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Forecasted population growth in rural/urban interface areas will expose more residents and homes to an increased bushfire risk. As a result, fighting bushfires at the rural/urban interface is likely to become more frequent, but currently little is known about the air toxins emitted and exposure concentrations inhaled by firefighters and residents.
The rural/urban interface is characterised by multiple fuel types, including vegetation, as well as a range of combustible materials from house structures, house contents, vehicles and other objects around a house. These burning materials are likely to emit additional toxic combustion products, and as a result may cause a greater health risk to firefighters and community members in the vicinity of the fire.
Tests on a small scale have been conducted on a range of materials present in buildings to assess the type and yield of a range of emission products. Furthermore, large scale fire tests have been conducted to assess emissions from car fires and fires within a specific room. A review of the existing literature has revealed that organic compounds were considered to present a potential health hazard, but in most studies individual compounds have either not been identified or quantified. Although total emissions of carbon monoxide (CO) and carbon dioxide (CO2) dominate, hydrocarbons and volatile organic compounds are important contributors to the total emissions, and therefore likely to impact on health.
What Research Has Been Done?
Experimental burns were conducted using a cone calorimeter, which is a small-scale fire test apparatus that aims to determine heat release rate, mass loss rate, ignitability, gas species and particle production rate. Specimens sized 100mm by 100mm of various building types and furnishings were conditioned at 23°C and 50 percent relative humidity. The specimens were then placed into a sample holder and subjected to a radiant heat source of 25 kW/m2. The tests were conducted in well-ventilated conditions with constant air supply fed into the system. The gases passed through an exhaust duct, which was lined with two sampling inlets. These were linked to a number of sampling devices to collect a range of gaseous species and particles.
A desktop study on toxic emissions from fires at the rural/urban interface has shown that wood and wood-based products make up the majority of materials burnt, followed by polymeric materials. As such, the materials tested in the experimental burns included a number of wood-based and polymeric products commonly found in furnishings and home contents. Most of these materials were predominantly made up of carbon, oxygen and hydrogen. Because of this, their major emissions are CO2 and CO. However not all of the carbon is converted to CO2 and CO; the carbon that is not is released as aliphatic, aromatic and oxygenated hydrocarbons, some of which have the potential to harm people's health.
Some of the materials such as particleboard, medium-density fibreboard, carpet and polyurethane foam contain a significant fraction of nitrogen. Burning these materials will produce hydrogen cyanide, ammonia, nitriles and nitrogenated hydrocarbons. All of these are potentially harmful to people's health.
Emissions from all materials tested were evaluated against those from pine, a natural material widely used for structural construction. For this reason, it is a good reference material against which to compare manufactured and/or synthetic materials.
What Has Been Learnt?
Initial findings from the experimental burns, as well as the literature review conducted prior to the tests, show that exposures to compounds emitted during combustion of materials can lead to a range of adverse health impacts. These can be classified as follows:
1 Asphyxiants (CO and hydrogen cyanide).
2 Irritants (particles, volatile organic compounds, carbonyls, nitrogen dioxide, ammonia, hydrogen chloride and sulphur dioxide).
3 Impact on the central nervous system (CO, benzene, toluene, phenol).
4 Carcinogens (benzene, formaldehyde, naphthalene, isocyanates).
Some of these toxins, in particular chlorinated and nitrogenated compounds, are likely to be more present in bushfires at the rural/urban interface due to the types of fuels and materials burnt when compared with a forest bushfire. Other air toxins such as CO, particulate matter, formaldehyde and benzene are major air toxins emitted from both rural/urban interface and forest bushfires.
The results from the experimental burns are summarised in Figures 1 and 2, which show the emission factors (defined as the amount of a compound emitted per amount of fuel consumed) of CO, CO2, particulate matter, elemental carbon, organic carbon, and the elemental carbon to organic carbon ratio for 11 different types of combustible materials. Figure 3 shows the total carbonyls for these same materials. Results from a previous study that measured CO and CO2 emissions for CCA treated pine are included as a reference in Figure 1.
The highest emission factors of CO were observed for polystyrene, followed by plasterboard, particleboard with melamine and polyester (Figure 1). In comparison, pine recorded the lowest emission factors.
Fine Particulate Matter
The highest emission factors of fine particulate matter were measured for polyester and polystyrene (Figure 2). Both materials emitted approximately 20 times more particles compared with pine, while carpet emitted approximately nine times more particulate matter than pine. No major differences were observed among wood-based products.
Elemental Carbon & Organic Carbon
Wood-based materials were found to have the lowest carbon emissions, while polyester, carpet and polystyrene had the highest (Figure 2).
In general there was a larger fraction of elemental carbon compared with organic carbon. The exception was with polystyrene and plasterboard, where a significant organic carbon fraction was recorded. Lower elemental carbon to organic carbon ratios were also observed for manufactured wood products when compared with pine, with the difference likely due to the presence of glues and resins in the manufactured products. The organic fraction is likely to contain harmful organic compounds.
Carbonyls
Carbonyls, a class of irritating volatile compounds, were emitted at highest concentrations during combustion of polystyrene, with emission factors for total carbonyls being 45 times higher than those for pine. Other materials with high emissions of carbonyls were plasterboard, polyester and polyurethane foams.
The relative distribution of individual carbonyls for each material is shown in Figure 3. It clearly shows, with the exception of polystyrene, that formaldehyde and acetaldehyde were the dominant carbonyls, contributing between 29 percent and 93 percent to the total emissions of carbonyls. Formaldehyde is a known human nasal carcinogen, while acetaldehyde is a possible human carcinogen. For the combustion modified polyurethane foam, acetaldehyde was the dominant carbonyl (80 percent). Both polystyrene and carpet had significant emissions of the strong irritant benzaldehyde. Acrolein, another strong irritant, was emitted primarily during combustion of wood-based products.
About two to four times the amount of emissions were observed for manufactured wood products compared with pine. A wide range of volatile organic compounds were identified during testing. These can have health effects that range from irritation of the eyes, skin, nose, throat and respiratory system, to headaches, dizziness, drowsiness and nausea, to being possible and known human carcinogens.
While a number of volatile organic compounds (benzene, toluene, styrene, xylenes, naphthalene, acetic acid and phenol) were present during combustion of all materials, others have only been identified during combustion of specific materials. These include pyrrole and nitriles, which were emitted during combustion of nitrogen containing materials only (particleboard, medium-density fibreboard, carpet) and pinene, camphene and limonene, which were emitted solely from combustion of wood-based materials. In general burning wood-based and polymeric materials released volatile organic compounds at higher concentrations than pine. As a result, the combustion of these products in fires at the rural/urban interface is likely to present a greater health risk than forest bushfires.
How Could the Research be Used?
The research will provide a better understanding of exposure risks to personnel and communities during bushfires that extend into the rural/urban interface.
The emphasis for assessing this exposure risk is on inhalation – exposures that occur outside of burning structures at varying distances from the fire and the smoke plume. It is assumed that in most cases firefighters do not wear breathing apparatus and that the majority of firefighting will be done outdoors. This clearly distinguishes firefighting at the rural/urban interface from firefighting at structural fires.
The outcomes from the research can be used to inform training, work practices and appropriate use of personal respiratory protective equipment, as well as to assess the use of truck-mounted air monitoring devices and to provide advice on firefighter and community safety.
Where to Now?
The emission factors determined during the small-scale experimental burns described in this article are not necessarily representative of all exposures firefighters could encounter. However, they do provide an important input into a high time-resolution dispersion model that will provide short-term modelled ground concentrations, resulting in a reliable estimate of potentially hazardous exposures.
Significant additional work is required to develop a useable set of scenarios and compare modelled exposure concentrations with previously measured exposures at structural fire incidents. Monitoring was conducted at structural training fires, which simulated room fires in three typical rooms (living room, bedroom and office). The results will provide data to validate outputs from the model.
Dr Fabienne Reisen is Bushfire CRC project leader and Research Scientist at CSIRO Marine & Atmospheric Research
For more information, go to www.bushfirecrc.com
Tell, Show, Do – the Delivery of Effective ARFF Training
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How accurate is capsule endoscopy for detecting colorectal polyps and cancer in adults with known or suspected colonic disease?
Blinded comparison of capsule endoscopy and colonoscopy. ClinicalTrials.gov NCT00604162.
8 centers in Belgium, France, Germany, Italy, Spain, and the UK.
332 adults (mean age 59 y and 55% men based on 320 patients analyzed), who were scheduled to have colonoscopy because of known colonic disease in patients ≥ 18 years of age or suspected colonic disease in patients ≥ 50 years of age. Exclusion criteria included dysphagia, congestive heart failure, renal insufficiency, intestinal obstruction, abdominal surgery in the past 6 months, life-threatening conditions, use of implantable electromedical devices, and pregnancy.
Capsule endoscopy using ingestible PillCam COLON capsules, which have an endoscope with an imager at each end. Patients ingested capsules after colon preparation without colon insufflation or sedation. Capsules were naturally excreted.
Optical colonoscopy for polyp detection and colonoscopy plus biopsy for detection of adenomas and cancer.
Included sensitivity and specificity for detecting colonic polyps, advanced adenomas (size ≥ 1 cm or with villous features or high-grade dysplasia), and carcinomas.
Capsule endoscopy had low-to-moderate sensitivity for detecting polyps, advanced adenomas, and cancer; specificity was high for polyps and advanced adenomas ≥ 10 mm and low for cancer and smaller polyps and advanced adenomas (Table).
In patients with known or suspected colonic disease, capsule endoscopy had low sensitivity but high specificity for detecting large polyps and advanced adenomas; accuracy for detecting colorectal cancer was limited.
‡Gold standard = colonoscopy plus biopsy.
Published: Ann Intern Med. 2009;151(10):JC5-11.


