Model For Evaluation Of Response Research Articles

A Delta-radiomics model for preoperative evaluation of Neoadjuvant chemotherapy response in high-grade osteosarcoma

BackgroundThe difficulty of assessment of neoadjuvant chemotherapeutic response preoperatively may hinder personalized-medicine strategies that depend on the results from pathological examination.MethodsA total of 191 patients with high-grade osteosarcoma (HOS) were enrolled retrospectively from November 2013 to November 2017 and received neoadjuvant chemotherapy (NCT). A cutoff time of November 2016 was used to divide the training set and validation set. All patients underwent diagnostic CTs before and after chemotherapy. By quantifying the tumor regions on the CT images before and after NCT, 540 delta-radiomic features were calculated. The interclass correlation coefficients for segmentations of inter/intra-observers and feature pair-wise correlation coefficients (Pearson) were used for robust feature selection. A delta-radiomics signature was constructed using the lasso algorithm based on the training set. Radiomics signatures built from single-phase CT were constructed for comparison purpose. A radiomics nomogram was then developed from the multivariate logistic regression model by combining independent clinical factors and the delta-radiomics signature. The prediction performance was assessed using area under the ROC curve (AUC), calibration curves and decision curve analysis (DCA).ResultsThe delta-radiomics signature showed higher AUC than single-CT based radiomics signatures in both training and validation cohorts. The delta-radiomics signature, consisting of 8 selected features, showed significant differences between the pathologic good response (pGR) (necrosis fraction ≥90%) group and the non-pGR (necrosis fraction < 90%) group (P < 0.0001, in both training and validation sets). The delta-radiomics nomogram, which consisted of the delta-radiomics signature and new pulmonary metastasis during chemotherapy showed good calibration and great discrimination capacity with AUC 0.871 (95% CI, 0.804 to 0.923) in the training cohort, and 0.843 (95% CI, 0.718 to 0.927) in the validation cohort. The DCA confirmed the clinical utility of the radiomics model.ConclusionThe delta-radiomics nomogram incorporating the radiomics signature and clinical factors in this study could be used for individualized pathologic response evaluation after chemotherapy preoperatively and help tailor appropriate chemotherapy and further treatment plans.

Driving Simulator for Electric Vehicles Using the Markov Chain Monte Carlo Method and Evaluation of the Demand Response Effect in Residential Houses

It is essential to secure flexible resources in power systems to increase the proportion of variable renewable energy generation systems. One flexible resource is demand response (DR) of the batteries of electric vehicles (EVs). In this study, we propose an electric vehicle driving simulator using the Markov chain Monte Carlo (MCMC) method and an EV demand response evaluation model. The former is a highly versatile EV driving simulator that can produce a random driving pattern based on actual EV fleet data, taking into account various features. The latter is a residential DR evaluation model that minimizes a household electricity bill based on the simulated fleet data and enables realistic DR operation using three processes: forecasting, planning, and operation. The contribution of this paper is to enable evaluation of realistic EV battery value in various housing and EV utilization combinations. We found that the EV battery control provides an economic benefit of US$62 (5% of the night-charging case cost) with only charge control and US$370 (31%) with charge and discharge control, as the average expected value based on our assumption of evaluation. Because 40-kWh EV batteries have a sufficiently large capacity to store surplus power from a rooftop PV, they can be operated by determining the operation schedule based on a fixed-fee structure without forecasting or planning.

A Multi-Perspective Model for Evaluation of Residential Thermal Demand Response

Demand response (DR) is envisaged to be of significance for enhancing the flexibility of power systems. The distributed nature of residential demand-side resources necessitates the introduction of an aggregator/retailer to represent the flexible demand in the electricity market. However, the objectives of the residential consumers, the retailer, and the system operator might not be aligned. This paper presents a multi-perspective model which integrates the optimization problems of these strategic decision makers within a single framework for evaluation of residential thermal DR. The multi-perspective model is formulated as a bilevel optimization problem and incorporates detailed building state-space models of residential thermal demand. Comparison of the multi-perspective model with existing market-based models shows that it is able to provide a holistic view of residential DR by capturing the interactions in both the retail and wholesale markets. The results also show that centralized optimization models would over-estimate the system value of DR in the presence of strategic market participants. Detailed sensitivity analyses using the multi-perspective model reveal interesting insights on the welfare distribution aspects of DR. The results show that in addition to consumers’ flexibility, retail contract design will also play a major role in determining the welfare distribution among the involved entities.

