Single Grade Research Articles

An enhanced co-simulation technique for resource modelling using grade domaining: a case study from an iron ore deposit

ABSTRACT For resource estimation, domains are interpreted in a deposit to define homogenous areas for grade estimation. The conventional approach is to interpret the domains and then to separately model the distribution of the grade (i.e., partial grades) within each domain. The problem is that independent modeling of partial grades ignores the cross-dependency that exists between the partial grades within the defined domains. In this study, an alternative is proposed to first model the grade domains using a stochastic approach and then to model the partial grades within each domain using a co-simulation algorithm that incorporates their cross-correlation structures. The proposed enhanced co-simulation methodology has been applied at an iron deposit and a single grade threshold. This case study shows that the enhanced co-simulation methodology is capable of reproducing the global statistics and spatial continuity characteristics of the partial grades and results in improved domaining, grade estimation and definition of ore.

Hemivertebrectomy of L5 in Grade 2 Chondrosarcoma: Is a Single Posterior Approach with No Nerve Root Sacrifice Possible? A Case Report

En-bloc resection of spine tumors is difficult to achieve compared to extremities tumors for anatomical reason. Several surgical techniques have been described, such as combined multiple surgical approaches or an enlarged single posterior approach. These demanding strategies correlate with high rate of intraoperative/postoperative complications. The current case is about a patient treated with a single posterior-lateral surgical approach to perform hemivertebrectomy of L5 for a single grade 2 chondrosarcoma metastasis (WBB 2-5/b-c). Usually, L5 hemivertebrectomy requires a combined surgical approach to preserve L5 root. The final solution was to perform a T-shape skin incision: a longitudinal branch centered on the vertebral spine and a transverse branch on the iliac crest. This approach allowed osteotomy of the ipsilateral iliac crest, achieving sufficient view to preserve L5 root and vessels anteriorly; the same osteotomy was used to create a bone autograft to reconstruct the residual part of L5. Finally, cryotherapy was used in order to increase the adequacy of surgical margins. A L3-S1 arthrodesis is assembled to achieve stability of the system. Surgical time was 5 hours, no nerve roots have been sacrificed nor any other intraoperative complications occurred. This surgical technique had never been described before in literature.

Application Research on Objective Evaluation of Vehicle Interior Odor Based On Weber-Fechner Law

In this paper, four typical compounds of odorants were selected as the research objects. The mathematical model hypothesis is established which based on the Weber-Fechner law, and then the relationship between the concentration of odor substances and the odor grade is verified to judge whether this law is applicable to the objective evaluation of vehicle interior odor. The results show that: the concentration of single odor substance and odor grade, the concentration of two kinds of odor substances and odor grade are in accordance with this law. It is proved that the relationship between odor substance concentration and odor grade conforms to the law to a certain extent, which provides an important theoretical basis for objective evaluation of vehicle interior odor and control vehicle environment to create an environmental and healthy vehicle.

Effect of the double grading on the internal electric field and on the carrier collection in CIGS solar cells

In this article, we look, from the carrier perspective, at the effect of the double grading in a CIGS absorber, in order to understand its benefit compared to a single grading. We focus on the double grading effects on the conduction band edge, generation rate and carrier collection. We first show that, when the minimum bandgap position (notch position) is outside of the absorber depletion region, a local maximum of the conduction band edge appears at the back of the depletion region, creating a hump, which hinders the collection of electrons. Interpreting the effect of the grading as an effective electric field, we show that the hump is caused by the competition between the absorber internal electric field and the grading created effective electric field. From this, we deduce that the notch should be positioned in the depletion region. As expected, the generation rate increases significantly at the notch position. However, studying carrier collection and the recombination rate, we show that, even if in the ideal case we should observe a total collection of carriers generated in the depletion region, the recombination rate in the SCR increases significantly when the notch is in it. We propose that this is caused by the increased carrier generation close to recombination centres. The ideal notch position is, therefore, a compromise between being close enough to the front to have a maximal carrier collection and avoiding the creation of a hump, while minimizing the carrier recombination.