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Efficacy and Safety of Everolimus in Korean Patients with Metastatic Renal Cell Carcinoma Following Treatment Failure with a Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor
Cancer Res Treat. 2014;46(4):339-347
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Publication date (electronic) : 2014 July 16
doi : https://doi.org/10.4143/crt.2013.154
Kwonoh Park, MD1,2,3, Jae-Lyun Lee, MD, PhD,1,2, Jin-Hee Ahn, MD, PhD1,2, Kyoo Hyung Lee, MD, PhD2,4, In-Gab Jeong, MD, PhD5, Cheryn Song, MD, PhD5, Bumsik Hong, MD, PhD5, Jun Hyuk Hong, MD, PhD5, Hanjong Ahn, MD, PhD5
1Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
3Department of Hematology-Oncology, KEPCO Medical Center, Seoul, Korea
4Departments of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
5Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Correspondence: Jae Lyun Lee, MD, PhD Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Tel: 82-2-3010-5977 Fax: 82-2-3010-6961 E-mail: jaelyun@amc.seoul.kr
Received 2013 August 23; Accepted 2013 October 15.
The purpose of this study is to assess the efficacy and safety of everolimus in Korean patients with metastatic renal cell carcinoma (mRCC) for whom initial treatment with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) has failed.
Eligible patients with mRCC (any histology) who had progressed on or were intolerant of VEGFr-TKI therapy received oral everolimus (10 mg dose once daily). Tumor response was reassessed according to Response Evaluation Criteria in Solid Tumors (RECIST).
This study included 100 patientswith a median follow-up duration of 10.2 months, a median progression-free survival (PFS) of 4.2 months (95% confidence interval [CI], 3.4 to 5.0 months), and an overall survival of 10.1 months (95% CI, 6.9 to 13.3 months). The most common grade 3 or greater adverse events (AEs) overall were anemia (13%), pneumonitis (9%), hyperglycemia (8%), and stomatitis (6%). While the incidence of pneumonitis was similar (26 cases, 26%) to the reported incidence in Western patients, the Korean presentations were more severe: 10 patients permanently discontinued everolimus due to pneumonitis, including two deaths on treatment. Statistically significant relationships were established between biologic toxicities, hyperglycemia and anemia, and PFS (hyperglycemia vs. non-hyperglycemia: hazard ratio [HR], 0.61; p=0.055 and anemia vs. non-anemia: HR, 0.51; p=0.021).
Everolimus was effective in Korean patients with mRCC who had failed initial VEGFr-TKI therapy. While everolimus was well tolerated in general and the AE incidence of this study was similar to those of previous reports, severe pneumonitis was common. Hyperglycemia and anemia showed significant correlation with PFS and thus may be potentially useful as prognostic indicators.
Keywords: Renal cell carcinoma; Everolimus; Treatment outcome; Safety
Treatment of metastatic renal cell cancer (mRCC) has changed significantly over the past few years following the introduction of targeted agents that inhibit elements of the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways [1-7]. Based on highest level of evidence, current practice guidelines recommend sunitinib, pazopanib, and bevacizumab plus interferon alpha as first-line therapies for mRCC patients who are of favorable or intermediate risk [2,5,7], and temsirolimus for mRCC patients who are of poor risk [3].
Despite the documented benefits of these newer agents, complete responses (CR) are rare, with most patients eventually becoming resistant to treatment after a median of 6-11 months [1,2,5-9]. Based on positive results from the phase III RECORD-1 and AXIS trials, clinical guidelines have recommended the use of everolimus, an mTOR inhibitor, or axitinib, a new vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI), in mRCC cases refractory to VEGFr-TKIs [2,10]. Previously, our team demonstrated a comparable efficacy of sequential VEGFr-TKI versus mTOR inhibitor as a second-line therapy after an initial VEGFr-TKI failure [11]. In the study, the progression-free survival (PFS) was three months for both groups and overall survival (OS) was also similar at 10.6 and 8.2 months, respectively [11]. Similarly, a phase III INTORSECT trial comparing temsirolimus and sorafenib as a second-line treatment for mRCC after sunitinib failure showed that the PFS, the primary endpoint, did not differ significantly between treatment cohorts, while OS showed unexpected improvement in patients treated with sorafenib [12].
Due to drug availability and the reimbursement policies of the National Health Insurance program in Korea, the majority of patients receive everolimus as a second-line systemic therapy following a first-line VEGFr-TKI failure. However, few studies investigating the actual efficacy and safety of everolimus as a second-line targeted therapy for mRCC have been reported, particularly in patients with Asian ethnicity [13,14]. Thus, the aim of the current study is to assess the efficacy and safety of everolimus as a second-line targeted therapy in Korean mRCC patients who failed on VEGFr-TKI. Additional evaluations included an assessment of prognostic factors associated with disease progression and correlation analyses between everolimus-associated adverse events (AEs) and clinical efficacy.
1. Patient population
A database of mRCC cases who received VEGFr-TKI therapy at the Asan Medical Center from April 2006 was constructed. Of these, patients with an evaluable lesion who had been treated previously with VEGFr-TKI (sunitinib, sorafenib, or pazopanib) and who received everolimus sequentially due to intolerability or disease progression were enrolled in this study. Patients treated with two or more VEGFr-TKIs or who received immunotherapy (interleukin-2, interferon) and/or chemotherapy were included. Patients with central nervous system metastases, a Karnofsky performance scale (KPS) score of 50-60, and an uncontrolled medical condition (such as heart failure or diabetes) were also included in the analysis. Patients with a baseline KPS ≤ 40 and prior treatment with another mTOR inhibitor (e.g., temsirolimus) were excluded from analysis. Patients who were lost to follow up during the first two weeks without evidence of disease progression were also excluded.
2. Treatment and data collection
Everolimus at a dose of 10 mg was administered orally once daily. Dose delays and dose modifications were performed in accordance with the everolimus package insert. Comprehensive clinical, laboratory, and radiologic data were collected and reviewed in order to optimize the accuracy and completeness of the patient information in the database following the initiation of everolimus treatment. Patients were primarily followed through outpatient clinic appointments every 2-4 weeks. Physical examination, laboratory testing, and AEs assessment were performed at each visit. The tumor response was assessed every 6-8 weeks during follow-up. Responses were independently reassessed by two investigators (K.P. and L.J.L) using Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1 [15]. AE severity was categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) ver. 4.0 [16]. When AEs were present at baseline, the change in AE grade from baseline to follow-up was used to assess the safety of everolimus. This study was approved by the Institutional Review Board of Asan Medical Center, which waived the requirement for patient informed consent due to its retrospective design.
3. Statistical analysis
Summary characteristics and descriptive statistics of the study population are reported as proportions and medians. PFS was defined as the time from everolimus initiation until either first documentation of RECIST-defined disease progression or death due to any cause, whichever came first. OS was defined as the time from everolimus initiation until death from any cause. Kaplan-Meier estimates were used for analysis of the PFS and OS values. Univariate and multivariate analyses using Cox proportional hazards regression were performed for determination of clinical prognostic factors associated with the PFS and/or OS.
A primary multivariate model was developed and analyzed, which first incorporated basic clinical factors. Previous VEGFr-TKI-related factors (i.e., response to and treatment duration of initial VEGFr-TKI, number of previous VEGFr-TKIs) and everolimus-associated AE development were then reanalyzed individually in the primary multivariate model. All statistical analyses were two-sided and were performed using SPSS ver. 19.0 (SPSS Inc., Chicago, IL); p < 0.05 were accepted as statistically significant.
1. Baseline characteristics
Among the pooled database of 376 patients with mRCC who were treated with a targeted agent, 113 consecutive patients received everolimus. Of these 113 patients, 8 cases were excluded from this study because they had received everolimus as a first-line therapy. Other exclusions included two patients with a KPS of ≤ 40, three patients who were lost to follow up within the first two weeks without documented evidence of disease progression, and one patient did not have an evaluable lesion. In total, 100 patients were included in these analyses.
Patient baseline characteristics are shown in Table 1. The median patient age was 58.1 years (range, 29 to 83 years) and 84% of the subjects had undergone a prior nephrectomy. Of the 95 patients who could be assessed using all topics covered under Heng's criteria, eight patients had a favorable risk, 64 had intermediate risk, and 23 were at high risk [17]. The initial VEGFr-TKI was sunitinib (n=73), sorafenib (n=17), or pazopanib (n=10). Eighty-one patients (81%) had received one prior VEGFr-TKI therapy, while the remaining 19 patients had undergone prior treatment with two different VEGFr-TKIs. Twenty patients (20%) had previously received an immunotherapy for mRCC. The median treatment duration of initial VEGFr-TKI was 9.2 months (range, 0.9 to 61.7 months) and 89 patients progressed during their VEGFr-TKI treatment. The remaining 11 patients discontinued VEGFr-TKI treatment mainly due to drug intolerance and nine of 11 patients experienced disease progression within six months of their last VEGFr-TKI dose.
Characteristics of Korean mRCC patients
2. Treatment administration and safety
At the time of analysis (October 2012), 16 patients were being treated with everolimus and the remaining 84 patients had been taken off this treatment, with a median treatment duration of 4.0 months (range, 0.5 to 30.9 months). Reasons for treatment discontinuation included disease progression (n=63), everolimus-associated AEs (n=12), and other reasons (n=9).