Abstract 4984: Development of an improved humanized patient-derived xenograft, Hu-PDX, mouse model for evaluation of antitumor immune response in lung cancer

Abstract Current preclinical models of non-small cell lung cancer (NSCLC) do not recapitulate the human tumor microenvironment. Mice reconstituted with a human immune system and bearing human patient derived xenografts may be advantageous in evaluating human anti-tumor immune response. We developed an improved NOD scid gamma (NSG) mouse model derived from non-expanded CD34+ stem cells, without CD3+ T cell contamination, to evaluate antitumor responses to immunotherapy in NSCLC. Using fresh CD34+ from umbilical cord blood reduced humanization time significantly. Human CD45+ cell reconstitution with increased functional human lymphoid (B, T, monocytes and NK cells) and myeloid (macrophages and MDSCs) lineage repopulation, without the onset of GvHD, was achieved as early as 4 weeks post-stem cell engraftment. Published studies using expanded CD34+ derived humanization reveal compromised purity of CD34+ stem cells with an increasing number of mononuclear cells. Reconstitution of CD8+ and CD4+T cells is not achieved until 12 to 15 weeks post-engraftment at much lower levels than fresh CD34+ humanization. Single cell suspension analysis shows levels of human reconstituted T, B, NK, DC and MDSC cells at 4 weeks, which increased significantly at 6 and 9 weeks in peripheral blood, spleen and bone marrow. Human repopulated T cells were functionally active in secretion of IFN-γ by mitogenic stimuli such as PMA and IL-2 and by allogenic human cancer cells. Antigen specific CTL responses were observed when reconstituted human T cells from PDX bearing humanized mice were challenged with PDX tumor. No non-antigen specific responses were observed when T cells were co-cultured with HLA-matched human bronchial epithelial cells (HBEC). To evaluate the applicability of the humanized mouse in lung cancer translational research, we combined it with Hu-PDX or Hu-xenograft tumors and analyzed tumor growth and treatment response to the anti-PD1 checkpoint inhibitor pembrolizumab. We found that efficient engraftment of PDXs and xenograft tumors were not dependent on donor HLA-status. Similar to the clinical outcome, treatment with pembrolizumab, inhibited tumor growth significantly in both Hu-PDX, and Hu-xenograft mice regardless of donor HLA-types, increasing cytotoxic T cells and decreasing MDSC levels. Pembrolizumab had no effect on the non-humanized NSG controls. In concordance with our previous study with a syngeneic mouse tumor, the antitumor effect of check point blockade was significantly enhanced when combined with nanoparticle systemically deliveredTUSC2, a tumor suppressor and immunomodulatory gene, in a KRAS mutant lung metastasis humanized mouse model. In conclusion, fresh CD34+ are more effective than their expanded counterparts in humanizing mice, do so in much reduced time, and recapitulate the immune response to cancer. Citation Format: Ismail M. Meraz, Mourad Majidi, Feng Meng, RuPing Shao, Min Jin Ha, Shinya Neri, Bingliang Fang, Steven H. Lin, Peggy T. Tinkey, Elizabeth J. Shpall, Jeffrey Morris, Jack A. Roth. Development of an improved humanized patient-derived xenograft, Hu-PDX, mouse model for evaluation of antitumor immune response in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4984.

An educational-evaluation study for street children in Rumah Impian Foundation

This research aims to evaluate the education of street children at Rumah Impian Foundation in Yogyakarta. This is an evaluation research using a responsive evaluation model with a naturalistic qualitative approach. The evaluation stages carried out in this study consist of Rational, Anteccendent, Transaction, and Outcome. The sampling technique used was purposive sampling with snowball sampling because the data were obtained from the community of the subjective sample, or in other words, the sample used is very rare and is grouped in a set. The data were analyzed using qualitative analysis techniques by Milles and Huberman. The results of the study show that, at the rational stage, the background of the educational concern for street children starts with a sense of caring about the street children’s future that is worth fighting for. In the antecedent stage, there is a conformity input between the volunteer, apprenticeship membership, and the street children’s education needs, in the form of policies and recruiting volunteers to be a companion to street children. At the transaction stage, the process between the foundation and street children education is appropriate, meaning that the foundation has facilitated the education needed by street children both formally and non-formally, in the form of increasing their skills through courses. Thus, there is a match between what was done in the previous stages and its results, showing that there are street children who reach their dreams, as a result of the foundation's efforts to continue knitting their dreams through intensive activities and assistance.