Optimization of parameters and fabrication of micro channel heat sinks using micro scanning EDM and grey relational analysis

Micro-Channel Heat Sinkisan effective and efficient device that can circumvent excess heat from the batteries of an electrical car. Coolants with less resistances are used as carriers of heat from the batteries through the channels. In this research, a novel approach of fabricating micro channels on copper using Micro-Scanning Electrical Discharge Machining (MSEDM) through a multi-functional transistor and capacitance based micromachine is done. The total thickness of the heat sinkis1.2 mm with0.5 mm of channel depth and channel width. A full factorial design of experiments with the input parameters of Voltage(V), Capacitance(pf)and(μs) are considered to get 32 experiments in total. Grey Relational Analysis (GRA) is used to optimize the response parameters MRR, TWR and Channel dilation. The multiple responses are converted into one single Grey Relational Grade and the optimum parameters are selected. Results show that the capacitance is the most influential parameter followed by voltage and then Ton. Also, a parameter combination of Ton = 90 µs, Voltage = 130 V and Capacitance = 100000pf reduces the Channel dilation, MRR andTWR.

Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library designed for eliciting patient-reported adverse events in oncology. For each adverse event, up to three individual items are scored for frequency, severity, and interference with daily activities. To align the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events with other standardized tools for adverse event assessment including the Common Terminology Criteria for Adverse Events, an algorithm for mapping individual items for any given adverse event to a single composite numerical grade was developed and tested. A five-step process was used: (1) All 179 possible Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events score combinations were presented to 20 clinical investigators to subjectively map combinations to single numerical grades ranging from 0 to 3. (2) Combinations with <75% agreement were presented to investigator committees at a National Clinical Trials Network cooperative group meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability, and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating adverse events between study arms was measured in two Phase III clinical trials (NCT02066181 and NCT01522443). In Step 1, 12/179 score combinations had <75% initial agreement. In Step 2, majority consensus was reached for all combinations. In Step 3, five grades were adjusted to assure directional consistency. In Steps 4 and 5, composite grades performed well and comparably to individual item scores on validity, reliability, sensitivity, and between-arm delineation. A composite grading algorithm has been developed and yields single numerical grades for adverse events assessed via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, and can be useful in analyses and reporting.

Stereotactic Body Radiation Therapy for Mediastinal and Hilar Lymph Node Metastases

Stereotactic body radiation therapy (SBRT) to metastatic mediastinal and hilar lymphadenopathy (MHL) is challenging owing to the proximity of centrally located organs-at-risk. As limited data exist on the safety and efficacy of SBRT for MHL, a retrospective review of clinical outcomes was conducted from a large academic center. Eligible patients received SBRT to MHL between 2014 to 2019 for the following indications: oligometastases, oligoprogression, or local control of a dominant area of progression. The primary endpoint was grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). The cumulative incidence function evaluated local failure (LF) and starting or changing systemic therapy (SCST). Kaplan-Meier methodology estimated progression-free survival (PFS) and overall survival (OS). Fifty-two patients (84 metastases) were included. Median follow-up was 20 months. Primary cancer sites included kidney (53.8%), lung (13.4%), breast (7.7%), and other (25.1%). Indications for SBRT were oligoprogression (n = 35; 67.3%), oligometastases (n = 10; 19.2%), or local failure of a dominant area of progression (n = 7; 13.5%). The majority (n = 31; 59.6%) received SBRT to a single lymph node metastasis. Median SBRT dose was 35 Gy (range, 30-50 Gy) with a median biologically effective dose of 59.5 Gy (range, 48-100 Gy). All treatments were in 5 fractions. Seven grade ≥3 toxicities were experienced by 6 patients (11.5%) and were mostly transient (5/7; 71%). There was a single (1.9%) grade 5 toxicity (radiation pneumonitis). The cumulative incidence of LF was 9.0% at 2 years. The cumulative incidence of SCST was 33.2% and 57.1% at 1 and 2 years, respectively. Median PFS was 4.0 months (95% confidence interval, 2.8-7.3) and median OS was 31.7 months (95% confidence interval, 23.8-87.5). In one of the largest single institutional series of SBRT for MHL, moderate rates of grade ≥3 toxicity were observed, although the majority were transient. This treatment resulted in low LF rates and potentially delayed SCST for many patients.