The AEs most frequently associated with everolimus were anemia (80%), hypercholesterolemia (62%), hyperglycemia (56%), asthenia (47%), stomatitis (44%), and pneumonitis (26%). The most commonly reported grade 3/4 AEs were anemia (13%), pneumonitis (9%), hyperglycemia (8%), and stomatitis (6%) (Table 2). In total, 11% of everolimus-treated patients required at least one dose reduction. Among the 12 patients who discontinued everolimus due to treatment-related AEs, 10 patients were diagnosed with pneumonitis (two cases were grade 5), one with bacterial pneumonia and one with stomatitis. Of 84 patients who discontinued everolimus, 50 patients (60%) could not receive subsequent alternative therapy after discontinuation.
Adverse events for everolimus in mRCCa)
3. Efficacy
Of the 99 patients with measurable lesions, there were no CR. Three patients (3%) achieved a confirmed response, 68 (68%) had stable disease, and 25 (25%) had progressive disease (PD). The remaining patient with a non-measurable lesion was categorized as non-CR/non-PD. Thus, the calculated disease control rate (DCR) was 72% (Table 3). With a median follow-up duration of 10.2 months (95% confidence interval [CI], 7.9 to 12.7 months), the median PFS on everolimus was 4.2 months (95 % CI, 3.4 to 5.0 months) and the median OS was 10.1 months (95 % CI, 6.9 to 13.3 months) (Fig. 1).
Response to everolimus in Korean mRCC patients for whom VEGFr-TKI treatment failed
Progression-free survival and overall survival in metastatic renal cell carcinoma patients treated with everolimus.
4. Pretreatment factors showed correlation with everolimus efficacy
Results of univariate analysis showed significant association of young age (< 60 years, p=0.018) and a short time from initial diagnosis to first-line VEGFr-TKI treatment (< 1 year, p=0.003) with a poor PFS. The number of metastatic sites (n ≥ 2, p=0.063), lactate dehydrogenase level (> upper limit of normal, p=0.106), and Heng's criteria (favorable vs. poor, p=0.080; intermediate vs. poor, p=0.007) were found to show marginal correlation with the PFS. In multivariate analysis, with the exception of patient age, no pretreatment factors showed independent association with the PFS (Table 4). Regarding OS, results of univariate analysis showed significant association of a short time from initial diagnosis to first-line VEGFr-TKI treatment (< 1 year, p=0.015) and an increased number of metastatic lesions (≥ 2, p=0.009) with poor OS. In addition, KPS (≤ 70, p=0.029), serum-corrected calcium level (> upper limit of normal, p=0.003), and Heng's criteria (favorable vs. poor, p=0.017; intermediate vs. poor, p < 0.001) also showed statistically significant associations. Most of the significant factors from the univariate analysis also remained significant in the multivariate analyses. Heng's criteria could be used in prediction of the OS in multivariate analysis (favorable vs. poor: HR, 0.09; p=0.014 and intermediate vs. poor: HR, 0.40; p=0.005) (Table 4).
Multivariate analysis of prognostic factors predictive of progression-free survival and overall survival in Korean RCC cases (primary multivariate model)a)
5. Efficacy of everolimus with prior TKI therapy
Clinical outcomes (PFS and OS) for patients treated with everolimus were also analyzed according to response to initial VEGFr-TKI, duration of initial VEGFr-TKI treatment, and number of VEGFr-TKIs used in prior therapy. In univariate analyses, primary refractory disease and a short initial VEGFr-TKI treatment duration (< 6 months, early resistance) showed significant correlation with poor prognosis, which was assessed by both PFS and OS (data not shown). When the univariate analyses excluded patients with primary refractory disease (n=24), short treatment duration was found to show significant correlation with a poor PFS and OS (< 6-month vs. > 6-month PFS: HR, 2.80; p=0.001 and < 6-month vs. > 6-month OS: HR, 2.75; p=0.008). However, number of previously used VEGFr-TKIs did not show correlation with clinical outcomes following everolimus therapy as assessed by both PFS and OS (data not shown).
When the factors related to previous VEGFr-TKI treatment were applied to the aforementioned primary multivariate analysis, a primary refractory response to initial VEGFr-TKI treatment showed significant correlation with poor prognosis as measured by both PFS and OS (PFS in the primary refractory group vs. disease control group: HR, 3.17; p=0.002 and for OS: HR, 4.75; p<0.001). A short duration of initial VEGFr-TKI treatment showed correlation with a poor PFS and OS in the primary multivariate analysis patients if primary refractory disease was excluded from the model (< 6-month vs. > 6-month PFS: HR, 2.62; p=0.028 and for OS: HR, 2.92; p=0.043).
6. Efficacy of everolimus based on AEs
To investigate the relationship between everolimus-associated AEs and antitumor efficacy, we evaluated possible associations between AEs (particularly frequent AEs such as anemia, lymphocytopenia, hyperglycemia, hypercholesterolemia, stomatitis, and pneumonitis) with PFS. Only development of hyperglycemia during everolimus treatment showed significant correlation with a favorable PFS (HR, 0.57; p=0.025), while anemia was only marginally significant (HR, 0.65; p=0.101) (Table 5). When these AEs were applied to the primary multivariate analysis, hyperglycemia showed a marginally significant correlation with a favorable PFS (hyperglycemia group vs. non-hyperglycemia group: HR, 0.58; p=0.056) and anemia showed significant correlation with an improved PFS (anemia group vs. non-anemia group: HR, 0.51; p=0.021).
Univariate analysis of progression-free survival based on adverse event developmenta)
The current study findings demonstrate the efficacy and safety of everolimus in Korean mRCC patients for whom a previous VEGFr-TKI therapy had failed. We also evaluated putative prognostic factors associated with favorable treatment outcomes. Our results are generally in line with those reported from the RECORD-1 phase 3 trial and from retrospective studies, however, the OS and safety features from the current data differ from those of previous reports [4,11,14]. Of particular interest, our findings indicate correlation of everolimus-associated anemia and hyperglycemia with improved clinical outcomes in mRCC, with significant benefits in terms of PFS. This result suggests that particular AEs may be potential biomarkers of everolimus treatment efficacy in mRCC.
Our current analyses also show PFS and OS outcomes of everolimus therapy at 4.2 and 9.1 months, respectively, and a DCR of 72%. Our PFS and DCR findings are similar to those reported for the phase 3 RECORD-1 trial, in which the activity of everolimus showed a median PFS of 4.9 months and a DCR of 65%, and of the REACT study, in which the activity of everolimus showed a DCR of 53% [14,18]. However, in our study, the OS outcome was poorer than that in earlier reports. This is likely because we included patients with brain metastases and a poor performance status, whereas previous reports have been of clinical trials with strict inclusion criteria. In addition, 59% of our patients did not receive any subsequent anti-tumor therapy after the discontinuation of everolimus. Some retrospective or subgroup analyses for evaluation of patients who had been previously treated with sunitinib and an mTOR inhibitor have shown that sorafenib or sunitinib retrials as third-line targeted therapies yielded a PFS range of 4-8 months and an OS range of 6-8.4 months [19,20]. Considering the substantial efficacy of third-line targeted therapies, the small proportion of patients who were able to receive such treatments would negatively impact the OS outcome.
Treatment responses and the duration of a previous VEGFr-TKI were found to show correlation with everolimus clinical outcomes. Specifically, patients who showed a poor response (primary refractory or short treatment duration) to initial VEGFr-TKI therapy also showed poor clinical outcomes with everolimus, even though this agent targets a different cellular pathway. This finding is consistent with those of a previous study, which demonstrated generally poor responses to second-line therapy, regardless of whether a VEGFr-TKI or an mTOR inhibitor was administered to patients with primary refractory disease [21]. As a possible explanation for these results, treatment resistance may be driven largely by pathways independent of VEGF and/or mTOR in cases of poor response to initial VEGFr-TKI therapy.
Heng's criteria, which is the prognostic model of the International Metastatic Renal Cell Carcinoma Database Consortium for patients who receive first-line VEGF pathway inhibitors, has also proven useful for prediction of OS in mRCC patients who received everolimus after VEGFr-TKI failure [17]. However, in the current analyses, the hematologic components of Heng's criteria, including the hemoglobin level, neutrophil count, and platelet count, were found not to be significant predictors of either PFS or OS. In contrast, we found that KPS, time from initial diagnosis to first-line VEGFr-TKI treatment, and the corrected calcium level showed significant correlation with OS. These results differ from those of the phase III RECORD-1 trial, which reported significant association of both the hemoglobin level and neutrophil count with OS [18]. However, our study was conducted in a real practice setting administering second-line everolimus without a substantial time interval and is therefore unlikely to be comparable with other clinical trials that incorporated a time interval between a first-line TKI failure and subsequent treatment. Hence, pretreatment values, particularly hematologic values affected by a previous VEGFr-TKI therapy, may not accurately reflect the efficacy of subsequent treatments.
In the current study, the everolimus AE profile was generally similar to that reported from previous phase III studies [14,18]. Asthenia, stomatitis, anemia, hyperglycemia, and hypercholesterolemia were the most common AEs, whereas severe AEs of grade 3 or 4 were overall rare. Of note, our study included 26 cases of pneumonitis (26%), among whom 10 patients permanently discontinued everolimus therapy and two patients died due to pneumonitis. Our results thus indicate that both the proportion and the severity of pneumonitis was higher than previously reported from large studies such as RECORD-1 and REACT, which reported pneumonitis incidence of 14% and 6%, respectively [14,18]. However, White et al. [22], who reported a 14% incidence of clinical pneumonitis, found a 39% incidence in patients receiving everolimus for mRCC via a careful chest imaging re-analysis of RECORD-1. In another retrospective study, Dabydeen et al. [19] reported a 30% incidence of pneumonitis after mTOR inhibitor therapy as assessed by independent radiologic review. As diagnosis of pneumonitis is based on a constellation of radiologic image findings in conjunction with clinical symptoms, and because differentiation of pneumonitis from infectious pneumonia or progression of a lung metastasis is not easy, its incidence may vary between studies. Some AEs, which were easily detected using standard laboratory evaluations such as those for anemia, hyperglycemia, or hypercholesterolemia, have reported incidences similar to those described in other large clinical trials. Therefore, our current results suggest that Korean patients with mRCC might show an AE incidence similar to that of Western patients, however, pneumonitis can cause more serious consequences for these cases, such as drug interruption or death.