EVALUATING ENTREPRENEURSHIP TRAINING PROGRAM FOR KEAKSARAAN FUNGSIONAL PROGRAM AT KECAMATAN GUNUNGHALU

Keaksaraan Fungional (KF) program faces challenges for its participants still face issues post-program, specifically economic welfare related issues. Various programs have been organised to supplement KF. Among them, is entrepreneurship training and life skills training. This research attempts to evaluate such program held at Desa Pandansari, Kecamatan Gununghalu, specifically at the community of Karya Lestari Community Learning Center (CLC) using the responsive evaluation model. Generally, the program showed positive results and have been successful in engaging its participants to be more responsive when facing economic challenges in daily life.

Evaluation criteria for tumor efficacy in the times of immunotherapy

With the advent of the times of immunotherapy and the emergence of a variety of unconventional response patterns such as delayed response and pseudo-progressive disease, a variety of immune-related efficacy evaluation criteria such as immune-related response criteria, immune-related response evaluation criteria in solid tumor and immune response evaluation criteria in solid tumor have been proposed successively. The evaluation principles and judgment results of these criteria are distinctly different from the traditional response evaluation criteria. In particular, the newly proposed immune response evaluation criteria in solid tumor introduces two new concepts of unconfirmed progressive disease and confirmed progressive disease and provides a new response evaluation model for solid tumors, which is expected to provide solutions to some of the most urgent clinical problems under the times of cancer immunotherapy. Key words: Neoplasms; Immunotherapy; Response evaluation; Immune response evaluation criteria in solid tumors

Computational Design of an RF Controlled Theranostic Model for Evaluation of Tissue Biothermal Response

Human disease management strategies are gradually shifting from the traditional approach towards personalized medicine. Thermal therapy comprising of clinical hyperthermia and therapeutic hypothermia has been subject of recent research. However, both have suffered in clinical trials because thermal monitoring is not impressive and delivering the appropriate amount of heat to the appropriate part of the patient’s tissues is challenging. Hence, this study is aimed at addressing these challenges by technically merging the principles of magnetic resonance relaxation to the Bioheat transfer phenomenon. The analytical solutions to the Pennes Bioheat equation are connected to radiofrequency (RF) power absorption in tissue that is dependent on the magnetic resonance relaxation parameters. A carefully selected RF field is used to control the model for hyperthermia and therapeutic hypothermia. The solution obtained is then applied to hyperthermia treatment of tumours and therapeutic hypothermia of the brain. The thermal profiles obtained do not only show excellent contrasts between different tissues but real time monitoring of tissue thermal response is very impressive. By producing individualized virtual tumours that may predict disease progression, the thermal profiles based on the controlled parameters developed in this study can contribute to the ongoing dialogue regarding the design of appropriate response criteria, provide a means to perform virtual clinical trials to assess the likely benefit of novel neurotherapeutics, and move neuro-oncology toward individualized treatment plans optimized for maximum benefit.

MODEL DAN RANCANGAN EVALUASI PROGRAM BIMBINGAN DAN KONSELING

Evaluation is an attempt to obtain information on a regular, continuous, and comprehensive basis of the process and outcomes of the development of attitudes and behaviors, or the developmental tasks of the students through the program activities that have been implemented. Evaluation or assessment is an important part in the management or management of the implementation of guidance and counseling in accordance with the developments that occur both in the overall school program, social development and the challenges that occur in education so the program of guidance and counseling services should not be static or it to it. Similarly, from the development of the program itself, a program of guidance and counseling services needs to be developed and improved so that it can be designed and realized in accordance with the development needs of learners as one of the target service. Even if the evaluation service is not a direct service to the student, the evaluation will have an impact on the improvement of the services required by the student. So that in the end students can feel the impact of improvement or changes in accordance with the dynamics of aspects developed in a program. The model of evaluation arises because of continuous explanation efforts derived from human development and desire to try to apply the principles of evaluation on a more abstract scope including in the fields of education, behavior and art. In this paper we will present some models that can be used in the evaluation of guidance and counseling programs, ie goal attainment evaluation model, formative and summative evaluation model, responsive evaluation model and CIPP evaluation model (Context, Inputs, Process and Product). Some things to consider in designing evaluation of guidance and counseling programs are: title of activities, reasons of implementation, general goals and specific objectives, evaluation questions, methodologies used and procedures and steps of evaluation activities. Keywords: Evaluation, model, and design.