Sunitinib in Patients with Metastatic Colorectal Cancer (mCRC) with FLT-3 Amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

TAPUR is a pragmatic, phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Sunitinib is an oral multikinase inhibitor of FMS-like tyrosine kinase-3 (FLT-3), among other targets. Results from a cohort of patients with metastatic colorectal cancer (mCRC) with FLT-3 amplification treated with sunitinib are reported. This study aimed to investigate whether patients with mCRC with FLT-3 amplification would be responsive to sunitinib, an oral multikinase inhibitor. Eligible patients received a standard sunitinib dose of 50mg orally for 4weeks followed by 2weeks off. Simon's two-stage design was used with the primary study endpoint of objective response (OR) or stable disease (SD) at 16weeks based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints were progression-free survival, overall survival, and safety. Ten patients were enrolled from November 2016 to April 2018. All patients had mCRC with FLT-3 amplification. No ORs were observed. Although two patients had SD at 16weeks, one died because of disease progression shortly thereafter and the cohort was closed. A single grade 3 adverse event of diarrhea was reported as possibly related to sunitinib. Monotherapy with sunitinib does not have clinical activity in patients with mCRC with FLT-3 amplification and should not be prescribed for off-label use. Other treatments should be considered for these patients, including treatments offered in clinical trials. NCT02693535 (26 February 2016).

Svenska lärares syn på avvikelser mellan resultat på nationella prov och ämnesbetyg

Since 2018, Swedish teachers are expected to pay particular attention to pupils’ results on national tests when grading. There are, however, still large discrepancies between national test results and teachers’ grades, which differ between schools and subjects. The purpose of this study is to investigate possible reasons behind these differences, from a teacher perspective. The study is based on semi-structured interviews with teachers who teach grade 9, either in physics (n=9) or English (n=12). The interviews have been transcribed and analyzed with thematic content analysis. The most important reason for differences is that the test results are considered misleading by the teachers. Although most reasons for considering the test results as misleading relate to test design, some of the reasons relate to the pupils. The only reason for differences that does not relate to test results being considered misleading, is that some pupils receive instruction at the end of the semester based on their shortcomings identified in the test. Furthermore, since the teachers tend to compare test results and own grades in a 1:1 ratio, they may discard the entire test if it is considered misleading. The fact that test results are presented as a single score or grade, therefore, seems to contribute to teachers not paying particular attention to test results when grading.

Development and validation of a novel pseudogene pair-based prognostic signature for prediction of overall survival in patients with hepatocellular carcinoma

BackgroundThere is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and robust pseudogene pairs-based signature for the prognosis of hepatocellular carcinoma (HCC).MethodsRNA-sequencing data from 374 HCC patients with clinical follow-up information were obtained from the Cancer Genome Atlas (TCGA) database and used in this study. Survival-related pseudogene pairs were identified, and a signature model was constructed by Cox regression analysis (univariate and least absolute shrinkage and selection operator). All individuals were classified into high- and low-risk groups based on the optimal cutoff. Subgroups analysis of the novel signature was conducted and validated in an independent cohort. Pearson correlation analyses were carried out between the included pseudogenes and the protein-coding genes based on their expression levels. Enrichment analysis was performed to predict the possible role of the pseudogenes identified in the signature.ResultsA 19-pseudogene pair signature, which included 21 pseudogenes, was established. Patients in high-risk group demonstrated an increased the risk of adverse prognosis in the TCGA cohort and the external cohort (all P < 0.001). The novel pseudogene signature was independent of other conventional clinical variables used for survival prediction in HCC patients in the two cohorts revealed by the multivariate Cox regression analysis (all P < 0.001). Subgroup analysis further demonstrated the diagnostic value of the signature across different stages, grades, sexes, and age groups. The C-index of the prognostic signature was 0.761, which was not only higher than that of several previous risk models but was also much higher than that of a single age, sex, grade, and stage risk model. Furthermore, functional analysis revealed that the potential biological mechanisms mediated by these pseudogenes are primarily involved in cytokine receptor activity, T cell receptor signaling, chemokine signaling, NF-κB signaling, PD-L1 expression, and the PD-1 checkpoint pathway in cancer.ConclusionThe novel proposed and validated pseudogene pair-based signature may serve as a valuable independent prognostic predictor for predicting survival of patients with HCC.