We analyzed everolimus efficacy in relation to associated AEs. With the exception of stomatitis, patients with AEs tended to experience a more favorable PFS compared to subgroups without AEs. Of these AEs, hyperglycemia and anemia showed correlation with a favorable PFS, similar to the identification of hypertension as a biomarker for VEGFr-TKI and rash as a biomarker for EGFR-TKI [21,23,24]. These findings support the hypothesis that everolimus-associated AEs may indicate a favorable prognosis after everolimus treatment in this patient population. Dabydeen et al. [19] reported that patients with pneumonitis show a more favorable prognosis than those without pneumonitis in receiving an mTOR inhibitor. However, according to our current results, development of pneumonitis did not show correlation with a favorable prognosis. Further investigations are thus needed in order to confirm which AEs are specifically associated with everolimus and to perform time dependent analysis to address the possibility that patients treated with everolimus for an extended period of time may experience additional AEs. In consideration of the favorable prognostic trends of these everolimus-associated AEs, early recognition and prompt intervention for severe AEs may help patients to achieve uninterrupted full-dose therapy with everolimus, and therefore further opportunities for improvement of clinical outcomes.
Some limitations of our current study included the use of data from a single center, its retrospective nature with possible selection bias, and some missing data. However, our current data are the first of their kind from a Korean population and are based on a larger sample size than any previous reports from Asia. In addition, unlike the populations in clinical trials, which are stringently selected and are based on effectiveness, our current study included patients who had brain metastases or a poor performance status. Thus, our current study reflects a real-world experience with everolimus and has relevance in daily clinical practice.
Everolimus is an effective treatment in Korean mRCC patients for whom initial VEGFr-TKI therapy has failed. AEs were present in our Korean patients at a frequency comparable to those reported from Western countries, while they tended to be more severe and to lead to permanent discontinuation of the drug, particularly in cases of pneumonitis. AEs such as hyperglycemia and anemia correlate with a favorable prognosis and may represent potential biomarkers of everolimus efficacy in patients with mRCC.
Conflict of interest relevant to this article was not reported.
This study was supported in part by a grant (no.HI12C17880300) from the Korean Health Technology R&D Project, Ministry of Health and Welfare, and a grant (no. 2013K000281) from the Converging Research Center Program of the Ministry of Science, ICT, and Future Planning, Republic of Korea.
1. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356:125–34.
2. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007;370:2103–11.
3. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271–81.
4. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449–56.
5. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115–24.
6. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 2008;26:5422–8.
7. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28:1061–8.
8. Patel PH, Senico PL, Curiel RE, Motzer RJ. Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma. Clin Genitourin Cancer 2009;7:24–7.
9. Feldman DR, Baum MS, Ginsberg MS, Hassoun H, Flombaum CD, Velasco S, et al. Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 2009;27:1432–9.
10. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus so-rafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011;378:1931–9.
11. Park K, Lee JL, Park I, Park S, Ahn Y, Ahn JH, et al. Comparative efficacy of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor as second-line therapy in patients with metastatic renal cell carcinoma after the failure of first-line VEGF TKI. Med Oncol 2012;29:3291–7.
12. Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman K, et al. Temsirolimus versus sorafenib as second line therapy in metastatic renal cell carcinoma: results from the INTORSECT trial. Ann Oncol 2012;23(Suppl 9):Absr LBA22.
13. Tsukamoto T, Shinohara N, Tsuchiya N, Hamamoto Y, Maruoka M, Fujimoto H, et al. Phase III trial of everolimus in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from RECORD-1. Jpn J Clin Oncol 2011;41:17–24.
14. Grunwald V, Karakiewicz PI, Bavbek SE, Miller K, Machiels JP, Lee SH, et al. An international expanded-access programme of everolimus: addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy. Eur J Cancer 2012;48:324–32.
15. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228–47.
16. National Cancer Institute. Common terminology criteria for adverse events (CTCAE). Version 4.0. Bethesda: National Institutes of Health, US Department of Health and Human Services; 2009.
17. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 2009;27:5794–9.
18. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer 2010;116:4256–65.
19. Dabydeen DA, Jagannathan JP, Ramaiya N, Krajewski K, Schutz FA, Cho DC, et al. Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic renal cell carcinoma: incidence, radiographic findings and correlation with clinical outcome. Eur J Cancer 2012;48:1519–24.
20. Zama IN, Hutson TE, Elson P, Cleary JM, Choueiri TK, Heng DY, et al. Sunitinib rechallenge in metastatic renal cell carcinoma patients. Cancer 2010;116:5400–6.
21. George S, Reichardt P, Lechner T, Li S, Cohen DP, Demetri GD. Hypertension as a potential biomarker of efficacy in patients with gastrointestinal stromal tumor treated with suni-tinib. Ann Oncol 2012;23:3180–7.
22. White DA, Camus P, Endo M, Escudier B, Calvo E, Akaza H, et al. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med 2010;182:396–403.
23. Rini BI, Cohen DP, Lu DR, Chen I, Hariharan S, Gore ME, et al. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 2011;103:763–73.
24. Perez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, et al. Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol 2004;22:3238–47.
Article information Continued
Copyright © 2014 by the Korean Cancer Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Median age (range, yr) 58.1 (29-83)
Male 80 (80)
Female 20 (20)
Tumor histology
Clear cell type 86 (86)
Non-clear cell type 14 (14)
Any sarcomatoid features (n=84, nephrectomy cases)
Yes 10 (10)
No 74 (74)
Initial VEGFr-TKI therapy
Sunitinib 73 (73)
Sorafenib 17 (17)
Pazopanib 10 (10)
No. of previous VEGFr-TKI therapies
1 81 (81)
≥ 2 19 (19)
100-90 22 (2)
80-70 74 (74)
Previous nephrectomy
Previous immunotherapy
No. of metastatic sites
≤ 1 16 (16)
Heng's criteriaa)
Favorable 8 (8)
Intermediate 64 (64)
Poor 23 (23)
Not applicable 5 (5)
mRCC, metastatic renal cell carcinoma; VEGFr-TKI, vascular endothelial growth factorreceptor-tyrosine kinase inhibitor; KPS, Karnofsky performance scale.
Heng's prognostic criteria: low KPS score < 80, low hemoglobin (< lower limit of normal), high corrected serum calcium concentration (> upperlimit of normal), high platelet count (> upper limit of normal), high neutrophil count (> upper limit of normal), time from diagnosis to treatment < 1 year. Categories are defined as favorable=0, intermediate=1-2, or poor=3-6 risk factors.
≥ Grade 3
Non-hematologic
Diarrhea 11 (12) 0
Asthenia 45 (47) 0
Nausea 23 (24) 0
Vomiting 6 (6) 0
Stomatitis 42 (44) 6 (6)
Rash 30 (32) 1
Peripheral edema 7 (7) 1
Pain 23 (24) 1
Hemorrhage 13 (14) 1
Pneumonitis 26 (27) 9 (9)
Infection (pneumonia) 7 (7) 2 (2)
Hemoglobin decreased 76 (80) 12 (13)
Neutrophil decreased 15 (16) 0
Thrombocytopenia 33 (35) 3 (3)
Lymphocytopenia 27 (28) 3 (3)
Laboratory values
Glucose increased 53 (56) 8 (8)
Cholesterol increased 58 (61) 1 (1)
Creatinine increased 17 (18) 1 (1)
AST increased 39 (41) 1 (1)
ALT increased 24 (25) 0
Bilirubin increased 3 (3) 0
Values are presented as number (%). mRCC, metastatic renal cell carcinoma; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
The safety population (95 cases) included patients who received safety assessment of one or more following the initiation of everolimus therapy.
Response No. (%)
Complete response 0
Partial response 3 (3)
Stable disease 69 (69)
Progressive disease 25 (25)
mRCC, metastatic renal cell carcinoma; VEGFr-TKI, vascular endothelial growth factor-tyrosine kinase inhibitor.
Variable Progression-free survival
Hazard ratio p-value Hazard ratio p-value
Age (≥ 60 yr vs. < 60 yr) 0.57 0.033 0.58 0.098
Gender (male vs. female) 0.83 0.534 1.01 0.972
Histology (non-clear vs. clear) 1.29 0.479 0.85 0.699
Prior nephrectomy (no vs. yes) 1.46 0.217 1.53 0.251
No. of metastatic sites (≥ 2 vs. ≤ 1) 1.79 0.134 2.81 0.037
Type of first VEGFr-TKI
(sorafenib vs. non-sorafenib) 0.76 0.473 1.86 0.162
Heng's criteriab)
(favorable vs. poor) 0.46 0.164 0.12 0.014
(intermediate vs. poor) 0.55 0.023 0.39 0.003
RCC, renal cell carcinoma; VEGFr-TKI, vascular endothelial growth factor-tyrosine kinase inhibitor.
Primary multivariate model analysis was performed for evaluation of basic clinical factors, excluding previous VEGFr-TKI-related factors and development of everolimus-associated adverse event,
Heng's prognostic criteria: low Karnofsky performance scale (KPS) score < 80, low hemoglobin (< lower limit of normal), high corrected serum calcium concentration (> upper limit of normal), high platelet count (> upperlimit of normal), high neutrophil count (> upperlimit of normal), time from diagnosis to treatment < 1 year. Categories are defined as favorable=0, intermediate=1-2, or poor=3-6 risk factors.
Variable Hazard ratio 95% CI p-value
Anemia (yes vs. none) 0.63 0.38-1.08 0.095
Lymphocytopenia (yes vs. none) 1.01 0.62-1.64 0.972
Hypercholesterolemia (yes vs. none) 0.64 0.40-1.03 0.067
Hyperglycemia (yes vs. none) 0.60 0.37-0.97 0.038
Stomatitis (yes vs. none) 1.08 0.68-1.70 0.752
Pneumonitis (yes vs. none) 1.03 0.63-1.69 0.911
CI, confidence interval.