THE APPLICATIONOF ANDRAGOGICAL PRINCIPLES IN EDUCATION AND TRAINING

The aim of this research is to obtain an objective and comprehensive pictures about the results of applying the andragogical principles in the implementation of education and training. This research used evaluation research method with Stake’s Responsive Evaluation Model. The subject of this research is the training participants, training committees, facilitators, teacher trainers, and the training program supervisor. The data were collected through interview techniques, focus group discussion, observation, questionnaire, and document study.The results of this research showed that some of the component has met the criteria in the implementation of the program, but most of the component andother training aspects require further development. The fundamental weaknesses of the training implementations wereinadequate understanding of the conceptual of the facilitator’s to the adult learning principles. This hasimplicationsforthe whole training process and results achieved. However, the summary comes up to a conclusion that the implementation training at Educational Quality Assurance Institution of Maluku Province still need improvement, especially the aspect of application of adult learning principles.&#x0D; Keywords: AndragogicalPrinciples, Stake’s Responsive Evaluation Model.

Abstract IA07: Genetic determinants of tumor development, therapy response and resistance in mouse models of BRCA-deficient breast cancer

Abstract Heterozygous germline mutations in BRCA1 or BRCA2 strongly predispose to development of breast and ovarian cancer (as well as other cancer types) via loss of the remaining wildtype allele. BRCA1/2-deficient cancers are defective in DNA double-strand break (DSB) repair via homologous recombination (HR) and therefore hypersensitive to DNA-damaging agents, including platinum drugs and poly(ADP-ribose) polymerase (PARP) inhibitors. However, these treatments do not result in tumor eradication and eventually resistance develops. To maximize therapeutic efficacy of these drugs and achieve durable remissions, it is important to unravel the mechanisms by which these tumors acquire resistance to platinum drugs and PARP inhibitors, in order to develop combination therapies that prevent development of resistance or re-sensitize resistant tumors. To study therapy response and resistance in a realistic in vivo setting, we have established several genetically engineered mouse models (GEMMs) and patient-derived tumor xenograft (PDX) models for BRCA-deficient breast cancer. These mice develop mammary tumors that are characterized by genomic instability and hypersensitivity to DNA-damaging agents, including platinum drugs and PARP inhibitors. Using cross-species oncogenomics and reverse genetics, we have identified several cancer genes including p53, MYC and RB as critical drivers in BRCA1-associated breast cancer. In addition, we have used these mammary tumor models for preclinical evaluation of therapy response and elucidation of mechanisms of acquired drug resistance. Using functional genetic screens, reverse genetics and genomic analysis of therapy-resistant tumors, we found that therapy response and resistance of BRCA1-deficient mammary tumors to cisplatin and the clinical PARP inhibitor olaparib is affected by several factors, including drug efflux transporter activity, type of BRCA1 founder mutation and restoration of HR repair via loss of 53BP1 or REV7. Also BRCA1 re-activation via genetic or epigenetic mechanisms contributes to therapy resistance in PDX models of BRCA1-deficient breast cancer. Importantly, pharmacokinetic or HR-related mechanisms underlie olaparib-resistance in only a fraction of BRCA1/2-deficient mammary tumors, indicating the existence of additional, unknown mechanisms. Citation Format: Jos Jonkers. Genetic determinants of tumor development, therapy response and resistance in mouse models of BRCA-deficient breast cancer [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr IA07.

Using virtual learning environments in bricolage mode for orchestrating learning situations across physical and virtual spaces

Teachers usually implement their pedagogical ideas in Virtual Learning Environments (VLEs) in a continuous refinement approach also known as “bricolage”. Recently, different proposals have enabled the ubiquitous access to VLEs, thus extending the bricolage mode of operation to other learning spaces. However, such proposals tend to present several limitations for teachers to orchestrate learning situations conducted across different physical and virtual spaces. This paper presents an evaluation study that involved the across-spaces usage of Moodle in bricolage mode and learning buckets (configurable containers of learning artifacts) in multiple learning situations spanning five months in a course on Physical Education in the Natural Environment for pre-service teachers. The study followed a responsive evaluation model, in which we conducted an anticipatory data reduction using an existing orchestration framework (called “5 + 3 aspects”) for structuring data gathering and analysis. The results showed that learning buckets helped the teachers in the multiple aspects of orchestration, overcoming the limitations of alternative approaches in some specific orchestration aspects: helping the involved teachers to connect different physical and physical spaces, while supporting technologies and activities of their everyday practice, and transferring part of the orchestration load from teachers to students. The results also suggested lines of future improvement, including the awareness of outdoor activities.

