), and 3 in Part B (all ≥ 3 cycles). PK data is available for cycle 1 of Part A. Mean age (±SD) is 60 (±10.6). Mean prior systemic therapies is > 5 (range 1-11). Tumor types include endometrial, triple negative breast, melanoma, lung, pancreatic and colorectal cancers. No dose limiting toxicities have been reported. 3 Grade 3 adverse events (AEs) were reported in 2 Part A subjects: anemia and hypoxia (unrelated SAE) at .003 mg/kg and JTX-2011 related diarrhea at .1 mg/kg. Grade 1-2 AEs in ≥2 subjects are chills, pyrexia, neck pain, dizziness, and nausea. 5 subjects had JTX-2011 related Grade 1-2 infusion reactions up to 6 hours post infusion. Non-linear exposure increase was observed. While PK at lower doses is consistent with model predictions, AUC and t1/2at 0.03 and 0.1 mg/kg doses are higher than predicted, suggesting higher than predicted TE. Conclusions: JTX-2011 has been well tolerated up to 0.1 mg/kg and with nivo at .01 mg/kg IV q 21 days. Greater than linear exposure increase was observed and TE may be higher than QSP model prediction. Clinical trial information: NCT02904226.
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Kierzek, Andrzej. "SC3.5 - Tutorial: How to build a QSP model in less than one hour". Drug Metabolism and Pharmacokinetics 35, n. 1 (2020): S4. http://dx.doi.org/10.1016/j.dmpk.2020.04.281.

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Imron, Tubagus, Rizal Syarief Sjaiful Nazli e Sapta Raharja. "Strategi Pengembangan Pemasaran Batu Andesit (Studi Kasus pada PT Duta Keluarga Imfaco, Bogor Jawa Barat)". MANAJEMEN IKM: Jurnal Manajemen Pengembangan Industri Kecil Menengah 13, n. 2 (3 gennaio 2019): 127. http://dx.doi.org/10.29244/mikm.13.2.127-136.

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<p>Andesite stone mining activities in Bogor area is now growing, one of the andesite stone processing business is PT Duta Keluarga Imfaco located in Bogor Regency, West Java. The economically valuable andesit stone is expected to be the mainstay of the income of the surrounding community, characterized by the increasing market demand and the growing interest of the community towards andesite stone. The purpose of this study are (1) to identify internal and external factors of PT Imfaco Family Ambassador; (2) Developing appropriate market development strategies; and (3) Develop alternative strategies of andesite stone marketing development. The study used descriptive and analytic methods that are case studies. Determination of respondents with purposive sampling method, with consideration that mastered the problems to be asked. Data analysis with IFE and EFE matrix to identify internal and external factor of company, then mapping with IE matrix, to see company position. Preparation of strategy with SWOT matrix, yield several alternative strategies that can be implemented. The final stage with the QSP matrix, to determine the priority of the most appropriate strategy to be implemented. Based on the results of IFE and EFE matrix analysis, indicates the company is in a stable position in responding to external situations. The result of analysis with IE matrix, company is in quadrant V, that is growth and stability, where strategy that can be done is market penetration and business development. Results of analysis with SWOT matrix obtained alternative strategies that can be implemented and with the QSP matrix obtained the most appropriate strategy to be implemented in order to develop the company's marketing strategy is to expand the marketing network.</p>
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Widuri, Bambang, Amiruddin Saleh e Nurheni Sri Palupi. "Kelayakan dan Strategi Pengembangan Usaha pada Outlet Ayam Goreng Waralaba dan Mandiri". MANAJEMEN IKM: Jurnal Manajemen Pengembangan Industri Kecil Menengah 9, n. 2 (2 dicembre 2014): 179–94. http://dx.doi.org/10.29244/mikm.9.2.179-194.