The Valuable Reference of Live Birth Rate in the Single Vitrified-Warmed BB/BC/CB Blastocyst Transfer: The Cleavage-Stage Embryo Quality and Embryo Development Speed

BackgroundIt is unclear whether we should focus attention on cleavage-stage embryo quality and embryo development speed when transferring single particular grade vitrified-warmed blastocysts, especially poor-quality blastocysts (grade “C”).MethodThis retrospective study considered 3386 single vitrified-warmed blastocyst transfer cycles from January 2010 to December 2017. They were divided into group 1 (AA/AB/BA, n = 374), group 2 (BB, n = 1789), group 3 (BC, n = 901), and group 4 (CB, n = 322). The effects of cleavage-stage embryo quality and embryo development speed were measured in terms of clinical pregnancy and live birth rates in each group.ResultsPregnancy outcomes showed a worsening trend from groups 1 to 4; the proportion of embryos with better cleavage-stage quality and faster development speed decreased. In group 1, only the blastocyst expansion degree 3 was a negative factor in the clinical pregnancy rate (odds ratio (OR) [95% confidence interval (CI)]: 0.233 [0.091–0.595]) and live birth rate (0.280 [0.093–0.884]). In the other groups (BB, BC, and CB), blastocysts frozen on day 5 had significantly better clinical pregnancy outcomes than those frozen on day 6: 1.373 [1.095–1.722] for group 2, 1.523 [1.055–2.197] for group 3, and 3.627 [1.715–7.671] for group 4. The live birth rate was 1.342 [1.060–1.700] for group 2, 1.544 [1.058–2.253] in group 3, and 3.202 [1.509–6.795] in group 4, all Ps < 0.05). The degree of blastocoel expansion three for clinical pregnancy rate in group 2 (0.350 [0.135–0.906], P < 0.05) and day 3 blastomere number (>7) for live birth rate in group 4 (2.455 [1.190–5.063], P < 0.05) were two important factors.ConclusionWe should consider choosing BB/BC/CB grade blastocysts frozen on day 5, CB grade blastocysts with day 3 blastomere numbers (>7), and AA/AB/BA grade blastocysts with degrees of expansion (≥4) to obtain better pregnancy outcomes.

Quantitative NIR spectroscopy determination of coco-peat substrate moisture content: Effect of particle size and non-uniformity

The particle size and non-uniformity of solid particle samples directly affected the acquisition of samples spectral data. In this study, different particle size samples and mixed samples with two different particle size grade samples were applied to investigate the impact of particle size and non-uniformity on near-infrared (NIR) spectroscopy detection of moisture content in coco-peat substrate. Simultaneously, the pretreatment effect and capability of MSC and SNV on spectral scattering were studied. The results showed that the prediction accuracy of the spectral detection model for moisture content in coco-peat substrate was higher with smaller particle size or smaller non-uniformity; MSC and SNV had better effects on improving the accuracy of prediction models with small particle size samples or small non-uniformity samples; the optimal moisture content spectral prediction models for single particle size grade samples and mixed samples of two particle size grades could be respectively established when SNV was adopted to pretreat the samples spectral data of A and A-B. And the corresponding correlation coefficients of the two optimal models were 0.9964 and 0.9959 for calibration set, 0.9959 and 0.9957 for prediction set, respectively; the root mean square errors were 1.2299% and 1.0090% for calibration set, 1.2820% and 1.0723% for prediction set, respectively; the ratios of prediction to deviation were 10.83 and 10.51, respectively. The prediction model with the minimal spectral scattering influence could be built by combining physical pretreatment with spectral pretreatment. This study would provide a reference for reducing the scattering effect of solid particle sample spectral detection.