redpajama_set_name: RedPajamaCommonCrawl


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text:
Armes may refer to:

People
Armes (surname)
Armes Beaumont (1842–1913), English-born vocalist active in Australia

Places
Armes, Nièvre, commune in France

redpajama_set_name: RedPajamaWikipedia


text:
Q: How to render Django forms.ChoiceField as Twitter Bootstrap dropdown What is the most efficient way (in terms of programming/maintenance effort, elegance) to render a Django forms.ChoiceField as a Twitter Bootstrap dropdown using one of the django-bootstrap, django-bootstrap-form, django-bootstrap-toolkit, django-crispy-forms, etc apps? Is there explicit support for this use case in any of these apps?

A: Disclaimer I'm the lead developer of <a href="https://github.com/maraujop/django-crispy-forms/"django-crispy-forms (one of the apps mentioned).
I will try to explain how you do this with django-crispy-forms. You simply do in your template:
{% load crispy_forms_tags %}
{{ form|crispy }}

You can see this and more in django-crispy-forms docs. Your ChoiceField will be rendered as Bootstrap dropdown as you want.
Compared to django-bootstrap
First, a little bit of history. django-bootstrap was born after django-uni-form (the parent project from which django-crispy-forms evolved). At that time, django-uni-form was already doing Boostrap forms, but probably not in the best possible way (Bootstrap was supported by using an aditional contrib application). Thus, the author of django-bootstrap probably decided to go on its own.
Now, regarding Bootstrap support. django-bootstrap can also render forms but, instead of using a Django filter, it changes the base class of your form. So django-crispy-forms affects your templates while django-bootstrap affects your Python code.
Also, both django-crispy-forms and django-bootstrap let you do layouts. In django-bootstrap, layouts are in a Meta class within the form while in django-crispy-forms the layouts live in a subclass of FormHelper, which gives you decoupling.
django-bootstrap uses a tuple for defining a layout, while crispy-forms uses a subclass of Layout. This adds the possibility to reuse layouts, compose layouts easily, etc. Note that although crispy's encapsulation still has a list of fields inside, it adds a helpful and human-friendly API to programmatically manipulate the layout and I think enforces a good decoupling pattern.
From what I can see, layouts in crispy-forms are more powerful. It has a larger layout object collection, for example, prepended text, appended text, daterange and others are already supported while in django-boostrap these are in the TODO list.
crispy-forms has also an API for modifying layouts on the go and doing some hardcore programmatic layout building which is very nice.
crispy-forms also supports formsets of all kinds. It supports different CSS template packs, which means that if in the future the new kicking CSS pack is named 'chocolate', it will be very easy to create a new template pack for it and all your forms will be able to be rendered with 'chocolate' without code changes, just a simple setting variable.
crispy-forms also has attributes you can set in FormHelper that define nice extra functionaly you can easily turn on and off. You can also create your own custom attributes if you want.
Finally, django-crispy-forms (together with django-uni-form) has more than 67.000 downloads, which is quite good for a Django application. The project has almost 500 followers in Github, several big users, good testing coverage and several years of history and it's still actively maintained.
Compared to django-bootstrap-form
From what I can see django-bootstrap-form is only a filter for rendering a form with Bootstrap. That is something django-crispy-form covers while offering much, much more. The project was released on 21st August 2012 and looks to me like it's reinventing the wheel because several other apps cover already this use case.
Compared to django-bootstrap-toolkit
It's inspired by django-boostrap-form. From what I see in the docs, it also gives you a filter for rendering a form with Bootstrap. It apparently covers more Bootstrap stuff than forms, but  I can't find more info in its docs. Last commit was 2 months ago.

I will insist that I'm obviously not the right person for a comparison that is not biased. That's why I've never written about this before. I could have published a blog post about this several times but I always dismissed the idea. However, as the fragmentation of form apps (and bootstrap-support apps) is growing, I thought this might be a good time to write down what I think.