Total Student Workload: Implications of the European Credit Transfer and Accumulation System for an Integrated, Problem-Based Medical Curriculum

PurposeHow much time students spent on unstructured self-study activities in problem-based learning is not clear. The study addressed this issue by (1) identifying the nature of students’ unstructured learning activities in a problem-based medical curriculum, (2) measuring the unstructured student workload per week and per semester, and (3) assigning European Credit Transfer and Accumulation System units to the medical problem-based modules based on calculating the total student workload. MethodNineteen undergraduate medical students in the pre-clerkship phase were enrolled in the study. Data about the nature of unstructured learning activities and the amount of time spent on them were collected through focus group interviews (n=19); and a log diary method (n=13) describing their unstructured educational activities over one week. A response evaluation model and a thematic description approach were employed for data collection and data analysis respectively. ResultsA broad variations of unstructured learning activities were identified. The unstructured student workload ranged from 33 to 41h/wk., while the total student workload was 63/58h/wk. for years 2 and 3 respectively. The total student workload in a 15-week semester was 945h in year 2 and 870h in year 3, which equates with about 34 and 31 European Credit Transfer and Accumulation System per semester for years 2 and 3, respectively. DiscussionMeasuring student total workload in a problem-based program is important for evading the associated overload, and improving the quality of teaching and learning. Calculating student workload in an integrated problem-based curriculum is a challenge. Total student workload is the foundation for determination of the European Credit Transfer and Accumulation System units. Measuring unstructured student workload (or “out-of-class” learning time) is an important component of total student workload. Assigning the European Credit Transfer and Accumulation System to problem-based programs improves its quality assurance, and has educational, curricular, and organizational impact. Therefore, student workload in such programs should be regularity monitored and evaluated.

A simplified Nonlinear Sway-Rocking model for evaluation of seismic response of structures on shallow foundations

This paper presents a simplified Nonlinear Sway-Rocking model as a preliminary design tool for seismic soil-structure interaction analysis. The proposed model is intended to capture the nonlinear load-displacement response of shallow foundations during strong earthquake events where foundation bearing capacity is fully mobilised. Emphasis is given to heavily-loaded structures resting on a saturated clay half-space. The variation of soil stiffness and strength with depth, referred to as soil non-homogeneity, is considered in the model. Although independent springs are utilised for each of the swaying and rocking motions, coupling between these motions is taken into account by expressing the load-displacement relations as functions of the factor of safety against vertical bearing capacity failure (FSv) and the moment-to-shear ratio (M/H). The simplified model has been calibrated and validated against results from a series of static push-over and dynamic analyses performed using a more rigorous finite-difference numerical model. Despite some limitations of the current implementation, the concept of this model gives engineers more degrees of freedom in defining their own model components, providing a good balance between simplicity, flexibility and accuracy.

An Evaluation of the SUMUR Program Implementation from the Naqib’s Perspective

The Sahsiah Unggul Murid (SUMUR) (Virtuous Student Character) program was recently introduced in all Sekolah Menengah Kebangsaan Agama (SMKA) (National Religious Secondary Schools) and Sekolah Agama Bantuan Kerajaan (SABK) (Government Aided Religious Schools) in Malaysia in the year 2010. This program has been implemented through usrah (mentoring group) with each group being headed by a naqib (student mentor). Nevertheless, the credibility of the student mentors themselves is a matter of discussion. There were student mentors who did not use an interesting style of delivery, lack closeness with usrah members, are too soft-spoken to be effectively heard and tardy for the program. The driving force for the implementation of this SUMUR program are the student mentors who are constantly close to students in the respective usrah groups. The objective of this study is to explore the role of the naqib in the implementation of this program, in addition to examining the naqib’s function in the building of the student character. The Stake Responsive Evaluation Model was used adopting a qualitative method through interviews which focused on five nuqaba’ (plural for naqib; male student mentor) and naqibat (plural for naqibah; female student mentor) at the SMKA Sheikh Haji Mohd Said in the State of Negeri Sembilan, Malaysia. Study findings argue that the naqib plays the role of an agent who invites to righteousness, prevents vice and strengthens the ties of brotherhood among usrah members; all of which in turn enhance the credibility of a naqib. Hence, training for the naqib needs to be enhanced from time to time in ensuring that the SUMUR program achieves the objectives set by the Islamic Education Division of the Malaysian Ministry of Education (MoE). In conclusion, the SUMUR program introduced has run smoothly in this school and has the advantages of enhancing student character, moving them closer to Allah (S.W.T.), training them for leadership, and bridging ukhuwwah (brotherhood or sisterhood). The naqib was found to play an important role in helping to implement the SUMUR program and building student character. It is suggested that there is a need for a more comprehensive study encompassing the views of school administrators and murabbi (guide teachers) on the running of this SUMUR program at the national level to ensure that program stays on the right track. DOI: 10.5901/mjss.2014.v5n29p19