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The key to the success of small and medium enterprises located in the possession of knowledge, courage and sincerity in running the business. Currently, in order to minimize the risks that may arise, many small businesses, especially entrepreneurs, using the franchise system (franchise) as a means to develop their business. Failure in business franchise can be traced through several aspects, namely finance, management and marketing aspects. The purposes of the study are: (1) to describe the feasibility of fried chicken business with franchise and independent system, (2) to describe the perception of consumers towards the products of fried chicken business with franchise and independent system, (3) to develop appropriate strategies for developing franchise and/or independent system. The study was conducted at franchised/independent outlet located Bogor regency. Respondent has been collected by purposive sampling with 124 respondens. The experiment was conducted from February to March 2012. Kind of data processing technique we used was Net Present Value (NPV), Internal Rate of Return (IRR), Net Benefit Cost Ratio (Net B / C), Payback Period (PBP), Internal Factor Evaluation (IFE), External Factor Evaluation (EFE), Internal-External (IE), Strength, Weaknesses, Opportunities and Threats (SWOT) and Quantitative Strategic Planning (QSP) analysis system. Based on feasibility analysis, both fried chicken business with franchise and independent systems are feasible to be implemented. Franchise system offers more opportunity to get higher and faster returns, as well as to reach PBP faster than independent system. Furthermore, fried chicken business with franchise system shall be easier to get the trust of consumers because that system is more practical and besides, that system also offers cheaper price which will drive someone to reach PBP and return on capital faster. The reason of consumer to buy product are price, practice, and higiene. Based on the results of the matrix QSP fried chicken franchise, earned the most interesting strategy to be applied is to maintain customer loyalty, while independent business is improving the quality of products and services.The key to the success of small and medium enterprises located in the possession of knowledge, courage and sincerity in running the business. Currently, in order to minimize the risks that may arise, many small businesses, especially entrepreneurs, using the franchise system (franchise) as a means to develop their business. Failure in business franchise can be traced through several aspects, namely finance, management and marketing aspects. The purposes of the study are: (1) to describe the feasibility of fried chicken business with franchise and independent system, (2) to describe the perception of consumers towards the products of fried chicken business with franchise and independent system, (3) to develop appropriate strategies for developing franchise and/or independent system. The study was conducted at franchised/independent outlet located Bogor regency. Respondent has been collected by purposive sampling with 124 respondens. The experiment was conducted from February to March 2012. Kind of data processing technique we used was Net Present Value (NPV), Internal Rate of Return (IRR), Net Benefit Cost Ratio (Net B / C), Payback Period (PBP), Internal Factor Evaluation (IFE), External Factor Evaluation (EFE), Internal-External (IE), Strength, Weaknesses, Opportunities and Threats (SWOT) and Quantitative Strategic Planning (QSP) analysis system. Based on feasibility analysis, both fried chicken business with franchise and independent systems are feasible to be implemented. Franchise system offers more opportunity to get higher and faster returns, as well as to reach PBP faster than independent system. Furthermore, fried chicken business with franchise system shall be easier to get the trust of consumers because that system is more practical and besides, that system also offers cheaper price which will drive someone to reach PBP and return on capital faster. The reason of consumer to buy product are price, practice, and higiene. Based on the results of the matrix QSP fried chicken franchise, earned the most interesting strategy to be applied is to maintain customer loyalty, while independent business is improving the quality of products and services.
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46

Sahasranaman, Srikumar, Oleg Demin, Dmitry Shchelokov, Veronika Musatova, Nageshwar Budha e Ying Ou. "A Quantitative Systems Pharmacology (QSP) Model to Predict Receptor Occupancy of Bruton's Tyrosine Kinase (BTK) Inhibitors in Peripheral Blood Mononuclear Cells, Bone Marrow and Lymph Nodes of Patients with B-Cell Malignancies". Blood 134, Supplement_1 (13 novembre 2019): 1289. http://dx.doi.org/10.1182/blood-2019-129133.