Chemosensory aerosol assessment of key attributes for tobacco products

AbstractHuman sensory evaluation plays an important role in assessing quality and supports commercial product development in many industries. However, sensory evaluation of tobacco products often requires highly trained specialists, is thus expensive, time‐consuming with low throughput capacity. To overcome such limitations, analytical platforms based on chemical fingerprints were proposed and evaluated in this work based on two different tobacco matrices. Using cigarette smoke as an example, the method was capable of predicting sensory attributes through chemical fingerprinting key tobacco and cigarette mainstream aerosol compositions. To achieve this, tobacco samples (comprising flue‐cured Virginia and air‐cured Burley types) and cigarette mainstream smoke samples were evaluated using high‐resolution mass spectrometry. The chemical fingerprint of each sample matrix was related to its respective reference sensory attributes, validated by highly trained panellists, to create predictive models based on partial least squares algorithm. These methodologies were further validated through a blind test with suitable prediction of all sensory attributes for single grade tobacco leaf and commercial blended cigarette smoke. The proposed methodology demonstrated satisfactory accuracy, repeatability and robustness, with prediction errors less than 20% for single grade tobaccos, and less than 11% for commercial products. When compared with human sensory evaluation, it significantly improved analytical capacity (over 100 samples per day) at comparable or improved accuracy. This method could be applied to evaluate other novel tobacco products such as heated tobacco products.

The Immediate Effects of Ankle Joint Mobilization on Ankle Musculotendinous Stiffness in Individuals With Chronic Ankle Instability

Ankle joint mobilization has been shown to be effective at improving outcomes in those with chronic ankle instability (CAI), but the neuromuscular mechanisms are still unknown. We aimed to determine the immediate effect of a single Grade III anterior-to-posterior ankle joint mobilization bout on ankle musculotendinous stiffness (MTS) in those with CAI. Seventeen CAI participants had plantar flexor and fibularis MTS assessed before and after a 5-min joint mobilization treatment. MTS outcomes were estimated using the damped oscillation method. Fibularis (0.25 ± 0.41 N/m/kg, p = .028) but not plantar flexor MTS (−2.18 ± 14.35 N/m/kg, p = .539) changed following mobilization and exceeded the calculated minimal detectable change score (0.12 N/m/kg). Increased fibularis MTS may represent a neuromuscular mechanism by which ankle joint mobilizations improve postural control in those with CAI.

A novel ablative radiofrequency microplasma nonsurgical blepharoplasty for dermatochalasis

Dermatochalasis (DC) is part of the aging process of the eyelids, characterized by lax, redundant, and overhanging excess eyelid skin. Mostly, it is treated by surgical blepharoplasty. Lately alternative nonsurgical blepharoplasty technologies have been introduced. In this study, we evaluated the efficacy and safety of a novel noninvasive RF microplasma technology for upper eyelid DC. A prospective single center study included 17 patients with moderate to severe upper eyelid DC. Subjects were treated by controlled micro-plasma sparks via a single tip leading to superficial ablation and coagulation at the treatment area. One to three treatment sessions at 2 months interval were performed. Three blinded observers evaluated the photographs taken at baseline and at 6 to 8 months follow-up visit following the final treatment session. Treatment efficacy was assessed using a 4-point grading scale. Seven out of 17 patients (41%) treated for DC by the single microplasma spark exhibited a 2 grade improvement on a 4 point DC scale. 10 out of 17 (59%) patients showed a single grade improvement on a 4 point DC scale. No adverse side effects were observed. Noninvasive ablative microplasma may offer safe and effective therapy for upper eyelid DC.

DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation.

The aim of the present work was the development of a novel glycosaminoglycan (GAG)-based injectable formulation intended for intra-articular administration that should best mimic the healthy synovial fluid. Hyaluronic acid (HA) was chosen among GAG polymers, since it is the most abundant component of the synovial fluid. A DoE (Design of Experiment) approach was used for the development of a formulation containing two HA (very high (VHMW) and low (LMW) molecular weight) grades. The rationale for this choice is that so far, no commercial product based on a single HA grade or even on binary HA mixture possesses optimal viscoelastic properties in comparison with healthy synovial fluid. A full factorial design was chosen to investigate the influence of concentration and relative fraction of the two polymer grades (retained as factors of the model) on formulation functional (viscosity and viscoelastic) properties, which are considered response variables. Thanks to the DoE approach, the composition of the optimized HA formulation was found. The addition to such formulation of an injectable grade fat-free soy phospholipid, which was rich in phosphatidylcholine (PC), resulted in improved lubrication properties. The final HA + PC formulation, packaged in pre-filled sterile syringes, was stable in long-term and accelerated ICH (International Council for Harmonisation) storage conditions. The overall results pointed out the formulation suitability for further steps of pharmaceutical developments, namely for the passage to pilot scale.

Efficacy of SCRI-CAR19x22 T cell product in B-ALL and persistence of anti-CD22 activity.