Breast cancer tissue slices as a model for evaluation of response to rapamycin

Rapamycin is a selective inhibitor of the mammalian target of rapamycin (mTOR), a regulator kinase that integrates growth factors signaling via the phosphoinositide-3-kinase pathway and that has emerged as a novel therapeutic modality in breast cancer (BC). We propose a pre-clinical "ex-vivo" personalized organotypic culture of BC that preserves the microenvironment to evaluate rapamycin-mediated gene expression changes. Freshly excised ductal invasive BC slices, 400 μm thick (n=30), were cultured in the presence or absence (control) of rapamycin (20 nM) for 24 h. Some slices were formalin-fixed for immunohistochemical determinations and some were processed for microarray analysis. Control slices in culture retained their tissue morphology and tissue viability (detected by BrdU uptake). The percentage of proliferating cells (assessed by Ki67) did not change up to 24 h of treatment. Immunohistochemical evaluation of p-AKT, p-mTOR, p-4EBP1 and p-S6K1 indicated that AKT/mTOR pathway activation was maintained during cultivation. For microarray analysis, slices were divided into two groups, according to the presence/absence of epidermal growth factor receptor-type 2 and analyzed separately. Limited overlap was seen among differentially expressed genes after treatment (P<0.01) in both groups suggesting different responses to rapamycin between these BC subtypes. Ontology analysis indicated that genes involved in biosynthetic processes were commonly reduced by rapamycin. Our network analysis suggested that concerted expression of these genes might distinguish controls from treated slices. Thus, breast carcinoma slices constitute a suitable physiological tool to evaluate the short-term effects of rapamycin on the gene profile of individual BC samples.

Thermomechanical model for evaluation of the superelastic response of NiTi shape memory alloys under dynamic conditions

The development of a 1D thermomechanical model for simulating the response of uniaxial superelastic NiTi elements is described. The formulation of the model includes consideration of the dependence of the critical stresses for forward and reverse transformation on the temperature, the occurrence of strain rate effects due to self-heating/cooling associated with the latent heat of the stress induced martensitic transformation, the localized character of the stress induced transformation in superelastic NiTi wires and ribbons, the possibility of nucleation events during both the forward and reverse transformations and the occurrence of non-recoverable residual strains. Numerical simulations allowed rationalization of different features commonly observed in experiments and their dependence on strain rate and environment conditions. Comparisons of numerical results with experimental cycles obtained in the present work and also with data published in the literature indicate the potentiality of the developed model as a design tool for simulating the response of superelastic materials subjected to realistic service conditions.

A novel implantation model for evaluation of bone healing response to dental implants: the goat iliac crest

Despite the availability of numerous animal models for testing the biological performance of dental and orthopedic implants, the selection of a suitable model is complex. This paper presents a new model for objective and standardized evaluation of bone responses to implants using the iliac crest in goats. The feasibility of the iliac crest model regarding anatomy and implant positioning was determined using two cadaveric specimens and the bone structure was evaluated and compared with that of the goat femoral condyle. Additionally, the validity of the model was tested by performing an in vivo study. By means of a rather simple, safe, fast and reproducible surgical procedure, the iliac crest in goats could be approached and allowed the implantation of maximally five dental implants per iliac crest. Because of the bilateral implantation possibility, statistical comparisons between groups on either side of the goat could be performed, resulting in a high statistical power, and hence a reduction in the number of animals required to obtain significant data. In terms of surgical approach, anatomy and implant positioning, the iliac crest is the preferred model over the femoral condyle model. The iliac crest implantation model is suitable for evaluation of the osteogenic response to bone implant materials and represents a justified and deliberate alternative to the already existing animal models.