redpajama_set_name: RedPajamaStackExchange


text:
The Pit Review: A Heavy and Heavy-Handed Coming-of-Age Tale
In the dark coming-of-age tale "The Pit," narrow-minded rural Latvia seems as full of lurid secrets as Peyton Place, as well as being a locale where everyone has their nose in everyone else's business. Marking the feature debut of writer-director Dace Pūce (who co-wrote with Monta Gagane and Pēteris Rozītis), it's adapted from three stories by Latvian literary prize-winner Jana Egle. The action unfolds through the watchful eyes of an emotionally wounded boy stuck with his strict grandmother, but the film's odd tone, incompletely developed characters and uneven performances fail to match the poignancy of its source. Named as Latvia's submission for best international film, "The Pit" will premiere Stateside on Dec. 17 via streaming service Film Movement Plus.
Skinny, misunderstood 10-year-old Markus (Damirs Onackis) is unwillingly dispatched from Riga to the countryside following the death of his drug addict father, an artist. Flashbacks and gossip reveal that his mother left the family soon after he was born and wants nothing to do with him, so he falls to the care of his paternal grandmother Solveiga (Dace Eversa). But Solveiga is a long-time widow, busy with her garden and directing the community choir; she hasn't a clue how to handle her sullen, introverted grandson.
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Markus spends every free moment drawing, and his ambition is to earn a fortune by being a great artist. He resents being sent on make-busy projects by Solveiga, especially when they involve the company of his father's alcoholic cousin Roberts (Egons Dombrovskis, one of the film's weak acting links), who beats his meek wife Smaida (Polish thesp Agata Buzek, underused here). Roberts and Smaida live nearby with Solveiga's brother Alberts (Aigars Vilims), a mild man with unexplained issues in his past who is unable to do much about his son's brutality. The character arcs of these latter three are vastly underdeveloped and not as well connected with that of Markus as they could be.
As the narrative begins, Markus becomes persona non grata in the village because he abandons prissy neighbor Emilja (Luize Birkenberga) in the forest after she falls into a pit and cannot climb out. Emilja's mother Sandra (Inese Kucinska) is justly incensed and plots a campaign to declare the lad mentally ill and sent away. Given that a flashback showing events from Markus' perspective is placed quite late in the film, his behavior initially makes him a difficult protagonist to sympathize with.
While performing one of Solveiga's endless string of errands, Markus meets the mysterious hermit Sailor (Indra Burkovska), probably the film's most interesting character, who lives at the edge of the forest. Poking around Sailor's premises, Markus discovers an art project, a beautiful but incomplete stained-glass window. Soon, unbeknownst to Solveiga, he and his fellow loner are working together to finish it.
It's Sailor who delivers the line that is the film's leitmotif: "We all have our secrets." Indeed, the short stories in the book that the film is based on, "Into the Light," are predicated on bringing into view unspoken issues such as stigmatized sexuality, domestic violence, bullying and emotional trauma. But the film's screenplay fails to do much with or about the issues it exposes.
Likewise, the production design had a real opportunity to treat the forest at the edge of the village as a liminal space, a place between youth and experience, between belonging and being outcast, between naturalism and folktale. It gives some hints of trying, but it doesn't go far enough. Rather, the location is used more scenically and to give DP Gatis Grinbergs even more of a chance to play with dappled light, something he does at every opportunity.
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The untold truth of Gabby Barrett


It means it's a couple formally joining what years of practice have been working to cement. From my perspective, it doesn't feel like "it was all building to this!" more than "look at what we've made and are continuing to spend the time to make." Because A + R are already a team and have been before there was ever a white dress. All weddings are supremely special, true. But it's in the unmistakable intimacy (as well as the numerous inside jokes from which there was much laughter) that made this day extra everything.


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Star Wars Destiny in the works?
Any game added would be most appreciated!!
I try. Jim (nudge nudge) hasn't given me access to "The List" of games requested by users (at least not that I know of), so I'm kind of winging it. I work off of my own game library and the fact that I work in a game store (so I see new titles as they come in).
I plug away as I can, and am glad to contribute to the site!
I am a huge fan of two player games. Although they are new to me, it is great to see Symbaroum and The Creature That Ate Sheboygan added to the site.
More in the works?!? Awesome! I know it's a chore keeping up with all the new games, but I really appreciate when older games are added too. I've requested quite a few games, some of them on the older side (wink wink).
That would be me; I try to dig out some older titles as well as newer ones. I'm never quite sure as I add games to the pending list when they will go live.
I've got more in the works!
The thanks goes to Chris!
Jim, thanks for the update! It's always good to see an update, especially one with some older games. Wow, did you dig some of those games out of the woodwork!


The Chinese Historical Society of Southern California was founded in1975 to discover and recognize Chinese American pioneers and the history of Chinese Americans in Southern California. It also works to increase aware-ness of Chinese American heritage through public programs, education, and research. The society's holdings focus on Southern California Chinese American history. Its collections include three hundred transcriptions of oral history interviews with Southern Californian Chinese Americans, the Robert Nash Collection on Chinese junks and fisheries, artifacts from the Metropolitan Transportation Authority old Chinatown/Union Station excavation and the Santa Barbara Chinatown archaeological site, photographs of old Chinatown and China City, and three paintings of old Chinatown. Its archive contains extended summaries of the oral history interviews and a number of original documents. Some of the society's holdings are on display at the Chinatown Heritage and Visitors Center (411 Bernard Street).
This reference collection is about the history and culture of California. Contains over 20,000 books, magazines, newspaper, and pamphlets. The collection is a non-circulating resource collection of materials about Southern California in particular with a heavy emphasis on Los Angeles County, including individual cities and unincorporated areas. Fiction by major California writers is included as well as historical fiction about California.


text:
Illusions in Motion
Illusions in Motion: Media Archaeology of the Moving Panorama and Related Spectacles
By Erkki Huhtamo.
Boston, MIT Press, $45.00
Reviewed by Russell A. Potter
The paramount mass-media attraction of its era, the 'moving panorama' has, until now, received only piecemeal treatment; cast in the shadow of its larger brother, the fixed, 360-dgree panorama, it has generally been regarded as an historical side-note. There have been studies of moving panoramas of certain subjects -- such as my own Arctic Spectacles -- and some of particular regions, such as Mimi Colligan's Canvas Documentaries: Panoramic Entertainment in 19th-Century Autralia and New Zealand, but no comprehensive, international consideration of the role of moving panoramas in the history of visual culture. That is, until now: Erkki Huhtamo's Illusions in Motion not only takes up the larger histories of this medium, but documents them with an enormous number of hitherto-unseen primary-source materials. For a medium of which so few actual examples survive -- Professor Huhtamo's annotated list at the end of the book catalogs the two dozen or so known -- they left behind a vast array of supportive and descriptive materials, ranging from handbills and programmes to newspaper adverts, engravings, and sketches. Their great heyday happily coincided with that of print, and so perhaps this is to be expected -- but the problem has been that so many of these materials are classed as ephemera and poorly or incompletely collected or catalogued, that it required almost a superhuman effort to assemble them.
In many ways, this has been a collective undertaking, continued for many years by scholars such as Ralph Hyde, Scott Wilcox, and Kevin Avery, along with dedicated independent researchers, curators, and artists, such as Suzanne Wray, Peter Morelli, and Sara Velas. And yet, when all these and others gathered at one of the annual meetings of the International Panorama Council, it was always Professor Huhtamo's presentations to which we all looked forward the most keenly, knowing that they would not only contain thoughtful historical analysis, but all manner of illustrative materials most of us had never seen before.
Huhtamo has gathered a great many of these same materials for this authoritative volume, which includes more than 120 black-and-white illustrations, many of items in his own collections. He has personally examined all of the surviving panoramas, participating in the discovery and restoration of several, including the remarkable Morieux panorama from the Paris Exposition of 1900, and the Grand Moving Panorama of Pilgrim's Progress, which was recently displayed in full in Saco Maine, accompanied by a full-size copy on cloth which was performed with the original narration before rapt audiences. Having been to one of these performances myself, I can report that, when the lights were dimmed, and the narrator and accompanist wove their overlapping spells, the magic worked as well in 2013 as it had in 1851.
As a subject for a book, though, the moving panorama has two daunting aspects: the vast number of them that once were shown, and the great variety of additional techniques and apparati associated with them, many of which are very imperfectly documented, and indifferently named. From the handbills, it's often difficult to tell exactly what, for instance, a "Grand Illustrated Diorama" consisted of -- was it a panorama, a lantern-show, or some combination of the two? Some panoramas touted their use of "mechanical and chemical apparati" without specifying what they were, or used adjectives such as "Dioramic" with no clear indication of what that meant.
Huhtamo begins with one of the great enigmas of this kind: the Marshalls, a family of Scots panoramists who displayed their work in Edinburgh, Glasgow, London, and Dublin, routinely attached the word "peristrephic" -- Greek for "turning around" -- to their shows. This seems to have meant something rather different from any other such productions; at least in the purpose-built structures in Glasgow and Edinburgh, their panoramas were shown on a concave surface, with a subtle, naturalistic motion. The chief of the painted figures were nearly life-size, and there were effects such as ships coming into port or smoke emerging from painted cannons, which must have required technicians behind the scenes. Huhtamo adroitly uses the few bits of eyewitness description, along with surviving illustrations and material evidence, to solve -- as best as it ever can be solved -- this persistent mystery.
In succeeding chapters, he provides comprehensive accounts of the major manifestations of the form: the theatrical panorama, the mid-century panorama craze, the interaction and ambiguity between lantern shows and panoramas, and the final efflorescence of the medium in the late 19th and early 20th century, which saw the Poole brothers taking their "Myriorama" shows to small provincial towns in England in vans with gasoline engines. Along the way, every imaginable subject of panoramas is considered, from depictions of river and ocean travel, vertical mountain ascents, religious didacticism and Biblical subjects, to battles and fortifications. One sees here, for the first time, the deep embeddedness of the moving panorama in the culture of nineteenth-century Europe and America; its procession of sequntial imagery was linked to the deepest narrative (and ideological) sense of 'progress,' both individual and national. And, while historians of the fixed great-circle panorama have always cautioned us that they ought not to be seen merely as the progenitor of the cinema, no such caution is made, or needed here. For the translation of the collective desire for narrative into a time-based sequence of images that the moving panorama provided proved to be the essential step from illustrated but static texts into the narratives of cinema, and later of course television.
I can think of no other single volume which both documents -- with care and precision -- and explains, with such clarity and lively engagement -- this central aspect of the visual culture of the nineteenth century.
Posted by Russell Potter at 1:15 PM 1 comment:
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The Arctic Book Review Archive
Russell Potter
Russell Potter is Professor of English and Media Studies at Rhode Island College. He's written about Hip-hop (Spectacular Vernaculars, 1995) and the history of polar exploration (Arctic Spectacles, 2007), as well as a novel, PYG: The Memoirs of Toby, the Learned Pig. His newest book, Finding Franklin: The Untold Story of a 165-Year Search, was published in 2016 by McGill-Queen's University Press.
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Book review: White, Bret Easton Ellis (2019)
VISIONS OF THE NORTH
Black Graves of Beechey Island
Those Who Dared
The Hurly Burly - Outdoor Swimming Society's autumn adventure
Quill & Quire
Ben Ladouceur, Trish Salah, and Joshua Whitehead named Dayne Ogilvie Prize finalists
Viridarium Novum
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In accordance with US law, the Arctic Book Review would like to disclose that it (generally) is sent free copies of books for review by the publishers. No other favors or gratuities are received (or expected), and our reviewers receive no other compensation for their reviews.