3035 Background: Loss of CD19 expression is a major cause of limited durable B-ALL remission following CD19 CAR T cells, which might be overcome by utilization of dual CD19xCD22 CAR T cell targeting. Methods: A Phase I trial (NCT03330691) of SCRI-CAR19x22 was developed using dual transduction of lentiviral vectors encoding for either a CD19- or CD22-specific CAR T cell construct, both with 4-1BB co-stimulation. Manufacturing was performed in a closed G-Rex system with IL-7, IL-15 and IL-21. After lymphodepletion, CAR T cells were infused at 1 or 3 X 106 CAR T cells/kg dose levels. Leukemic response and CAR T cell persistence were evaluated by flow cytometry. Results: Products were successfully manufactured in all 28 enrolled subjects with 7.92 average days in culture (range of 7-11 days) and consisted of an average CD8:CD4 ratio of 3.09 (range 0.19 to 8.9). The cellular product CAR composition was 29% CD19, 31% CD22 and 39% CD19 and CD22 targeting. 13 subjects had prior exposure to CD19 or CD22 targeting therapies with diverse expression of CD19 and CD22 on the leukemic blasts. No dose limiting toxicities occurred in the 27 infused subjects. The recommended phase 2 dose is 3 x 106 CAR+ cells/kg. CRS was present in 80% of subjects, with 85% of CRS being grade 2 or less, and a peak grade of 3 (n = 3). Mild neurotoxicity occurred in 38%, with a single grade 3 event. 84.6% obtained a CR, of which 95% were MRD negative. Of the 4 subjects who did not achieved a CR, 2 had a pre-existing CD19 negative population and one had previously received CAR T cells and rejected SCRI-CAR19x22. There have been 4 relapses with varying CD19 and CD22 expression as follows: 1 CD19-CD22-, 1 CD19+CD22+, and 2 CD19-CD22+. The in vivo engraftment of CAR T cells peaked most frequently between day +7 and +14 and was predominated by the CD19 CAR+ T cells. Conclusions: We demonstrate manufacturing feasibility and safety of SCRI-CAR19x22. While initial efficacy is demonstrated, CD22 activity is poor due to limited expansion of the CD22 CAR-containing components and subjects with pre-existing CD19 negative leukemia fared poorly. Development of a revised CD22 CAR that exhibits a reduction tonic signaling is underway, with plans to explore the new construct in the context of a dual-targeting CD19xCD22 CAR T cell product. Clinical trial information: NCT03330691 .

Composite grading algorithm for National Cancer Institute’s PRO-CTCAE.

7018 Background: Standard reporting of symptomatic adverse events (AEs) in oncology relies on clinicians to rate patient (pt) experience using CTCAE; each symptom is represented by a single graded item. To capture direct pt experience, NCI developed PRO-CTCAE to supplement CTCAE. In PRO-CTCAE, the pt answers up to 3 questions per AE about a symptom’s frequency, severity and interference with daily activities. To align PRO-CTCAE with CTCAE, we developed an algorithm for mapping sets of questions for an AE to a single composite numerical grade. Methods: We used a 5-step process. (1) All 187 possible PRO-CTCAE score permutations were presented to clinical investigators to subjectively map permutations to single numerical grades (range 0-3). (2) Permutations with &lt; 75% agreement were presented to investigator committees at a National Clinical Trials Network meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating AEs between study arms was measured in 2 phase III clinical trials (Alliance for Clinical Trials in Oncology A091105 and Exelixis COMET-2). Results: (1) 12/187 score permutations had &lt; 75% initial agreement. (2) Majority consensus was reached for all permutations. (3) 5 mappings were adjusted to assure directional consistency. (4) Composite grades for 46/59 (78%) AEs were higher in pts with ECOG performance status 2-4 vs 0-1 (median effect size 0.23 [range -0.49-0.73]; 32/59 effect size ≥0.2; 25/59 p&lt; 0.05), similar to when conducting analysis on individual unmapped items. The test-retest reliability for 24 selected composite grades ranged from 0.57-0.96 (median intraclass correlation coefficient [ICC] 0.77) with 18/24 (75%) grades having ICC ≥0.7. Median (range) standardized response means in pts reporting worsening, no change, and improvement were 0.20 (0.03-0.34), -0.06 (-0.20-0.03) and -0.12 (-0.32-0.06). (5) Pattern, directionality and statistical significance of between-arm differences in both trials were preserved with composite grades as compared to individual unmapped items. Conclusions: A composite grading algorithm for PRO-CTCAE was rigorously developed and validated. PRO-CTCAE composite grades may be useful in analyses to provide a single metric for each pt-reported AE for trial and real-world reporting. Support: UG1CA189823; U01CA233046; HHSN261200800043C; Bayer (A091105); https://acknowledgments.alliancefound.org .