A Direct Comparison of High Dose Cytarabine to Combination of Gemtuzumab and High Dose Cytarabine for Acute Myeloid Leukemia Patients in First Relapse Confirmed the Benefit of Gemtuzumab Based Regimens.

Abstract 2051Poster Board II-28Acute meyloid leukemia (AML) in first relapse is associated with a poor outcome when treated with standard dose cytarabine regimens and intermediate to high dose cytarabine (IHDAraC) is the current standard of care. During the last years, Gemtuzumab Ozogamycin (GO) has demonstrated a relevant clinical activity in relapsed and refractory AML. This antibody directed against CD33 is conjugated to calicheamycin that triggers apoptosis when hydrolyzed in the leukemic blasts. Combination regimen of GO are currently extensively studied in both frontline and advanced phase disease. Nevertheless, analysis of the litterature showed that only few data are available regarding a direct comparison of IHDAraC and IHDAraC+GO regimen. To this respect, we conduced a retrospective analysis of response (CR and CRi) and survival for patients with first relapse AML treated in our centre with either IHDAraC or IHDAraC+GO regimen. A total of 84 patients were included in the analysis: 28 were induced in the IHDAraC+GO group (mean GO dose: 6mg/m2, range:[3-9], including 82% of combination with anthracyclines or etoposide) and 56 in the IHDAraC group (including 57% of combination with other agents, mostly etoposide and anthracyclines). Patients characteristics were comparable between the IHDAraC+GO group and the control group in terms of median age (51y vs 49y), Performance Status at relapse (1 vs 1), median time to relapse (221 days vs 280 days), cytogenetic risk group clustering and previous allogeneic transplantation in first CR (21% vs 16%). Median Follow-up was 24 months. Univariate analysis showed that IHDAraC+GO induction, as compared with IHDAraC, was associated with a better response rate (68% vs 48%, p=0.08), a lower relapse rate (31% vs 66%, p=0.02), a better Overall Survival (median 35 months vs 19 months, p=0.02) and a better Event Free Survival (median Not Reached vs 10 months, p=0.02). Of note, the better response rate in the IHDAraC+GO group allowed to bring more patients to allogeneic transplantation in second CR (33% vs 16% respectively, p=0.08).Multivariate analysis using logistic regression method for response evaluation and Cox model for survival showed that treatment in the IHDAraC+GO group was an independent prognosis factor with a favorable impact on both response (HR:2.8, 95%CI:[1.1-7.7], p=0.048) and Overall Survival (HR:1.9, 95%CI:[1.1-3.4], p=0.047). It is already known that combination of IHDAraC and GO could give good results for advanced phase AML patients but, to our knowledge, this report is the first that directly compared the results of IHDAraC+GO with the current standard of care regimen on an homogeneous sample of patients in first relapse. This report also underline the importance of a prospective comparison in order to define the best combination therapy. Disclosures:No relevant conflicts of interest to declare.

Human-in-mouse modeling of primary head and neck squamous cell carcinoma

To develop a reliable modeling system for head and neck squamous cell carcinoma (HNSCC). Laboratory-based translational study. HNSCC tissue was obtained from patients at biopsy/resection, cultured, and implanted into mice. In vivo, tumor growth, and survival was monitored by bioluminescence imaging. Histology and immunohistochemistry (IHC) were used to confirm HNSCC and human origin. Short-term culture techniques were optimized allowing survival of primary HNSCC cells more than 7 days in 76% of tumors. The size of the tumor biopsy collected did not correlate with the success of short-term culture or xenograft establishment. Xenograft modeling was attempted in primary HNSCCs from 12 patients with a success rate of 92%. Immunostaining confirmed human origin of epithelial tumor cells within the modeled tumor. Bioluminescence and Ki67 IHC suggested tumor proliferation within the model. Luciferase expression was maintained for as long as 100 days in modeled tumors. The techniques developed for short-term primary tumor culture followed by xenograft modeling provide a low-cost and tractable model for evaluation of HNSCC response to standard and novel therapies. The high success rate of human-in-mouse tumor formation from primary HNSCC suggests that selection pressures for tumor growth in this model may be less than those observed for establishment of cell lines. Bioluminescent imaging provides a useful tool for evaluating tumor growth and could be expanded to measure response of the modeled tumor to therapy. This model could be adapted for xenograft modeled growth of other primary tumor types.