text:
Q: I can't control MovieClip in the stage from AS3 class file I created a symbol (MovieClip) in my fla file and added it to the frame. Then i give it instance name at properties panel: "myMC"
Then tried to control it from my class file in directory: root\Test\MyClass.as
package Test {
    import flash.display.MovieClip;

    public class MyClass extends MovieClip{
        public function MyClass() {
            var myMC:MovieClip = getChildByName("myMC") as MovieClip;
            myMC.gotoAndStop(2);
        }
    }
}

After that, imported the class to fla and tried to run:
import Test.MyClass;
var LaunchMyClass:MyClass = new MyClass();

and get this error,
TypeError: Error #1009: Cannot access a property or method of a null object reference.

at Test::MyClass()
at Test_fla::MainTimeline/frame1()

Note that i'm trying to control a MovieClip already in the stage, not calling it from library.

A: First of all, always post the Errormessages you get with your question. Makes things easier.
But now let's look at your script:

I created a symbol (MovieClip) in my fla file and added it to the
  frame. Then i add it as a child using
  addChild(myMC);

if you put it on the stage and gave the MovieClip an Instancename there's no need to call addChild.
in as3 it's convinient to start classnames with a capital letter, so instead of myClass, call it MyClass.
your package is missing the constructor function, the name for the function has to be the same name as the class' name and the .as filename.
the getChildByName() method expects a String, so you have to wrap myMc in quotes
package  {
    import flash.display.MovieClip;

    public class MyClass extends MovieClip {

        // Constructor
        public function MyClass() {
            // constructor code
            var myMC:MovieClip = getChildByName("myMC") as MovieClip;
            myMC.gotoAndStop(2);
        }
        // End Constructor
    }

}


GO HERE: for one of New York's best—and most unusually located— coffee shops. It's curiously tucked into the tunnels of the Fulton Street subway station. Everything Voyager does, it does with the utmost care—from outfitting the space with dual USB and AC outlets to actually caring about its non-coffee items (e.g., even the rare Alba cinnamon from Particle in Melbourne on the chai is deliberate). The multi-roaster program features beans from Portland's Heart and Vancouver's 49th Parallel (among others), fueling a downtown commuter crowd of devoted regulars.
ORDER THE: elegant filter brews and perfectly calibrated espresso drinks. If you're not much of a coffee-drinker, get excited about the looseleaf Prana chai (imported from Australia) and the silky almond-macadamia nut milk that's made in house. Whatever your beverage, the oatmeal with freshly steamed milk or an avocado toast on crunchy Bien Cuit sourdough far surpasses typical cafe pastry offerings.
THE VIBE IS: a lot warmer than the futuristic spaceship design might suggest. There's never a line, the staff is cheery but not overbearing, and the espresso drinks are served on marble slabs begging you to take it to stay. The small staff, led by Aaron Barnard, delivers Aussie hospitality to commuters and perch-sitters alike, all while bopping along to the newest Kaytranada and Little Dragon tracks and chatting about Carl Sagan.
PRACTICAL STUFF: Skip the maze-like route through the office building, and enter the subway station from the street entrance on John Street near William Street. Descend the stairs, pass by the newsstand hawking lotto tickets, and you'll find Voyager on your right. Voyager is open Monday to Friday from 7:30 a.m. to 5 p.m.


With data gathered over a range of connected operating and environmental conditions, huge information and analytics are essential to both understanding the physical framework layer and empowering better decision. Thus, DMaaS-empowered analytics permit data center administrators to push toward prescient support through condition-based services.
Sailotech provides a variety of simple-to-complex analytics services from basic data management to advanced advisory services, emerging as a partner of choice for enterprises who are seeking deeper insights from the immense data existing in their business as well as external sources.
We deliver business decisions by analyzing the data using data science & decision science techniques and processes. The combination of predictive and prescriptive analytics along with machine learning is employed to derive actions that account for better results.
Business analytics studies data to predict future scenarios and discover patterns based on available data and performance. Marlabs' Analytics practice can support customers' needs throughout the information management lifecycle and help clients decide on the right technologies to employ that align with their business needs build solutions that integrate easily with legacy systems and deliver smart, multi-layered, and real-time analytics for swift and practical decision-making.
Aricent enables its clients to develop analytics-based solutions that help in improving reliability and efficiency of clients' assets, while minimizing failures and maintenance costs. Aricent's asset management solution framework can be leveraged to build analytics-based asset monitoring and management solutions. Our framework uses analytics and big data technologies for collecting, validating and storing the data received from varied sources such as, smart meters, system sensors and other smart devices. The framework enables running descriptive, predictive and prescriptive analytics over the collected data. It also helps generate dashboards, reports and charts that provide insights to address critical business challenges.
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Data analytics is a field which witnesses a continuous revolution. Since data is becoming increasingly valuable with each passing time, it has being now treated with great care and concern. To cope up with the constant changes in the industries and societies as a whole, new tools, techniques, theories and trends and always introduced in the data analytics sector.
In this article, we will go through some of the latest data analytics opportunities which have come up in the industry.
We have witnessed how Big Data and its analysis have reshaped operation of many businesses. Recognizing the facts of big data analytics courses, true scope of data analysis, the sports world making use of analytics. As we speak, the world of sports is improving their capabilities using sports analytics.
I'm convinced that the ingredient for the effective use of data and analytics that is in shortest supply is managers' understanding of what is possible. Data, hardware, and software are available in droves, but human comprehension of the possibilities they enable is much less common. Given that problem, there is a great need for more education on this topic.


8 original modern Jazz melodies presented by one of Philly's unique emerging voices on saxophone with inflections of Neo-Soul, Funk, Latin, R&B, Hip-Hop & Gospel.
"Prehumous", the debut album from Philadelphia saxophonist, Korey Riker, features eight original compositions supported by a cutting-edge ensemble.
Lending their talent are Luke O'Reilly on piano and Fender Rhodes, upright bassist Nimrod Speaks and the first studio recording from Branford Marsalis's new drummer, Justin Faulkner. Riker is also joined by trombonist Ernest Stuart and bassist James Bratten.
Riker's compositional and playing style are greatly influenced by his work in the fields of Neo-Soul, R&B, Gospel & Hip-Hop with artists such as The Roots, John Legend, Mary J Blige, Jill Scott & Erykah Badu. However, don't think that this group held back in the studio! This raw, exposed, upfront performance is played as if they were sweating out the selections live at the club.
What we are left with is an honest record from a honest saxophonist sharing his unique voice in the field. With a well rounded album supported by an all-star group, this record is one worth checking out!


text:
Atlanta Hawks Sign Second-Round Draft Pick Mike Scott
by SLAM Staff September 07, 2012
The Atlanta Hawks have signed second-round draft pick Mike Scott to a two-year, partially-guaranteed contract. Scott, a 6-8 forward from the University of Virginia, earned First Team All-ACC honors as a senior, averaging 18 points and 8 rebounds per game. Via InsideHoops.com: "Scott was selected by Atlanta in the second round (43rd overall) of the 2012 NBA Draft. According to the Atlanta Journal Constitution, 'Scott signed a two-year contract for the minimum salary that includes some guarantees, according to Hawks GM Danny Ferry. The minimum salary for 2012-13 is $473,604. 'Mike will be on the team this year,' Ferry wrote in a text message.' He ranks third University of Virginia history in rebounds (944) and double-doubles (34), while finishing 16th in points scored (1,538). He will wear number 32."
Atlanta Hawks Mike Scott
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Hawks Acquire Chandler Parsons In Trade With Grizzlies
Mike Scott Agrees To Re-Sign With Philadelphia On Two-Year Deal
Hawks To Sign Charlie Brown Jr. To Two-Way Deal
HIGHER WE GO: John Collins Is Up to Something in Atlanta 🛫
Is Cam Reddish the Next Paul George? 🧐 Hawks Got a STEAL!