Early childhood professional culture: Social networks and beliefs among pre-kindergarten educators

As efforts are made in the United States for public school districts to implement pre-kindergarten programs and centers, there is a growing need to attend to the aspects of the local context that may influence the ways that teachers and staff make sense of their work. Yet, the professional cultures in which early childhood teachers and other educators make sense of their practice are multi-faceted and not well understood. This study explores the network structures and beliefs among educators in three pre-kindergarten centers. In particular, the mentorship relationships among lead teachers, assistants, instructional coaches, and administrators were explored along with individuals’ beliefs about themselves and others. Findings indicate that early childhood mentoring networks aligned with formal role hierarchies, and were similar to networks seen in elementary school research. Trust among lead and assistant teachers and autonomy were particularly important in the pre-kindergarten settings where two individuals work together as part of a classroom teaching team, and the school serves a single grade level. Suggestions for future research expanding the work on professional culture in early childhood settings are addressed.

PD12-07 A PHASE III STUDY TO EVALUATE THE SAFETY AND EFFICACY OF INTRAVESICAL NADOFARAGENE FIRADENOVEC FOR PATIENTS WITH HIGH-GRADE, BCG UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER

INTRODUCTION AND OBJECTIVE: A subset of patients (pts) with high-grade non-muscle invasive bladder cancer (NMIBC) who are treated with BCG will have BCG unresponsive disease, and are at considerable risk for tumor recurrence and progression. The development of effective intravesical therapies represents an important unmet need in this population. Nadofaragene firadenovec is a novel intravesical gene-mediated therapy that delivers the human IFNα2b gene resulting in sustained IFNα2b expression, and provided durable responses in a previous Phase 2 trial. Herein, we report results from the papillary disease (PD) cohort of the Phase 3 trial. METHODS: This multicenter, open-label Phase 3 study investigated nadofaragene for high-grade NMIBC (carcinoma in situ [CIS ± Ta/T1], or PD [Ta/T1 alone]) unresponsive to BCG. Nadofaragene (3X1011 vp/mL [75 mL]) was administered intravesically once every 3 months for up 4 doses in the initial 12 months. Pts with no evidence of high-grade disease at month 12 were offered continued treatment at the investigator’s discretion. The primary endpoint was complete response (CR) rate at any time in the CIS cohort (results presented in a prior abstract). Secondary end points included rate and durability of high-grade-recurrence-free (HGRF) survival as well as safety in PD pts, reported herein. RESULTS: A total of 157 pts were enrolled, of whom 50 were in the PD cohort (safety population n=50; efficacy population n=48). At study entry, all pts were BCG-unresponsive. Of the 48 pts in the efficacy population, 35 (72.9%), 30 (62.5%), 28 (58.3%), and 21 (43.8%) achieved HGRF survival at months 3, 6, 9, and 12, respectively. Within this PD cohort, the most common treatment-emergent adverse events (TEAEs) were transient in nature; specifically, instillation site discharge 30%; bladder spasm 18%; micturition urgency 18%; urinary tract infection 18%. The most common drug-related TEAEs were instillation site discharge 26%; bladder spasm 14%; micturition urgency 14%; dysuria 14%. Grade 3 TEAEs were reported in 9 pts (3 study drug-related), with a single Grade 4 (not related to study drug). No pt had an adverse event leading to death. CONCLUSIONS: Nadofaregene firadenovec was well tolerated and achieved an encouraging, durable HGRF survival in high-grade BCG-unresponsive NMIBC pts with PD. This demonstrates a clinically meaningful benefit in a pt population for whom to date non-surgical treatment options have remained limited. Clinical trial information: NCT02773849. Source of Funding: FKD