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Abstract (sommario):
Background: Bruton tyrosine kinase (BTK) is a key component of the B-cell receptor signaling pathway. The BTK inhibitors ibrutinib and acalabrutinib have been approved for the treatment of various B-cell malignancies. Zanubrutinib is a potent and highly specific next-generation BTK inhibitor currently in Phase 3 clinical testing. Achieving complete and sustained target engagement with respect to BTK receptor occupancy is thought to be an important factor for attaining deeper and durable clinical responses with the BTK inhibitors. Testing for BTK occupancy in peripheral blood mononuclear cells (PBMC) can be assessed in clinical studies. However, it is difficult to sample deep target tissues such as bone marrow (BM) and lymph nodes (LN) in patients to assess receptor occupancy. The objectives of this work were (1) to develop a QSP model to describe and predict the BTK receptor occupancy in PBMC, BM and LN after dosing with these BTK inhibitors in patients with B-cell malignancies, (2) to understand the impact of different dosing regimens (once daily (QD) v/s twice daily (BID)) on BTK receptor occupancy. Methods: A mathematical model was developed that describes: (1) pharmacokinetics (PK) of BTK inhibitors; (2) intracellular concentration of BTK inhibitors in PBMC, BM and LN; (3) binding of BTK inhibitors with BTK including competition with ATP and (4) BTK degradation/turnover rate. This QSP model includes ibrutinib with its metabolite PCI-45227, acalabrutinib with its metabolite ACP-5862, and zanubrutinib. Previously developed minimal Physiologically-based Pharmacokinetic (PBPK) models were used to reproduce PK of BTK inhibitors. Intracellular concentrations of BTK inhibitors were described in the model in accordance with PBPK equations for small molecules (Rodgers and Rowland. J Pharm Sci. 2006) and on the basis of their physico-chemical properties. Parameters and interindividual variability in parameter values were taken from previously developed models and estimated using experimental data. Sensitivity analyses using key model parameters such as BTK degradation/turnover rate were performed. The model was validated using available in vitro and clinical data on BTK occupancy. Results: The QSP model accurately described the observed clinical data on PK of BTK inhibitors during treatment with different doses and regimens of ibrutinib, acalabrutinib and zanubrutinib. There was good agreement between model prediction and observed BTK occupancy in PBMC and LN (Figure 1 and Figure 2). Zanubrutinib (160 mg BID) was predicted to result in higher median BTK occupancy with less variability in both PBMC and LN than ibrutinib (420 mg QD, 560 mg QD) and acalabrutinib (100 mg BID). In the absence of clinical BTK occupancy data in BM, the model predicted that steady-state trough BTK occupancy in BM were also predicted to be higher after zanubrutinib 160 mg BID administration, than those after ibrutinib 560 mg or 420 mg QD administration, and after acalabrutinib 100 mg BID administration. These differences are attributed to the PK properties (higher AUC and fraction unbound in plasma), binding properties to BTK (Kd, inactivation rate constant), and higher lipophilicity for zanubrutinib. The model predicted that 160 mg BID of zanubrutinib resulted in higher median trough BTK occupancy than 320 mg QD with less variability which is consistent with the observed clinical data (Figure 3). Conclusions: A QSP model was successfully developed and validated, which predicted higher median BTK occupancy with less variability for zanubrutinib in PBMC, BM and LN than ibrutinib and acalabrutinib. A BID dosing regimen produces higher BTK occupancy than a QD regimen over the dosing interval. Ongoing clinical trials with 160 mg BID zanubrutinib will help to determine if improved BTK occupancy in these peripheral and deep target tissues translate into improvements in clinical outcomes. Disclosures Sahasranaman: BeiGene: Employment, Equity Ownership. Demin:BeiGene USA, Inc.: Consultancy; InSysBio LLC: Employment. Shchelokov:InSysBio LLC: Employment; BeiGene USA, Inc.: Consultancy. Musatova:BeiGene USA, Inc.: Consultancy; InSysBio LLC: Employment. Budha:BeiGene Ltd.: Employment, Equity Ownership. Ou:BeiGene: Employment.
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47

Cheng, Yougan, Craig J. Thalhauser, Shepard Smithline, Jyotsna Pagidala, Marko Miladinov, Heather E. Vezina, Manish Gupta, Tarek A. Leil e Brian J. Schmidt. "QSP Toolbox: Computational Implementation of Integrated Workflow Components for Deploying Multi-Scale Mechanistic Models". AAPS Journal 19, n. 4 (24 maggio 2017): 1002–16. http://dx.doi.org/10.1208/s12248-017-0100-x.

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48

Stein, Andrew M., e Michael Looby. "Benchmarking QSP Models Against Simple Models: A Path to Improved Comprehension and Predictive Performance". CPT: Pharmacometrics & Systems Pharmacology 7, n. 8 (agosto 2018): 487–89. http://dx.doi.org/10.1002/psp4.12311.

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49

Fan, Subing, Jie Tuo, Dan Wang, Jingya Rong, Jianli Zhang, Qingxiang Ma, Xinhua Gao, Guohui Yang, Tiansheng Zhao e Noritatsu Tsubaki. "Facile Synthesis of Proton‐Type ZSM‐5 by Using Quasi‐Solid‐Phase (QSP) Method". Chemistry – A European Journal 26, n. 39 (17 giugno 2020): 8532–35. http://dx.doi.org/10.1002/chem.202002021.

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50

Goudarzi, Kiane, e Marcel Guenoun. "Conceptualisation et mesure de la qualité des services publics (qsp) dans une collectivité territoriale". Politiques et Management Public, Vol 27/3 (15 giugno 2012): 31–54. http://dx.doi.org/10.4000/pmp.2986.

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