text:
Top Obstetrics and Gynecology Programs | US Graduate School Rankings | Best Medical Schools in USA
Best Graduate Obstetrics and Gynecology Programs in US 2020
Ranked by US News in 2019, part of Best Medical Schools
RANKINGS OF MEDICAL SCHOOLS: RESEARCH
RANKINGS OF MEDICAL SCHOOLS: PRIMARY CAR
ENROLLMENT (FULL-TIME)
#1 Harvard University Boston, MA #1 #17 $61,600 (full-time) 712
#2 Johns Hopkins University Baltimore, MD #2 #26 $53,400 (full-time) 476
#3 University of California--San Francisco San Francisco, CA #5 #3 $34,977 (in -state, full-time); $47,222 (out-of-state, full-time) 645
#4 University of Pennsylvania (Perelman) Philadelphia, PA #3 #10 $57,884 (full-time) 587
#5 Columbia University New York, NY #6 #39 $61,146 (full-time) 620
#6 University of Michigan--Ann Arbor Ann Arbor, MI #16 #6 $37,540 (in -state, full-time); $56,640 (out-of-state, full-time) 717
#7 Northwestern University (Feinberg) Chicago, IL #19 #35 $59,986 (full-time) 666
#8 Duke University Durham, NC #13 #31 $59,100 (full-time) 503
#8 University of Pittsburgh Pittsburgh, PA #13 #14 $56,004 (in -state, full-time); $58,186 (out-of-state, full-time) 579
#10 Washington University in St. Louis St. Louis, MO #8 #12 $65,044 (full-time) 492
#11 University of North Carolina--Chapel Hill Chapel Hill, NC #23 #1 $30,437 (in -state, full-time); $57,316 (out-of-state, full-time) 788
#12 Brown University (Alpert) Providence, RI #36 #26 $61,244 (full-time) 590
#12 Oregon Health and Science University Portland, OR #29 #6 $42,636 (in -state, full-time); $64,896 (out-of-state, full-time) 602
#12 Yale University New Haven, CT #13 #44 $61,140 (full-time) 391
15 Stanford University
16 Baylor College of Medicine
16 Mayo Clinic School of Medicine (Alix)
16 New York University (Langone)
16 University of California--San Diego
16 University of Texas Southwestern Medical Center
21 University of California--Los Angeles (Geffen)
22 University of Alabama--Birmingham
23 Ohio State University


text:
Editor of Ruth Bader Ginsburg documentary on what makes her a supreme icon
By Jenny McGrath	 January 29, 2018 6:49PM PST
Just what makes Ruth Bader Ginsburg so notorious?
From her workouts to her dissents and sparkly collars, the Supreme Court justice has earned the moniker that lawyer Shana Knizhnik gave her back in 2013, with the Notorious RBG Tumblr. A new documentary about the 84-year-old Ginsburg debuted at the 2018 Sundance Film Festival. Julie Cohen, creator of Court TV's Supreme Court Watch, and Betsy West, a filmmaker and professor at the Columbia School of Journalism, directed the film. Digital Trends spoke with RBG's editor, Carla Gutierrez, about what she thinks viewers will learn about — and from — Ginsburg.
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Perhaps many of Ginsburg's fans who are too young to remember her 1993 confirmation hearing would describe her as a pugnacious little shorty with a 1,000 IQ, à la a certain Smart Guy. What they may not know is that Ginsburg has been fighting against discriminatory laws during her career. In 1972, she first argued before the Supreme Court in the Frontiero v. Richardson case. A female lieutenant in the United States Air Force requested spousal dependency for her husband and was denied, indicating there were different qualification criteria for her than for her male colleagues. The Court ruled in favor of Ginsburg's argument that this was discriminatory, eight to one. "An amazing discovery for me was really learning what the work that was done during the women's movement but on a legal level to fight for women's rights and gender equality," Gutierrez said.
While framed around four cases that highlight Ginsburg's career, the documentary also gives insight into her background and family life. "We're all affected by our intimate experiences," Gutierrez said. "She grew up as a woman in the 1940's, being one of 11 women of a class of 500 students in Harvard Law School. All those personal experiences have really shaped who she is."
Finding her voice
Gutierrez says the directors, producers, researchers, and herself were able to find a trove of footage and images that help tell Ginsburg's story, including material her upbringing in Brooklyn, New York in the 1930's, and from Cornell and Harvard Universities in the 1950's. On top of the images are excerpts from interviews with Ginsburg herself, her children, lawyers she's worked with, childhood friends, and classmates. "There are men in the film but to me it feels a little bit like a film about an amazing woman and about women's rights told through women's voices and made by women," Gutierrez said.
"We use her voice a lot," Gutierrez added. She went through the C-SPAN footage of Ginsburg's confirmation hearing, which lasted four days. "It gets very specific, and senators love to talk a lot," she said. "It was really invaluable for us to take the time to watch everything so that you find the gems. She just had this energy. The way that she defended and explained her thinking and her way of looking at law as really special."
Ginsburg's voice can give context to other images from the Women's Movement era, Gutierrez believes.
"You see the images over and over again, and they're chanting for equality, and it's an equality that a lot of us — it's some sense of equality that we have taken for granted," she said. "Really discovering the work that her and people like her have done in the background, behind those protests, behind the images that you see, it just adds to the appreciation and it also gives you strength for understanding what needs to be done from here on. And it's just the right moment for it."
Because some of the footage can be packed with legalese, directors West and Cohen tried to find ways the non-lawyers in the audience could still follow the arguments. In addition to using graphics of Ginsburg's words, NPR's legal affairs correspondent, Nina Totenberg, also weighs in. "It was a very personal interview, but she has a radio voice that doesn't go away," Gutierrez said of Totenberg. "She's so knowledgeable, and she's so used to explaining some of that legal stuff in the media to people that are not lawyers, so she was great at giving some context to specific cases we were covering."
"One of the segment I enjoyed editing the most was when she first went to the Supreme Court to argue her first case as a lawyer," Gutierrez said. "Hopefully people will feel like they're going with her and feel her nerves." To portray the intimidation of presenting a case before an all-male Court, Gutierrez used black-and-white images of the men's portraits. This was before Sandra Day O'Connor took her seat in 1981 as the first female justice.
Framed around four cases that highlight Ginsburg's career, the documentary also gives insight into her background.
In addition to the historical cases, RBG shows personal photos and old 8mm film of Ginsburg. "There's a part of the film where she talks about her mom and the two lessons she learned from her mom and one of them was never waste your time with emotions that are going to be wasteful, like jealousy and anger. Just keep putting your head down and do the work. That was really inspiring," said Gutierrez.
Part of being an editor is knowing not only what to keep in but what to cut, such as a portion of Ginsburg's nomination speech in the Rose Garden when she mentions her mother, who died when the justice was a teenager.
"It was very emotional, and we had that moment for a long time in the film, but just the way the whole segment was being built, it just did not belong there," said Gutierrez. "Letting go, even though it was such a beautiful moment, it made that whole chunk of the film a lot stronger."
After coming to the U.S. from Peru as a teenager, Gutierrez learned to speak English and eventually enrolled in Stanford University's documentary program.
"I identify myself as an immigrant," she said. "I identify myself really strongly with the U.S. Latino community here."
Gutierrez has been working on films since 2005 and has four films she's worked on come to the Sundance Film Festival; one has been nominated for an Academy Award. She said what draws her to documentaries is "the possibility of intimacy, because I find that the very personal, intimate stories can really build empathy and compassion… I feel like there's a power in documentary storytelling that can really make people open to other people's experiences."
She can't wait until her oldest child sees RBG. (Her youngest isn't yet old enough to appreciate the documentary, she said.) While her two children have grown up with a working mother and a father who splits the work of raising them and running a household, Gutierrez also wants them to understand the history Ginsburg helped shape.
While many have an image of Ginsburg as a progressive voice in the Supreme Court, Gutierrez said the documentary shows how much the justice relies upon precedent.
"She's not an activist judge," Gutierrez said. "She's so strategic and so careful with what she puts on paper. She has an amazing legal mind. I learned by listening to other people explain it how she's setting up precedence for the future in her dissents; so, she's thinking long-term."
When we asked Gutierrez what snack viewers should have on hand when watching RBG, she suggested an everything bagel — a nod to the Brooklyn roots of both Ginsburg and Notorious B.I.G. We also wanted to know what she thinks draws so many generations of women to see the Notorious RBG as a role model.
"You have this older woman that is so sharp and so strong, and you have the image of an older Jewish grandmother that is putting this strength on paper, that is being a really strong voice for defending what she believes in," she said. "Some combination that makes her really special."
This article is part of a series of reports from the 2018 Sundance Film Festival. Digital Trends was a guest of Adobe Premiere Pro during the event.
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